Effect of Six Weeks of Treadmill Running on JAK1/STAT3 Pathway Gene Expression in the Basal Ganglia of Type-1 Diabetic Rats

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Effect of Six Weeks of Treadmill Running on JAK1/STAT3 Pathway Gene Expression in the Basal Ganglia of Type-1 Diabetic Rats

Mozhdeh Barzegaran¹ , Ziya Fallahmohammadi²^ , Abolfazl Akbari³

1. Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran.

2. Corresponding Author,Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran.

3. Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran.

Article Info ABSTRACT

Article type:

Research

Article history:

Received:

16 April 2023 Received in revised form:

24 May 2023 Accepted:

7 June 2023 Published online:

6 June 2023

Keywords:

Basal Ganglia, Endurance Exercise, JAK1/STAT3 Pathway, Type-1 Diabetes.

Introduction: The JAK/STAT signaling pathway is an important pathway used by cytokines and its excessive activation can lead to various diseases.

This signaling pathway is essential for normal homeostasis. Dysregulation of this pathway contributes to the development of obesity and diabetes. This study aimed to investigate the effect of six weeks of endurance running exercises on the gene expression of the JAK1/STAT3 pathway in the basal ganglia of diabetic rats.

Methods: In this experimental study, 40 male rats were randomly divided into four equal Healthy, Exercise, Diabetes, and Diabetes + Exercise groups.

Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). The incremental endurance exercise program was gradually implemented for six weeks, and five sessions per week. The first week started with a speed of 10 m/min for 10 minutes, and by the sixth week, it reached a speed of 18 m/min for 30 minutes. Forty-eight hours after the last exercise session, the rats were anesthetized and the brain tissue was removed from the skull to extract the basal ganglia. The extracted tissue was used to measure gene expression by the qPCR method. One-way ANOVA and LSD post hoc test were used to check the between-group differences. The significance level was considered smaller than 0.05.

Results: Type-1 diabetes induction did not change JAK1/STAT3 gene expression in basal ganglia (P>0.05). The endurance exercise program decreased the gene expression values of JAK1 (P=0.009) and STAT3 (P=0.002) compared to the diabetes group. This decrease had a similar process for both genes.

Conclusion: In the present study, six weeks of endurance running on the treadmill with moderate intensity decreased the gene expression of the JAK1/STAT3 pathway. Therefore, this exercise protocol can be suggested as a non-pharmacological tool without side effects to inhibit this pathway in diabetes to protect basal ganglia neurons.

Cite this article: Barzegaran M., Fallahmohammadi Z., & Akbari A. Effect of Six Weeks of Treadmill Running on JAK1/STAT3 Pathway Gene Expression in the Basal Ganglia of Type-1 Diabetic Rats. Journal of Sport

Biosciences. 2023; 15 (2): 31-43. DOI: https://doi.org/10.22059/jsb.2023.357588.1583

Journal of Sport Biosciences by University of Tehran Press is licensed under CC BY-NC 4.0.

| Web site: https://jsb.ut.ac.ir/ | Email: [email protected].

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ExtendedAbstract

Introduction

Diabetes mellitus is a complex metabolic pathology characterized by hyperglycemia. Hyperglycemia can stimulate the release of many pro-inflammatory cytokines and interferons such as interleukin-6, which causes diabetic complications such as nephropathy, neuropathy, and even impairment in the central nervous system function. It seems that many of these complications were mediated through the stimulation of the JAK/STAT signaling pathway. This pathway transmits chemical information outside the cell to the nucleus and controls the expression of some genes through the transcription process. The binding between the ligand and the receptor causes the transphosphorylation of JAK. JAK then phosphorylates STAT, in the next step STAT is separated from the receptor and regulates the transcription of target genes.

The intracellular JAK-STAT signaling pathway mediates cellular responses to cytokines and growth factors, and its disruption due to the excessive content of cytokines and interferon-gamma in both forms of diabetes causes dysfunction and death of pancreatic beta cells that secrete insulin. The hippocampus and its related areas, including the basal ganglia, are one of the important central areas that play an important role in the occurrence of cognitive behaviors and are also one of the sensitive centers for diabetes damage in the brain. Evidence showed that diabetic-induced disturbance of the JAK/STAT signaling pathway causes neuroinflammatory and cognitive diseases including Parkinson's disease (PD) through the activation and polarization of myeloid cells and T cells topathogenic phenotypes. The increase in the number of microglia and macrophages in diabetes plays an important role in the progression of PD by increasing the activity of this pathway. Therefore, inhibiting the activation of the JAK/STAT pathway can be a promising therapeutic target for the treatment of diabetes-related neurological diseases, including PD.

Recent studies have shown that performing various exercises, including endurance exercises, can inhibit hyperglycemia and improve diabetes complications by increasing glucose consumption in muscles and improving insulin release. Exercise (endurance training) has become an important treatment option for glucose metabolic disorders because it stimulates glucose transporter-4 (Glut4) in skeletal muscle as an insulin-independent adaptive response. Studies have also shown the effect of various exercises, including resistance and long-term moderate and high-volume exercise, on the JAK/STAT pathway in muscle tissue

and testicular tissue. However, despite these results, the consensus about the effects of endurance exercise and its role in the activity of this signaling pathway in the basal gangliatissue is not completely clear. Therefore, the current research aimed to study the effect of endurance treadmill running exercise on the gene expression of JAK1/STAT3 in the basal ganglia of rats with type-1 diabetes.

Methods

In this experimental study, 40 male rats were randomly divided into four equal Healthy, Exercise, Diabetes, and Diabetes + Exercise groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). The incremental endurance exercise program was gradually implemented for six weeks, and five sessions per week.

The first week started with a speed of 10 m/min for 10 minutes, and by the sixth week, it reached a speed of 18 m/min for 30 minutes. Forty-eight hours after the last exercise session, the rats were anesthetized and the brain tissue was removed from the skull to extract the basal ganglia. The extracted tissue was used to measure gene expression by the qPCR method. One-way ANOVA and LSD post hoc test were used to check the between-group differences. The significance level was considered smaller than 0.05.

Results

STZ injection to induce type 1 diabetes did not change JAK1/STAT3 gene expression in basal ganglia (P>0.05). The endurance exercise program decreased the gene expression values of JAK1 (P=0.009) and STAT3 (P=0.002) compared to the diabetes group.

Conclusion

In the present study, six weeks of endurance running on the treadmill with moderate intensity decreased the gene expression of the JAK1/STAT3 pathway.

Therefore, this exercise protocol can be suggested as a non-pharmacological tool without side effects to inhibit this pathway in diabetes to protect basal ganglia neurons

Ethical Considerations

Compliance with ethical guidelines

This research was approved by the ethics committee of the university of Mazandaran with the ethical code of IR.UMZ.REC.1401.096.

Conflict of interest

No conflict of interest is declared.

Acknowledgments

The authors would like to thank Dr. Khadijah Nasiri, who was responsible for measuring gene expression.

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ﺛﺄﺗ ﯿ ﺮ ﺶﺷ ﻪﺘﻔﻫ يور نﺪﯾود نادﺮﮔ راﻮﻧ

ﺮﯿﺴﻣ نژ نﺎﯿﺑ ﺮﺑ JAK1/STAT3

رد هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي شﻮﻣ ﺎﻫ ي ﯽﯾاﺮﺤﺻ

عﻮﻧ ﯽﺘﺑﺎﯾد 1

اﺮﮔزﺮﺑ هدﮋﻣ ن

، 1

ﺪﻤﺤﻣ حﻼﻓ ءﺎﯿﺿ ي

2

، 

يﺮﺒﮐا ﻞﻀﻔﻟاﻮﺑا

3

1 هوﺮﮔ . ﺷزرو يژﻮﻟﻮﯾﺰﯿﻓ ﯽ

، ﺪﮑﺸﻧاد ة ﺷزرو مﻮﻠﻋ ﯽ هﺎﮕﺸﻧاد ، زﺎﻣ نارﺪﻧ ، ﺮﺴﻠﺑﺎﺑ :ﻪﻣﺎﻧﺎﯾار .ناﺮﯾا ،

@gmail.com 20

m.barzegaran.

2 . ﻮﻧ ﯾ ﺪﻨﺴ ة لﻮﺌﺴﻣ ، هوﺮﮔ ﻓﯿ ﺰﯾ ژﻮﻟﻮ ي ﺷزرو ﯽ ، ﺪﮑﺸﻧاد ة ﺷزرو مﻮﻠﻋ ﯽ هﺎﮕﺸﻧاد ، نارﺪﻧزﺎﻣ ، ﺮﺴﻠﺑﺎﺑ :ﻪﻣﺎﻧﺎﯾار .ناﺮﯾا ، [email protected]

- zia

3 . هوﺮﮔ ﯽﺷزرو يژﻮﻟﻮﯾﺰﯿﻓ ،

ﺪﮑﺸﻧاد ة ﺷزرو مﻮﻠﻋ ﯽ هﺎﮕﺸﻧاد ، نارﺪﻧزﺎﻣ ، ﺮﺴﻠﺑﺎﺑ :ﻪﻣﺎﻧﺎﯾار .ناﺮﯾا ، [email protected]

ﻪﻟﺎﻘﻣ تﺎﻋﻼﻃا هﺪﯿﮑﭼ

:ﻪﻟﺎﻘﻣ عﻮﻧ ﯽﺸﻫوﮋﭘ

رﺎﺗ ﯾ ﺦ رد ﯾ ﺖﻓﺎ : 27 / 01 / 1402

ﺦﯾرﺎﺗ ﺑ ﮕﻧزﺎ :يﺮ 03 / 03 / 1402

رﺎﺗ ﯾ ﺦ ﺬﭘ ﯾ شﺮ : 17 / 03 / 1402

رﺎﺗ ﯾ ﺦ رﺎﺸﺘﻧا : 01 / 04 / 1402

ﺪﯿﻠﮐ هژاو :ﺎﻫ ﯽﺘﻣﺎﻘﺘﺳا تﺎﻨﯾﺮﻤﺗ

،

هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي ،

عﻮﻧ ﺖﺑﺎﯾد

، 1 ﺮﯿﺴﻣ JAK/STAT .

:ﻪﻣﺪﻘﻣ ﺮﯿﺴﻣ ﺖﻣﻼﻋ ﻫد ﯽ JAK/STAT ﻦﯾﺎﮐﻮﺘﯾﺎﺳ ﻂﺳﻮﺗ ﻪﮐ ﺖﺳا ﯽﻤﻬﻣ ﺮﯿﺴﻣ

ﯽﻣ هدﺎﻔﺘﺳا ﺎﻫ و دﻮﺷ

لﺎﻌﻓ زﺎﺳ ي ﺑﯿ ﺶ ﺪﺣزا ﯽﻣ نآ ﺪﻧاﻮﺗ يرﺎﻤﯿﺑ ﻪﺑ ﯽﻔﻠﺘﺨﻣ يﺎﻫ ﺮﺠﻨﻣ

.دﻮﺷ ﺮﯿﺴﻣ ﻦﯾا ﻼﻋ ﺖﻣ ﻫد ﯽ ياﺮﺑ ﺳﻮﻤﻫ ﯽﻌﯿﺒﻃ زﺎﺘ

و ﺖﺳا يروﺮﺿ ﻣﺎﮕﻨﻫ

ﯽ ﻪﮐ رد دﻮﺷ ﻢﯿﻈﻨﺗ ﺪﺑ ﮥﻌﺳﻮﺗ

ﯽﻣ ﺖﮐرﺎﺸﻣ ﺖﺑﺎﯾد و ﯽﻗﺎﭼ .ﺪﻨﮐ

زا فﺪﻫ ﻖﯿﻘﺤﺗ ﺎﺣ ﯽﺳرﺮﺑ ﺮﺿ

ﺛﺄﺗ ﯿﺮ ﻪﺘﻔﻫ ﺶﺷ نژ نﺎﯿﺑ يور ﯽﺘﻣﺎﻘﺘﺳا نﺪﯾود ﻦﯾﺮﻤﺗ

ﺮﯿﺴﻣ يﺎﻫ JAK1/STAT3

هﺪﻘﻋ رد هﺪﻋﺎﻗ يﺎﻫ يا

ﻮﻣ ش .دﻮﺑ ﯽﺘﺑﺎﯾد ﯽﯾاﺮﺤﺻ يﺎﻫ

:ﺶﻫوﮋﭘ شور رد

ﻦﯾا ﻖﯿﻘﺤﺗ مﺎﺠﻧا ﯽﺑﺮﺠﺗ شور ﻪﺑ ﻪﮐ ﺖﻓﺮﮔ

40 ﺮﻧ ﯽﯾاﺮﺤﺻ شﻮﻣ ﺮﺳ ﻪﺑ

رﻮﻃ ﻪﺑ ﯽﻓدﺎﺼﺗ

ﻖﯾرﺰﺗ رﺎﺑ ﮏﯾ ﺎﺑ ﺖﺑﺎﯾد .ﺪﻧﺪﺷ ﻢﯿﺴﻘﺗ شزرو+ﺖﺑﺎﯾد و ﺖﺑﺎﯾد ،شزرو ،ﻢﻟﺎﺳ هوﺮﮔ رﺎﻬﭼ ﻞﺧاد

ﺘﭘﺮﺘﺳا ﯽﻗﺎﻔﺻ ﻦﯿﺳﻮﺗوزﻮ

ﻪﺑ ﻣ راﺪﻘ 50 ﻣ ﯿﻠ ﯽ مﺮﮔ / ﺎﻘﻟا نﺪﺑ نزو مﺮﮔﻮﻠﯿﮐ .ﺪﺷ

ﻣﺎﻧﺮﺑ ﮥ ﺮﻤﺗ ﯾﻨ ﯽ ﺘﻣﺎﻘﺘﺳا ﯽ ﻪﺑ ترﻮﺻ رﺪﺗ ﯾ ﺠ ﯽ ﺞﻨﭘ ﻪﺴﻠﺟ د ﻪﺑ ﻪﺘﻔﻫ ر

تﺪﻣ ﺶﺷ .ﺪﺷ اﺮﺟا ﻪﺘﻔﻫ ﮥﺘﻔﻫ

ﺖﻋﺮﺳ ﺎﺑ لوا 10

ﻗد رد ﺮﺘﻣ ﯿ ﻪﻘ تﺪﻣ ﻪﺑ 10 ﻗد ﯿ ﻪﻘ و ﺪﺷ عوﺮﺷ ﺎﺗ

ﮥﺘﻔﻫ ﻢﺸﺷ

ﻪﺑ ﺖﻋﺮﺳ 18 ﻗد رد ﺮﺘﻣ ﯿ ﻪﻘ تﺪﻣ ﻪﺑ 30 ﻗد ﯿ ﻪﻘ ﺳر ﯿﺪ . 48 ﻦﯾﺮﺧآ زا ﺲﭘ ﺖﻋﺎﺳ ﺴﻠﺟ

ﮥ ﯾﺮﻤﺗ ﻦ شﻮﻣ ﺎﻫ ﺑ ﯽ شﻮﻫ و هﺪﺷ

ﺖﻓﺎﺑ يزﺎﺳاﺪﺟ ياﺮﺑ ﺰﻐﻣ هﺪﻘﻋ

ﺎﻫ ي هﺪﻋﺎﻗ ا ي ﺖﻓﺎﺑ .ﺪﺷ جرﺎﺧ ﻪﻤﺠﻤﺟ زا جرﺎﺧ

هﺪﺷ ياﺮﺑ هزاﺪﻧا ﮔﯿ ﺮ ي ﻪﺑ نژ نﺎﯿﺑ

شور هدﺎﻔﺘﺳاqPCR

ﺪﺷ ياﻮﻧآ زا . ﯾ ﻪﻓﺮﻄﮑ ﯽﺒﯿﻘﻌﺗ نﻮﻣزآ و ﻦﯿﺑ توﺎﻔﺗ ﯽﺳرﺮﺑ ياﺮﺑLSD

ﺮﮔ هو ﺎﻫ ﺪﺷ هدﺎﻔﺘﺳا .

ﺢﻄﺳ ﻨﻌﻣ ﺎ راد ي ﮏﭼﻮﮐ ﺮﺗ زا 05 /0 .ﺪﺷ ﻪﺘﻓﺮﮔ ﺮﻈﻧ رد

ﯾ ﻪﺘﻓﺎ ﺎﻫ : يﺎﻘﻟا عﻮﻧ ﺖﺑﺎﯾد 1

نﺎﯿﺑ رد يﺮﯿﯿﻐﺗ نژ

ﺎﻫ ي JAK1/STAT3 هﺪﻘﻋ

ﺎﻫ ي هﺪﻋﺎﻗ ا ي ﻪﺑ دروﺎﯿﻧ دﻮﺟو

) 05 /0 P>

ياﺮﺟا .(

ﻣﺎﻧﺮﺑ ﮥ نﺎﯿﺑ ﺮﯾدﺎﻘﻣ ﺶﻫﺎﮐ ﺐﺟﻮﻣ ﯽﺘﻣﺎﻘﺘﺳا ﯽﺷزرو نژ

ﺎﻫ ي )JAK1 009 /0 (P=

و STAT3

002) /0 P= ( ﺖﺑﺎﯾد هوﺮﮔ ﺎﺑ ﻪﺴﯾﺎﻘﻣ رد ﺪﺷ

ﺑ نژ ود ﺮﻫ ياﺮﺑ ﯽﻬﺑﺎﺸﻣ ﺪﻧور زا ﺶﻫﺎﮐ ﻦﯾا . ﺑ رادرﻮﺧﺮ

ﻮ .د

ﺘﻧ ﯿ ﻪﺠ ﮔﯿ ﺮ ي : رد ﻖﯿﻘﺤﺗ ﺮﺿﺎﺣ ﺶﺷ ﻪﺘﻔﻫ نﺪﯾود ﯽﺘﻣﺎﻘﺘﺳا يور نادﺮﮔ راﻮﻧ ﺎﺑ تﺪﺷ ﻂﺳﻮﺘﻣ ﻣ ﺐﺟﻮ ﺶﻫﺎﮐ نﺎﯿﺑ

نژ ﺎﻫ ي ﺮﯿﺴﻣ JAK1/STAT3 ﺪﺷ

. ﻦﯾازا ور ﻣ ﯽ ناﻮﺗ ﻦﯾا ﻞﮑﺗوﺮﭘ ﯽﺷزرو ار ﻪﺑ ناﻮﻨﻋ ﮏﯾ راﺰﺑا ﯽﯾورادﺮﯿﻏ و

نوﺪﺑ ضراﻮﻋ ﯽﺒﻧﺎﺟ ياﺮﺑ رﺎﻬﻣ ﻦﯾا ﺮﯿﺴﻣ رد يرﺎﻤﯿﺑ ﺖﺑﺎﯾد ياﺮﺑ ﺖﻇﺎﻔﺣ زا ﻧ نورﻮ ﺎﻫ ي هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي دﺎﻬﻨﺸﯿﭘ

دﺮﮐ .

دﺎﻨﺘﺳا : هدﮋﻣ ،ناﺮﮔزﺮﺑ

؛ ءﺎﯿﺿ ،يﺪﻤﺤﻣ حﻼﻓ و ؛

.ﻞﻀﻔﻟاﻮﺑا ،يﺮﺒﮐا ﺛﺄﺗ

ﯿﺮ ﺶﺷ ود ﻪﺘﻔﻫ ﯾ نﺪ ور ي نادﺮﮔ راﻮﻧ ﺑ ﺮﺑ ﯿ نﺎ ﻣ نژ ﺴ ﯿﺮ JAK1/STAT3 رد

هﺪﻘﻋ ﺎﻫ ي

هﺪﻋﺎﻗ ا ي شﻮﻣ ﺎﻫ ي اﺮﺤﺻ ﯽﯾ د ﯾ ﺘﺑﺎ ﯽ عﻮﻧ 1 ﺮﺸﻧ . ﺷزرو ﯽﺘﺴﯾز مﻮﻠﻋ ﯾﮥ ﯽ

. 1400 ؛ 14 ) 2 :(

31-43 .

2023.357588.1583

jsb.

/ 10.22059 https://doi.org/

DOI:

ﺰﻨﻣﺎﮐ ﻮﯿﺘﯾﺮﮐ ﺲﻨﺴﯾﻻ سﺎﺳا ﺮﺑ ار دﻮﺧ يﺮﮑﻓ ﺖﯿﮑﻟﺎﻣ ﻖﺣ و ﺖﺳا نﺎﮕﯾار ،ﯽﻤﻠﻋ ﮥﯾﺮﺸﻧ ﻦﯾا ﻪﺑ ﯽﺳﺮﺘﺳد )

CC BY-NC 4.0 (

.ﺖﺳا هدﺮﮐ راﺬﮔاو نﺎﮔﺪﻨﺴﯾﻮﻧ ﻪﺑ :ﻪﯾﺮﺸﻧ سردآ|

/ https://jsb.ut.ac.ir :ﻞﯿﻤﯾا|

[email protected]

:ﺮﺷﺎﻧ .ناﺮﻬﺗ هﺎﮕﺸﻧاد تارﺎﺸﺘﻧا ﺴﯾﻮﻧ©

.نﺎﮔﺪﻨ

(4)

ﻣ ﻪﻣﺪﻘ

ﺖﺑﺎﯾد سﻮﺘﯿﻠﻣ ﺳآ ﯿ ﺐ ﺳﺎﻨﺷ ﯽ ﮏﯿﻟﻮﺑﺎﺘﻣ هﺪﯿﭽﯿﭘ

و ﯽﻣاﺪﻧاﺪﻨﭼ ﺖﺳا

ﻪﮐ ﺎﺑ ﯽﻤﺴﯿﻠﮔﺮﭙﯿﻫ ﺺﺨﺸﻣ

ﻣ ﯽ دﻮﺷ . ﺪﻫاﻮﺷ رﻮﻬﻇﻮﻧ نﺎﺸﻧ ﯽﻣ ﺪﻫد ﻪﮐ

ﺮﯿﺴﻣ لﺎﻨﮕﯿﺳ ﯽﻫد رﺎﯿﺴﺑ ﺖﻇﺎﻔﺣ هﺪﺷ و يﻮﻗ

STAT1

ياﺮﺑJAK/

زﺎﺘﺳﻮﻤﻫ ﯽﻌﯿﺒﻃ مزﻻ

،ﺖﺳا و ﯽﻧﺎﻣز ﻪﮐ ﻢﯿﻈﻨﺗ

،دﻮﺷ هدز ﻢﻫ ﺮﺑ نآ ﻪﺑ

دﺎﺠﯾا ﺖﺑﺎﯾد نآ ﺎﺑ ﻂﺒﺗﺮﻣ تﻻﻼﺘﺧا و ﮏﻤﮐ

ﯽﻣ ﺪﻨﮐ ) 1

، 2 ( رد . لﺎﺳ ﺎﻫ ي ﺧا ﯿﺮ ﻪﺑ ﻼﺘﺑا ﺮﻄﺧ ، ﺑﯿ

رﺎﻤ ي ﺘﺧﺎﻨﺷ ﯽ ﺐﯾﺮﺨﺗ و ﺪﻨﻨﮐ ة ﯽﺒﺼﻋ داﺮﻓا رد

ﻪﺑ ﻼﺘﺒﻣ ﺖﺑﺎﯾد ور ﺖﺳا ﺶﯾاﺰﻓا ﻪﺑ ،

،لﺎﺣ ﻦﯾا ﺎﺑ رﺎﮐوزﺎﺳ

ﺎﻫ ي ﻟﻮﮑﻟﻮﻣ ﯽ ﻣز ﯿﻨ ﮥ ﺑ ﻞﻣﺎﻌﺗ ﯿ ﻦ ﺎﻬﻧآ ﻪﺑ رﻮﻃ ﻞﻣﺎﮐ ﻪﺘﺧﺎﻨﺷﺎﻧ هﺪﻧﺎﻣ ﺖﺳا ) 3 ، 4 ( رد.

ﻦﯿﮐﻮﻟﺮﺘﻨﯾا ﯽﯾﺎﻫر ﯽﻤﺴﯿﻠﮔﺮﭙﯿﻫ ،ﯽﻫﺎﮕﺸﯾﺎﻣزآ ﻂﯾاﺮﺷ 6

ﮏﯾﺮﺤﺗ ار ﻣ

ﯽ ﺪﻨﮐ ﯽﻓوﺮﺗﺮﭙﯿﻫ و ﺮﯿﺜﮑﺗ ﺐﺟﻮﻣ ﻪﮐ لﻮﻠﺳ

ﺎﻫ ي و رﻻﻮﺑﻮﺗ و لﺎﯾﮋﻧاﺰﻣ

ﺮﯿﺴﻣ ﺖﯾﻮﻘﺗ ﻖﯾﺮﻃ زا ﯽﺘﺑﺎﯾد ﯽﺗﺎﭘوﺮﻔﻧ ﺖﻣﻼﻋ

ﻫد ﯽ JAK/STAT ﻣ

ﯽ دﻮﺷ ) 5 ( گﺮﻣ و يرﺎﮐﺪﺑ ﺖﻠﻋ . لﻮﻠﺳ

ﺎﻫ ي ﺪﻌﻤﻟازﻮﻟ يﺎﺘﺑ ة

ﺢﺷﺮﺗ ﺪﻨﻨﮐ ة ﻟﻮﺴﻧا ﯿ ﻦ ﺖﺳا توﺎﻔﺘﻣ رﺎﯿﺴﺑ

، ﺎﻣا ﺖﻣﻼﻋ ﻫد ﯽ JAK/STAT ﻦﯾا رد

اﺮﻓ ﺪﻨﯾ ﺖﺑﺎﯾد رد .دراد ﺖﮐرﺎﺸﻣ ﺖﺑﺎﯾد ﻞﮑﺷ ود ﺮﻫ رد

عﻮﻧ 1 رﺎﮐوزﺎﺳ ﯽﻨﻤﯾادﻮﺧ يﺎﻫ ﻦﯾا ﺐﯾﺮﺨﺗ ﯽﻠﺻا ﻞﻣﺎﻋ

لﻮﻠﺳ ﺎﻫ گﺮﻣ .ﺪﻨﺘﺴﻫ لﻮﻠﺳ

ﺎﻫ ي نﺎﯿﺑ ﺶﯾاﺰﻓا ﺎﺑ ﺎﻣﺎﮔ نوﺮﻓﺮﺘﻨﯾا زا ﯽﺷﺎﻧ ﺎﺘﺑ

ﺌﺗوﺮﭘ ﯿ ﻦ ﺎﻫ ي ﺶﯿﭘ ﻪﺑ ﻪﺘﺴﺑاو ﯽﺑﺎﻬﺘﻟا لﺎﻌﻓ

زﺎﺳ ي JAK/STAT ) ﺖﺳا هاﺮﻤﻫ

1 ﺮﯿﺴﻣ .(

ﮓﻨﯿﻟﺎﻨﮕﯿﺳ

STAT -

ﺠﻧزJAK

ﯿ هﺮ ا ي زا ﻞﻌﻓ و

تﻻﺎﻌﻔﻧا ﻦﯿﺑ ﺌﺗوﺮﭘ ﯿ ﻦ ﺎﻫ ي ﮏﯾ لﻮﻠﺳ ﺦﺳﺎﭘ ﻪﮐ ﺖﺳا يﺎﻫ

ﯽﻟﻮﻠﺳ ﻪﺑ ﻦﯿﮐﻮﺘﯿﺳ ﺎﻫ و يﺎﻫرﻮﺘﮐﺎﻓ ﺪﺷر

ار ﺖﻃﺎﺳو ﯽﻣ ﺪﻨﮐ . تﺎﻋﻼﻃا ﺮﯿﺴﻣ ﻦﯾا

ﯽﯾﺎﯿﻤﯿﺷ جرﺎﺧ زا لﻮﻠﺳ ار ﻪﺑ ﻪﺘﺴﻫ ﻞﻘﺘﻨﻣ زا ﯽﺧﺮﺑ نﺎﯿﺑ و نژ

ﺎﻫ زا ار ﻖﯾﺮﻃ ﺪﻨﯾاﺮﻓ ﯽﺴﯾﻮﻧور لﺮﺘﻨﮐ

ﻣ ﯽ ﺪﻨﮐ هﺪﻧﺮﯿﮔ و ﺪﻧﺎﮕﯿﻟ ﻦﯿﺑ لﺎﺼﺗا .

ﺲﻧاﺮﺗ ﺐﺟﻮﻣ نﻮﯿﺳﻼﯾرﻮﻔﺴﻓ

ﻣJAK

ﯽ دﻮﺷ . ﺲﭙﺳJAK

ﻪﻠﯾرﻮﻔﺴﻓ ارSTAT

ﻣ ﯽ ﺪﻨﮐ ﻠﺣﺮﻣ رد ، ﮥ ﺪﻌﺑ اﺪﺟ هﺪﻧﺮﯿﮔ زا STAT

ﻣ ﯽ دﻮﺷ و

ﯽﺴﯾﻮﻧور نژ

ﺎﻫ ي ﻢﯿﻈﻨﺗ ار فﺪﻫ ﻣ

ﯽ ﺪﻨﮐ ) 5 (.

ﻦﯿﮐﻮﺘﯿﺳ ﺎﻫ و يﺎﻫرﻮﺘﮐﺎﻓ ﺪﺷر

ﺮﻃ زا ﯾ ﻖ لﺎﻌﻓ زﺎﺳ ي ﺴﻣ ﯿﺮ

JAK/STAT

ﻈﻨﺗ رد ، ﯿ ﻢ ،ﺪﺷر

ﺎﻤﺗ ﯾﺰ لﻮﻠﺳ دﺮﮑﻠﻤﻋ و ﺎﻫ

ي ﻣ ﯿ ﺋﻮﻠ ﯿﺪ ي وﺎﻔﻨﻟ و ي ﻤﻫا زا ﯿ ﺖ قﻮﻓ هدﺎﻌﻟا ا ي ﺪﻧرادرﻮﺧﺮﺑ .

ﺮﯿﺴﻣ

JAK/STAT

شراﺰﮔ هﺪﺷ ﺖﺳا ﻪﮐ ياﺮﺑ

زﺎﺘﺳﻮﻤﻫ ﺖﻓﺎﺑ ﺎﻫ و ماﺪﻧا ﺎﻫ ي ﻒﻠﺘﺨﻣ درﻮﻣ زﺎﯿﻧ ﺖﺳا . لﺎﻨﮕﯿﺳ ﯽﻫد

JAK/STAT

ياﺮﺑ ﺪﻨﯾاﺮﻓ

،ﯽﻨﻤﯾا يﺎﻫ يﺪﺷر

و

،ﮏﯿﺗﺎﺘﺳﻮﻤﻫ زا

ﻪﻠﻤﺟ

نﻮﺧ زﺎﺳ ي

، ﺰﯾﺎﻤﺗ و ﺮﯿﺜﮑﺗ لﻮﻠﺳ

ﺎﻫ ي

،ﯽﻨﻤﯾا

،ﻢﯿﺴﻘﺗ ،يراﺪﻬﮕﻧ تﺮﺟﺎﻬﻣ و ﺮﯿﺜﮑﺗ

لﻮﻠﺳ ﺎﻫ ي

،يدﺎﯿﻨﺑ ﺪﺷر ﻧﺎﮔرا ﯿ ﻢﺴ ﺎﻫ و ﺪﺷر ﻏ دﺪ ﯽﻧﺎﺘﺴﭘ

يروﺮﺿ ﺖﺳا ) 6 ( . ﺴﻣ ﯿﺮ

JAK/STAT

اﺮﺑ ي ا عوﺮﺷ ﯾ ﻨﻤ ﯽ ﺗاذ ﯽ ﻈﻨﺗ ، ﯿ ﻢ رﺎﮐوزﺎﺳ ﺎﻫ ي اﯾ ﻨﻤ ﯽ ﺑﺎﺴﺘﮐا ﯽ ﺎﻬﻧ رد و ﯾ ﺖ ندﺮﮐ دوﺪﺤﻣ ﺦﺳﺎﭘ

ﺎﻫ ي

ﺑﺎﻬﺘﻟا ﯽ ا و ﯾ ﻨﻤ ﯽ رد ﺑﯿ رﺎﻤ ي ﺎﻫ ي ﯽﺑﺎﻬﺘﻟا ﯽﺒﺼﻋ ﺣ ﯿﺗﺎ ﯽ ﺖﺳا ) 7 (.

ﮓﻨﯿﻟﺎﻨﮕﯿﺳ ﺮﯿﺴﻣ

JAK/STAT

ﻦﯾا ﺖﯿﻤﻫا تﻻﺎﻘﻣ زا يرﺎﯿﺴﺑ .ﺖﺳا ﻪﺘﺷاﺬﮔ ﺮﯿﺛﺄﺗ نﺎﺴﻧا يرﺎﻤﯿﺑ و ﺖﻣﻼﺳ زا ﺮﯿﺧا كرد ﺮﺑ ًﺎﻘﯿﻤﻋ

رد ار ﺮﯿﺴﻣ ﺧﺪﺑ

ﯿﻤ ﯽ ﺎﻫ و ﺑﯿ رﺎﻤ ي ﺎﻫ ي شراﺰﮔ ﯽﻨﻤﯾا دﻮﺧ هدﺮﮐ

ﺪﻧا لﻼﺘﺧا . رد

لﺎﻨﮕﯿﺳ ﯽﻫد

JAK/STAT

ﻣ ﯽ ﺪﻧاﻮﺗ ﺐﺒﺳ عوﺮﺷ و ﺖﻓﺮﺸﯿﭘ

ﻂﯾاﺮﺷ

،ﮏﯾژﻮﻟﻮﺗﺎﭘ زا

ﻪﻠﻤﺟ ﺮﺳ

،نﺎﻃ ﺑﯿ رﺎﻤ ي ﺎﻫ ي ،ﯽﻨﻤﯾادﻮﺧ ﺑﯿ

رﺎﻤ ي ﺎﻫ ي ﮏﯿﻟﻮﺑﺎﺘﻣ و ﯽﻗﺎﭼ ﺪﻨﻧﺎﻣ

ﺖﺑﺎﯾد و ﺑﯿ رﺎﻤ ي ﺎﻫ ي دﻮﺷ ﯽﺒﺼﻋ )

8 ، 9 ( .

STAT3

ﻠﻏا ﺐ

،ﯽﻨﻤﯾا ﺦﺳﺎﭘ ﯽﻔﻨﻣ ﻢﯿﻈﻨﺗ رد .دراد ﺖﮐرﺎﺸﻣ رﻮﻣﻮﺗ زﺎﺘﺳﺎﺘﻣ و رﻮﻬﻇ و ،لﻮﻠﺳ زﻮﺘﭘﻮﭘآ و ،ﺰﯾﺎﻤﺗ ،ﺪﺷر

STAT3

ﻣ ﯽ ﺪﻧاﻮﺗ ﺰﯾﺎﻤﺗ

لﻮﻠﺳ ﺎﻫ ي رد ار Th17

ﻪﻋﻮﻤﺠﻣ ا ي زا ﺪﻨﯾاﺮﻓ ﺑﺎﺟ و ،نﻮﯿﺳﻼﯾرﻮﻔﺴﻓ ،ﯽﯾﺎﺸﻏ لﺎﺼﺗا ﺮﯿﻈﻧ لﺎﻨﮕﯿﺳ لﺎﻘﺘﻧا يﺎﻫ ﻪ

ﯽﯾﺎﺟ ﻪﺘﺴﻫ ا ي ﻖﯾﺮﻃ زا

ﺧﺮﭼ ﮥ نﻮﯿﺳﻼﯾﻮﺘﯿﻤﻟﺎﭘ -

ﻤﻟﺎﭘد ﺪﻨﮐ ﻢﯿﻈﻨﺗ نﻮﯿﺳﻼﯾﻮﺘﯿ )

10 ( ﻦﯿﻨﭽﻤﻫ .

3

و ﺎﻫژﺎﻓوﺮﮐﺎﻣ رد ار رﻮﻣﻮﺗ ﺎﺑ ﻂﺒﺗﺮﻣ ﯽﻨﻤﯾا بﻮﮐﺮﺳSTAT

لﻮﻠﺳ ﺎﻫ ي

ﻖﺘﺸﻣ ﺮﮔ بﻮﮐﺮﺳ ﺖﯾﻮﻘﺗ ﺪﯿﺋﻮﻠﯿﻣ زا هﺪﺷ

ﻣ ﯽ ﺪﻨﮐ ) 11

، 12 ( نﺪﺷ لﺎﻌﻓ . ﺑﯿ

ﺶ ﺪﺣزا

3

ﻆﻔﺣ ﻖﯾﺮﻃ زاSTAT

لﻮﻠﺳ ﺎﻫ ي ﯽﻧﺎﻃﺮﺳ يدﺎﯿﻨﺑ )

13 (

ﺐﺒﺳ ﮏﯾژﻮﻟﻮﺗﺎﻤﻫ يﺎﻫرﻮﻣﻮﺗ و لﺎﺘﮐرﻮﻠﮐ نﺎﻃﺮﺳ ،ﻪﯾر نﺎﻃﺮﺳ ،ﻪﻨﯿﺳ نﺎﻃﺮﺳ ،ندﺮﮔ و ﺮﺳ يﺎﻫرﻮﻣﻮﺗ رﻮﻬﻇ ﻣ

ﯽ دﻮﺷ ) 14

، 15 ( ؛ نوﺰﻓا ﺮﺑ

ﻦﯾا دﺎﯾز نﺎﯿﺑ

3

وSTAT 6 -

ﻄﺑارIL

ﮥ ﻒﯿﻌﺿ ﺖﯿﺳﺎﺴﺣ ﺎﺑ ﯽﮑﯾدﺰﻧ ﺷ

ﯿﻤ ﯽ ﻧﺎﻣرد ﯽ نﺎﻃﺮﺳ ﺎﻫ ي دراد ﻪﻨﯿﺳ )

16 ( .

رد لﻼﺘﺧا لﺎﻨﮕﯿﺳ

ﯽﻫد

JAK/STAT

ﻖﯾﺮﻃ زا لﺎﻌﻓ

زﺎﺳ ي و نﺪﺷ هﺰﯾرﻼﭘ لﻮﻠﺳ

ﺎﻫ ي ﻣ ﯿ ﺋﻮﻠ ﯿﺪ ي لﻮﻠﺳ و ﺎﻫ ي ﺗﻮﻨﻓ ﻪﺑ T ﯿ ﭗ ﺎﻫ ي

ﺑﯿ رﺎﻤ ي از،

زوﺮﺑ ﺐﺒﺳ ﺑﯿ

رﺎﻤ ي ﺎﻫ ي ﺑﺎﻬﺘﻟا ﯽ ﺒﺼﻋ ﯽ و ﺘﺧﺎﻨﺷ ﯽ ) نﻮﺴﻨﯿﮐرﺎﭘ يرﺎﻤﯿﺑ ﻪﻠﻤﺟ زا (PD

ﻣ ﯽ دﻮﺷ ) 7

، 17 ( . ﮏﯾ نﻮﺴﻨﯿﮐرﺎﭘ يرﺎﻤﯿﺑ

ﻪﺑ ﻪﮐ ﺖﺳا ﻦﺳ ﻪﺑ ﻪﺘﺴﺑاو يرﺎﻤﯿﺑ دﺮﮑﻠﻤﻋ رد لﻼﺘﺧا ﻞﯿﻟد

نورﻮﻧ ﺎﻫ ي رد ﻦﯿﺌﻠﮐﻮﻨﯿﺳﺎﻔﻟآ ﯽﮔدرﻮﺧﺎﺗﺪﺑ و ﻊﻤﺠﺗ و ﮏﯾژﺮﻨﯿﻣﺎﭘود هﺪﻘﻋ

ﺎﻫ ي

هﺪﻋﺎﻗ ا ي رﻮﻬﻇ ﺰﻐﻣ ﻣ

ﯽ ﺪﻨﮐ ) 18 ( . ﺶﻫوﮋﭘ يﺎﻫ نﺎﺸﻧ ﺮﯿﺧا هداد

ﺪﻧا ﺎﺑ ﻦﯿﺌﻠﮐﻮﻨﯿﺳﺎﻔﻟآ رﺎﺠﻨﻫﺎﻧ نﺎﯿﺑ ﻪﮐ لﺎﻌﻓ

زﺎﺳ ي ﺮﯿﺴﻣ

JAK/STAT

ﻣ ﯽ ﺪﻧاﻮﺗ ﮐ لﺎﻌﻓ ار ﺎﻫژﺎﻓوﺮﮐﺎﻣ و ﺎﯿﻠﮔوﺮﮑﯿﻣ ﺪﻨ

يرﺎﮐﺪﺑ ﻪﺑ و ﺦﺳﺎﭘ

ﺎﻫ ي ﺪﯿﻟﻮﺗ و ﯽﺑﺎﺴﺘﮐا و ﯽﺗاذ ﯽﻨﻤﯾا ﻪﻄﺳاو

ﺎﻫ ي ﺶﯿﭘ ﻪﺠﯿﺘﻧ رد و ﯽﺑﺎﻬﺘﻟا

1. Janus kinase/signal transducer and activator of transcription pathway

(5)

ﺛﺄﺗ ﯿ ﺮ ﻪﺘﻔﻫ ﺶﺷ يور نﺪﯾود

نادﺮﮔ راﻮﻧ ﺮﯿﺴﻣ نژ نﺎﯿﺑ ﺮﺑ

JAK1/STAT3 رد

هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي شﻮﻣ ﺎﻫ ي ...

7

دﻮﺷ ﺮﺠﻨﻣ ﯽﺒﺼﻋ ﻞﯿﻠﺤﺗ )

22 - 19 ( ﺖﻓﺮﺸﯿﭘ رد ﯽﻤﻬﻣ ﺶﻘﻧ ﺎﻫژﺎﻓوﺮﮐﺎﻣ و ﺎﯿﻠﮔوﺮﮑﯿﻣ داﺪﻌﺗ ﺶﯾاﺰﻓا . ﺎﻔﯾا PD

ﻣ ﯽ ﺪﻨﮐ ) 23 ( . ازا ﯾ ﻦ ور رﺎﻬﻣ

ﺮﯿﺴﻣ لﺎﻌﻓ ﺪﺷ ة

JAK/STAT

ﻣ ﯽ ﺪﻧاﻮﺗ ﯽﻧﺎﻣرد فﺪﻫ ﮏﯾ ﻮﻧ

ﯾ ﺶﺨﺑﺪ ياﺮﺑ يرﺎﻤﯿﺑ نﺎﻣرد يﺎﻫ

نﻮﺴﻨﯿﮐرﺎﭘ ﻪﻠﻤﺟ زا ﺖﺑﺎﯾد ﺎﺑ ﻂﺒﺗﺮﻣ ﯽﺒﺼﻋ

ﺪﺷﺎﺑ ) 24

، 25 ( هﺪﻨﻨﮐرﺎﻬﻣ زا يرﺎﯿﺴﺑ ،ﺮﺿﺎﺣ لﺎﺣ رد . يﺎﻫ

ﯽﯾارﺎﮐ ﻪﺑ ﯽﻨﯿﻟﺎﺑ ﺰﮐاﺮﻣ رد JAK

ﺖﺳد ﯾ ﻪﺘﻓﺎ ﺪﻧا لﺎﺣ رد يﺮﺘﺸﯿﺑ يﺎﻫوراد و ،

لﺎﺣ رد ﺮﺿﺎﺣ ﯽﺳرﺮﺑ

ﺖﺳا ) 26 ( رﺎﻬﻣ ﻦﯾاﺮﺑﺎﻨﺑ . ﺴﻣ

ﯿﺮ

JAK/STAT

ﻣ ﯽ ﺪﻧاﻮﺗ ﯾ ﮏ ﻧﺎﻣرد فﺪﻫ ﯽ

نﺎﻣرد ياﺮﺑ ﺑﯿ

رﺎﻤ ي ﻫﺎ ي ﻒﻠﺘﺨﻣ زا

ﺑﯿ رﺎﻤ ي ﺎﻫ ي ادﻮﺧ ﯾ ﻨﻤ ﯽ ﺎﻫرﻮﻣﻮﺗ و ي ﺎﻣ و ﺪﻣﺎﺟ ﯾﻊ ﺪﺷﺎﺑ ) 27

، 28 ( .

ﺶﻫوﮋﭘ يﺎﻫ نﺎﺸﻧ ﺮﯿﺧا هداد

ﺪﻧا ﯽﺘﻣﺎﻘﺘﺳا تﺎﻨﯾﺮﻤﺗ ﻪﻠﻤﺟ زا ﻒﻠﺘﺨﻣ ﯽﺷزرو تﺎﻨﯾﺮﻤﺗ مﺎﺠﻧا ﻪﮐ ﻣ

ﯽ ﺪﻧاﻮﺗ فﺮﺼﻣ ﺶﯾاﺰﻓا ﻖﯾﺮﻃ زا

ﮔ دﻮﺷ ﺖﺑﺎﯾد ضراﻮﻋ دﻮﺒﻬﺑ و ﯽﻤﺴﯾﻼﮔﺮﭙﯾﺎﻫ رﺎﻬﻣ ﺐﺒﺳ ﻦﯿﻟﻮﺴﻧا يزﺎﺳﺎﻫر دﻮﺒﻬﺑ و تﻼﻀﻋ ﻂﺳﻮﺗ ﺰﮐﻮﻠ )

29 ( (ﯽﺘﻣﺎﻘﺘﺳا تﺎﻨﯾﺮﻤﺗ) شزرو .

ﻪﺑ ﻨﯾﺰﮔ ﮥ ﯽﻧﺎﻣرد ﻤﻬﻣ ﯽ ياﺮﺑ تﻻﻼﺘﺧا ﮏﯿﻟﻮﺑﺎﺘﻣ

ﺰﮐﻮﻠﮔ ﻞﯾﺪﺒﺗ هﺪﺷ ﺖﺳا

، اﺮﯾز ﻞﻗﺎﻧ ﺰﮐﻮﻠﮔ 4 تﻮﻠﮔ) 4(

ار رد ﻠﻀﻋ ﮥ ﺘﻠﮑﺳا ﯽ ﻪﺑ ناﻮﻨﻋ ﮏﯾ

ﺦﺳﺎﭘ ﯽﻘﯿﺒﻄﺗ ﻞﻘﺘﺴﻣ زا ﻦﯿﻟﻮﺴﻧا ﮏﯾﺮﺤﺗ ﻣ ﯽ ﺪﻨﮐ ) 30 ، 31 (.

ﻘﯿﻘﺤﺗ ﻦﯿﻨﭽﻤﻫ تﺎ ﺛﺄﺗ

ﯿﺮ شزرو و ﯽﺘﻣوﺎﻘﻣ ﻪﻠﻤﺟ زا ﯽﺷزرو ﻒﻠﺘﺨﻣ تﺎﻨﯾﺮﻤﺗ

ﻧﻻﻮﻃ ﯽ تﺪﻣ ﺎﺑ ﻢﺠﺣ ﻂﺳﻮﺘﻣ و ﺮﺑ ار ﻻﺎﺑ ﺴﻣ

ﯿﺮ

JAK/STAT

رد ﺖﻓﺎﺑ ﺎﻫ ي نﺎﺸﻧ ﻪﻀﯿﺑ ﺖﻓﺎﺑ و ﻪﻠﻀﻋ هداد

ﺪﻧا ) 32

، 33 ( ﺞﯾﺎﺘﻧ ﻪﺘﺒﻟا .

ﺶﻟﺎﭼ ﮕﻧاﺮﺑ ﯿﺰ ) نارﺎﮑﻤﻫ و يﺮﻧﺮﺗ .ﺖﺳا هدﻮﺑ 2011

( ﺛﺄﺗ ﯿﺮ ﻦﯿﮐﻮﻟﺮﺘﻨﯾا يور ﯽﺘﻣوﺎﻘﻣ تﺎﻨﯾﺮﻤﺗ 6

و JAK/STAT رد ار

ناﻮﺟ نادﺮﻣ

ﺪﻧدﺮﮐ ﯽﺳرﺮﺑ ﯾﺎﺘﻧ .

ﺞ ﻣﺎﻧﺮﺑ ﻦﯾا ﻪﮐ داد نﺎﺸﻧ ﺎﻬﻧآ ﮥ

ﯽﺷزرو تﺎﻨﯾﺮﻤﺗ ﺛﺄﺗ

ﯿﺮ ي يور ﺖﻣﻼﻋ ﻫد ﯽ ﺮﯿﺴﻣ ﯾ هﺪﺷدﺎ نﺎﺴﻧا ﯽﺘﻠﮑﺳا تﻼﻀﻋ رد

رد .دراﺪﻧ ﯽﻘﯿﻘﺤﺗ

،ﺮﮕﯾد ) نارﺎﮑﻤﻫ و اﺮﯾو 2019

ﺮﯿﺴﻣ ﺖﮐرﺎﺸﻣ ﺮﺑ يزاﻮﻫ تﺎﻨﯾﺮﻤﺗ رﺎﺛآ ( ﺖﻣﻼﻋ

ﻫد ﯽ SOCS-JAK-STAT رد

ﻪﺒﻨﺟ ﺎﻫ ي ﻢﺳآ ﯽﻟﻮﮑﻟﻮﻣ ﺪﻧدﺮﮐ ﯽﺳرﺮﺑ

ﺎﻬﻧآ ﺞﯾﺎﺘﻧ . نﺎﺸﻧ

ﻞﯾﺪﻌﺗ ﺎﺑ يزاﻮﻫ تﺎﻨﯾﺮﻤﺗ داد ﺖﻣﻼﻋ

ﻫد ﻢﺳآ رﺎﻬﻣ ﺐﺟﻮﻣ رﻮﮐﺬﻣ ﯽ ﻣ

ﯽ دﻮﺷ ﺎﺑ . ﻪﮑﻧآ

ﺮﯿﺴﻣ ﻦﯾا تاﺮﯿﯿﻐﺗ ﺖﻣﻼﻋ

ﻫد رد ﯽ ﺖﻓﺎﺑ ﺎﻫ ﺮﮕﯾد ي هﺪﺷ ﯽﺳرﺮﺑ لﺎﺣ ﻦﯾا ﺎﺑ ،ﺖﺳا

ﺛﺄﺗ ﯿﺮ و ﺰﻐﻣ ﺖﻓﺎﺑ ﺮﺑ ﯽﺘﻣﺎﻘﺘﺳا تﺎﻨﯾﺮﻤﺗ ﻪﺑ

رﻮﻃ ﯽﺻﺎﺼﺘﺧا

ﻪﺑ رﻮﻃ ﻦﯾاﺮﺑﺎﻨﺑ .ﺖﺳا هﺪﻧﺎﻣ ﻪﺘﺧﺎﻨﺷﺎﻧ ﻞﻣﺎﮐ ﺮﺿﺎﺣ ﻖﯿﻘﺤﺗ زا فﺪﻫ

ﯽﺳرﺮﺑ ﺛﺄﺗ ﯿﺮ نﺪﯾود ﯽﺘﻣﺎﻘﺘﺳا ﯽﺷزرو ﻦﯾﺮﻤﺗ

يور نادﺮﮔ راﻮﻧ نﺎﯿﺑ ﺮﺑ

نژ ﺎﻫ ي

JAK1/STAT3

شﻮﻣ ﺎﻫ ي عﻮﻧ ﺖﺑﺎﯾد ﻪﺑ ﻼﺘﺒﻣ ﯽﯾاﺮﺤﺻ 1

.دﻮﺑ

شور ﺳﺎﻨﺷ ﯽ

ﻪﻌﻟﺎﻄﻣ ﯽﺣاﺮﻃ و تﺎﻧاﻮﯿﺣ

رد ﻦﯾا ﺶﻫوﮋﭘ ﯽﺑﺮﺠﺗ ، 40 اﺮﺤﺻ شﻮﻣ ﺮﺳ ﯾ

ﯽ و داﮋﻧ ﻎﻟﺎﺑ ﺮﻧ ﯾ

رﺎﺘﺴ ﺑ ﻪ رﻮﻃ ﻓدﺎﺼﺗ ﯽ ﻪﺑ رﺎﻬﭼ هوﺮﮔ ) 10 ﻞﻣﺎﺷ (ﯽﯾﺎﺗ 1.

هوﺮﮔ ﺎﻫ ي لﺮﺘﻨﮐ

ﻢﻟﺎﺳ

، 2.

ﻢﻟﺎﺳ ﯽﺷزرو

، 3.

ﺖﺑﺎﯾد لﺮﺘﻨﮐ و

4.

.ﺪﻧﺪﺷ ﻢﯿﺴﻘﺗ ﺖﺑﺎﯾد ﯽﺷزرو شﻮﻣ

ﺎﻫ ي ﻂﯿﺤﻣ رد ﯽﯾاﺮﺤﺻ لﺮﺘﻨﮐ

هﺪﺷ يﺎﻣد ﺎﺑ 22 - 24 ﻪﺟرد

ﺧﺮﭼ و ﮥ ﯽﮑﯾرﺎﺗ ﯽﯾﺎﻨﺷور 12

يراﺪﻬﮕﻧ ﻪﺘﻋﺎﺳ ﻣ

ﯽ ﺪﻧﺪﺷ اﺬﻏ . ي نﺎﮔﺪﻧﻮﺟ اﯾ ﻦ

،ﺶﻫوﮋﭘ ﻟﻮﺗ ﯿﺪ ﺮﺷ ﮐ ﺖ ارﻮﺧ ك ماد روﺮﭙﻬﺑ ﮐ جﺮ دﻮﺑ ﮐ ﻪ ﻪﺑ رﻮﻃ

ﺖﻓﺮﮔ راﺮﻗ تﺎﻧاﻮﯿﺣ رﺎﯿﺘﺧا رد دازآ .

بآ درﻮﻣ ﻧﯿ زﺎ ﺮﻫ ﺣ ﯿ ناﻮ ﻪﺑ ترﻮﺻ دازآ رد ﺮﻄﺑ ي 500 ﻣ ﯿﻠ ﯽ ﻟﯿ ﺮﺘ ي و ﯾ ةﮋ ﺣ ﯿ تﺎﻧاﻮ ﺎﻣزآ ﯾ ﻫﺎﮕﺸ ﯽ رد ﺘﺧا ﯿ رﺎ

راﺮﻗ ﺎﻬﻧآ هداد ﻦﯾا .ﺪﺷ ﻖﯿﻘﺤﺗ ﺘﯿﻤﮐ ﻂﺳﻮﺗ ﮥ

) نارﺪﻧزﺎﻣ هﺎﮕﺸﻧاد قﻼﺧا

IR.UMZ.REC.1401.096

ﺄﺗ (

ﯿﯾ ﺪ ﺷ ﺪ ﺎﺑ ﻖﺑﺎﻄﻣ نآ ﻞﺣاﺮﻣ مﺎﻤﺗ و

ﯿﻧﺎﯿﺑ ﮥ مﺎﺠﻧا ﯽﮑﻨﯿﺴﻠﻫ ﺖﻓﺮﮔ

.

ﻦﯾﺮﻤﺗ ﻞﮑﺗوﺮﭘ

ﻣﺎﻧﺮﺑ ياﺮﺟا ياﺮﺑ ﮥ

اﺪﺘﺑا ﯽﻨﯾﺮﻤﺗ ﻪﺑ

رﻮﻈﻨﻣ ﯽﯾﺎﻨﺷآ و ﻪﺴﻠﺟ ﺞﻨﭘ تﺪﻣ ﻪﺑ تﺎﻧاﻮﯿﺣ ﻪﺑ

ترﻮﺻ تﺪﻣ ﻪﺑ ﻞﯿﻣدﺮﺗ يور ﺮﺑ نﺪﯾود و ﻦﺘﻓر هار 10

-

15 ﺖﻋﺮﺳ ﺎﺑ ﻪﻘﯿﻗد 5

- 10 و ﻪﻘﯿﻗد ﺮﺑ ﺮﺘﻣ ﺷ ﺎﺑ

ﯿ ﺐ ﺮﻔﺻ اﺮﺟا ﺪﺻرد ﺷ

.ﺪ هوﺮﮔ ﺎﻫ ي تﺪﻣ ﻪﺑ ﯽﺷزرو ﺶﺷ

ﻪﺘﻔﻫ ﺮﻫ ﻪﺘﻔﻫ يور ،ﻪﺴﻠﺟ ﺞﻨﭘ

نادﺮﮔ راﻮﻧ تﺪﺷ ﺎﺑ

50 - 55 تﺪﺷ و تﺪﻣ و ﯽﺸﯾاﺰﻓا تاﺮﯿﯿﻐﺗ .ﺪﻨﺘﺧادﺮﭘ ﺖﯿﻟﺎﻌﻓ ﻪﺑ يزاﻮﻫ ﺖﯿﻓﺮﻇ ﺮﺜﮐاﺪﺣ ﺪﺻرد ﻪﺘﻔﻫ

ﺎﻫ ي ﻪﺑ ﯽﻨﯾﺮﻤﺗ

:ﺪﺷ اﺮﺟا ﺮﯾز حﺮﺷ ﮥﺘﻔﻫ

لوا 10 ﺖﻋﺮﺳ ﺎﺑ نﺪﯾود ﻪﻘﯿﻗد 10

؛ﻪﻘﯿﻗد ﺮﺑ ﺮﺘﻣ ﮥﺘﻔﻫ

مود 20 ﺎﺑ نﺪﯾود ﻪﻘﯿﻗد ﺖﻋﺮﺳ

10 ؛ﻪﻘﯿﻗد رد ﺮﺘﻣ ﮥﺘﻔﻫ

مﻮﺳ 30 ﺖﻋﺮﺳ ﺎﺑ نﺪﯾود ﻪﻘﯿﻗد 15

؛ﻪﻘﯿﻗد رد ﺮﺘﻣ ﮥﺘﻔﻫ

مرﺎﻬﭼ 30 ﺖﻋﺮﺳ ﺎﺑ نﺪﯾود ﻪﻘﯿﻗد 15

؛ﻪﻘﯿﻗد رد ﺮﺘﻣ ﮥﺘﻔﻫ

ﻢﺠﻨﭘ 30 نﺪﯾود ﻪﻘﯿﻗد

ﺖﻋﺮﺳ ﺎﺑ 18

و ﻪﻘﯿﻗد رد ﺮﺘﻣ ﮥﺘﻔﻫ

ﻢﺸﺷ 30 ﺖﻋﺮﺳ ﺎﺑ نﺪﯾود ﻪﻘﯿﻗد 18

ﻪﻘﯿﻗد رد ﺮﺘﻣ )

34 ( .

(6)

ﺎﻘﻟا ي ﺖﺑﺎﯾد

دﯾ ﺘﺑﺎ ﯽ ندﺮﮐ شﻮﻣ ﺎﻫ ي ﯽﯾاﺮﺤﺻ زا ﺲﭘ

12 ﯽﻃ و ﯽﯾﺎﺘﺷﺎﻧ ﺖﻋﺎﺳ ﯾ

ﮏ ﺑرﺎ ﻖﯾرﺰﺗ

mg/kg

50 ﻦﯿﺳﻮﺗوزﻮﺘﭘﺮﺘﺳا ﻣ1

رد لﻮﻠﺤ تاﺮﺘﯿﺳ ﺮﻓﺎﺑ

5/

0 ﻪﺘﯾﺪﯿﺳا ﺎﺑ ﺮﺘﯿﻟ رد رﻻﻮﻣ 5

= )5 (pH

و ﻪﺑ ترﻮﺻ نورد ﻗﺎﻔﺻ ﯽ مﺎﺠﻧا ﺖﻓﺮﮔ . زا ﺲﭘ 48 مد زا ﺖﻋﺎﺳ شﻮﻣ

ﺎﻫ ي ﯽﯾاﺮﺤﺻ نﻮﺧ

ﮔﯿ ﺮ ي

ﻪﺑ ﻞﻤﻋ و ﺪﻣآ نﻮﺧ ﺰﮐﻮﻠﮔ ﺖﻈﻠﻏ ﺖﺴﺗ هﺎﮕﺘﺳد ﻂﺳﻮﺗ

نﻮﺧ ﺪﻨﻗ ﮏﭼ ﻮﯿﮐا

هزاﺪﻧا2

ﮔﯿ ﺮ ي ﺪﺷ . ﯽﺗﺎﻧاﻮﯿﺣ ﺰﮐﻮﻠﮔ ﺖﻈﻠﻏ ﻪﮐ نﺎﺸﻧﻮﺧ

زا ﺮﺗﻻﺎﺑ

mg/dl

300 دﻮﺑ ﻪﺑ ناﻮﻨﻋ ﯽﯾﺎﺳﺎﻨﺷ ﯽﺘﺑﺎﯾد ﺪﻧﺪﺷ

) 35 (.

ﻪﻧﻮﻤﻧ رادﺮﺑ ي

ياﺮﺑ ﻊﻤﺟ روآ ي ﻪﻧﻮﻤﻧ مﺎﻤﺗ ﺎﻫ هوﺮﮔ ﺎﻫ ﺎﺑ اﺮﺷ ﯾ ﻂ ﮐ

ًﻼﻣﺎ ﻪﺑﺎﺸﻣ و رد اﺮﺷ ﯾ ﻪﯾﺎﭘ ﻂ ﺎﺑ رﺰﺗ ﯾ ﻖ ﺧاد ﻞ ﻗﺎﻔﺻ ﯽ ﺮﺗ ﯿﮐ ﺒ ﯽ زا ﮐ ﻣﺎﺘ ﯿ ﻦ

3 )

mg/kg

30 - 50 ( و

ازﯾ زﻼ ﯾ ﻦ )4

mg/kg

3 - 5 ( ﺑ ﯽ شﻮﻫ ﺪﻧﺪﺷ . تﺎﻧاﻮﯿﺣ ﺮﺳ ﺲﭙﺳ زا

ﯿﺣﺎﻧ ﮥ ندﺮﮔ ﻂﺳﻮﺗ ﯽﭽﯿﻗ صﻮﺼﺨﻣ اﺪﺟ

.ﺪﺷ اﺪﺘﺑا ﺎﺑ هدﺎﻔﺘﺳا زا ﻎﯿﺗ

ﯽﺣاﺮﺟ ﻪﻤﺠﻤﺟ ﺪﺷ ﻪﺘﻓﺎﮑﺷ و

ﺎﺑ طﺎﯿﺘﺣا ﺰﻐﻣ جرﺎﺧ ﺪﺷ . ﺰﻐﻣ ﻢﻟﺎﺳ ﺎﺑ ﻎﯿﺗ ﯽﺣاﺮﺟ

ًﺎﻘﯿﻗد زا ﻂﺳو ﻪﺑ ود ﻢﯿﻧ ﻢﯿﺴﻘﺗ هﺪﺷ و ﺎﺑ ﻪﺟﻮﺗ ﻪﺑ تﺎﺼﺘﺨﻣ

هﺪﻘﻋ هﺪﻋﺎﻗ يﺎﻫ ﺰﻐﻣ يا

ﻪﺑ ﮏﻤﮐ ﺲﻠﻃا

،سﻮﻨﯿﺴﮐﺎﭘ هﺪﻘﻋ

هﺪﻋﺎﻗ يﺎﻫ ﺰﻐﻣ يا

ﯽﻣاﺪﻗ (ﺎﻤﮔﺮﺑ ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ) تﺎﺼﺘﺨﻣ ﺎﺑ -

= ﯽﻔﻠﺧ 4 - ﻣ ﯿﻠ ﯽ ﺮﺘﻣ ،

= ﯽﺒﻧﺎﺟ 6/

1 + ﻣﯿ ﻠ ﯽ ﺮﺘﻣ ﯽﺘﺸﭘ و ، = ﯽﻤﮑﺷ–

8/

8 ﻣ– ﯿﻠ ﯽ ﺮﺘﻣ اﺪﺟ ﻪﻤﺠﻤﺟ ﺢﻄﺳ زا ﻪﻠﺻﺎﻓﻼﺑ .ﺪﺷ

ﻪﻧﻮﻤﻧ ﺎﻫ ﺎﺑ نژوﺮﺘﯿﻧ ﻊﯾﺎﻣ ﺪﻤﺠﻨﻣ ﺪﺷ و

رد ﺮﻓ ﯾ رﺰ ﺎﺑ ﺎﻣد ي 80 - ﺟرد ﮥ ﺘﻧﺎﺳ ﯽ داﺮﮔ راﺪﻬﮕﻧ ي و اﺮﺑ ي هزاﺪﻧا ﮔﯿ ﺮ ي ﻣ ﯿ ناﺰ نﺎﯿﺑ نژ ﺎﻫ ي

JAK/STAT

ﻪﺑ ﺎﻣزآ ﯾ هﺎﮕﺸ هدﺎﺘﺳﺮﻓ ﺪﺷ .

نژ نﺎﯿﺑ ﯽﺑﺎﯾزرا

نﺎﯿﺑ نژ ﺎﻫ ي

JAK/STAT

ﺖﻓﺎﺑ رد هﺪﻘﻋ ﺎﻫ ي ﺎﭘ ﯾﻪ ا ي ﯽﺳرﺮﺑ ﺪﺷ . ﯽﻟاﻮﺗ يﺎﻫﺮﻤﯾاﺮﭘ درﻮﻣ

هدﺎﻔﺘﺳا رد ﻦﯾا ﻖﯿﻘﺤﺗ رد لوﺪﺟ 1 ﻪﺋارا هﺪﺷ

ﺖﺳا . ﻞﮐ RNA

ﺎﺑ لوﺰﯾﺮﺗ فﺮﻌﻣ ﻖﺑﺎﻄﻣ

ﻞﻤﻌﻟارﻮﺘﺳد (ناﺮﯾا ﺪﻬﺸﻣ ﺖﺴﯾزﺎﻧد) هﺪﻧزﺎﺳ ﺖﮐﺮﺷ

جاﺮﺨﺘﺳا ﺪﺷ . ﺰﺘﻨﺳ زا هدﺎﻔﺘﺳا ﺎﺑ cDNA

ﺖﯿﮐ ﺎﻣزآﺰﯿﻬﺠﺗ ﺎﺘﮑﯾ ﺖﻓﺮﮔ ترﻮﺻ ﺖﮐﺮﺷ ﻞﻤﻋ رﻮﺘﺳد ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ و (ناﺮﯾا)

. ﺶﻨﮐاو ﺠﻧز ﯿ هﺮ ا ي ياﺮﺑ زاﺮﻤﯿﻠﭘ ﻪﻧﻮﻤﻧ

ﺎﻫ ي ياﺮﺑ cDNA

نژ ﺎﻫ ي

3

،STAT

1

ﻧﺮﻓر نژ وJAK

ﺲ

Actin β-

ﺖﮐﺮﺷ ﻦﯾﺮﮔﺮﺒﯾﺎﺳ ﺖﯿﮐ زا هدﺎﻔﺘﺳا ﺎﺑ نﻮﮑﯿﻠﭙﻣا

) كرﺎﻤﻧاد هﺎﮕﺘﺳد رد (

Rotor gene

6000 Corbett

مﺎﺠﻧا ﺖﻓﺮﮔ . نﺎﯿﺑ ناﺰﯿﻣ نژ

ﺎﻫ ي ﺮﻈﻧدرﻮﻣ ) كاﻮﯿﻟ شور ﺎﺑ

ΔΔCT

2-

ﺷ ﻪﺒﺳﺎﺤﻣ ( .ﺪ

لوﺪﺟ 1 . رد هدﺎﻔﺘﺳا درﻮﻣ يﺎﻫﺮﮔزﺎﻏآ ﺪﻨﯾاﺮﻓ

نژ نﺎﯿﺑ ﯽﺑﺎﯾزرا

نژ مﺎﻧ ﯽﻟاﻮﺗ ﯽﺳﺮﺘﺳد ةرﺎﻤﺷ لﻮﺼﺤﻣ لﻮﻃ

(زﺎﺑ ﺖﻔﺟ)

STAT3 F-5'-AAAAGGACATCAGTGGCAAGA-3' R-5'-GTAGAGGTAGACCAGTGGGGATA-3'

NM_012747.2 149

JAK1 F-5'- TCTGCCACAACCTCTTCGC-3' R-5'- TCATAGCCATTTTTCTGCTTCTTT-3'

NM_053466.1 199

β-Actin F-5'-GTGTGACGTTGACATCCGTAAAGAC-3' R-5'-TGCTAGGAGCCAGGGCAGTAAT-3'

NM_031144.3 119

1. Streptozotocin (STZ)

2. ACCU-CHEC Active

3. Ketamine

4. Xylazine

(7)

JAK1/STAT3 رد

9

يرﺎﻣآ ﺰﯿﻟﺎﻧآ

ا رد ﯾ ﺶﻫوﮋﭘ ﻦ زا ﺲﭘ

ﻊﻤﺟ روآ ي هداد ﺎﻫ ي ،مﺎﺧ ﻪﺑ رﻮﻈﻨﻣ ﺳرﺮﺑ ﯽ توﺎﻔﺗ ﺎﻫ ي دﻮﺟﻮﻣ ﻦﯿﺑ هوﺮﮔ ﺎﻫ زا آ ﻟﺎﻧ ﯿ راو ﺰ ﯾ ﺲﻧﺎ ) ﻪﻓﺮﻄﮑﯾ

One-Way

ANOVA

( ترﻮﺻ رد و ﻨﻌﻣ

ﺎ راد نﻮﻣزآ ندﻮﺑ ﻼﺘﺧا هﺪﻫﺎﺸﻣ و F

نﻮﻣزآ زا ف ﯽﺒﯿﻘﻌﺗ

هدﺎﻔﺘﺳا LSD

ﺪﺷ . ا رد ﯾ ﺳرﺮﺑ ﻦ ﯽ ﺢﻄﺳ ﺎﻨﻌﻣ راد ي

ﺮﺘﻤﮐ زا 05 /0 دﻮﺑ ﺮﻔﺻ ضﺮﻓ در يﺎﻨﻌﻣ ﻪﺑ .

زا مﺮﻧ راﺰﻓا ﺨﺴﻧ ﺪﭘ فاﺮﮔ ﮥ

6 ياﺮﺑ ﺰﺠﺗ ﯾﻪ ﻠﺤﺗو ﯿ ﻞ .ﺪﺷ هدﺎﻔﺘﺳا يرﺎﻣآ

ﯾ ﻪﺘﻓﺎ ﺎﻫ

ﻒﻟا ( ﯽﺳرﺮﺑ JAK1

ﺳرﺮﺑ ﯽ ﺎﻫ نژ نﺎﯿﺑ ﺪﻧداد نﺎﺸﻧ ) ﺖﺷاد دﻮﺟو يرادﺎﻨﻌﻣ توﺎﻔﺗ شزرو و لﺮﺘﻨﮐ هوﺮﮔ ﻦﯿﺑJAK1

002 /0

P≤

و 29 /0 ﻪﺑ .(F=

ﯾد ترﺎﺒﻋ ﺮﮕ

نژ نﺎﯿﺑ ﺶﻫﺎﮐ ﺎﺑ شزرو توﺎﻔﺗ ﺖﺑﺎﯾد و شزرو هوﺮﮔ ﻦﯿﺑ ﻦﯿﻨﭽﻤﻫ .دﻮﺑ هاﺮﻤﻫJAK1

رادﺎﻨﻌﻣ ) ﺪﺷ هﺪﻫﺎﺸﻣ ي 005

/0

P≤

و 98 /2 زا .( F=

،ﺮﮕﯾد يﻮﺳ هداد

ﺎﻫ ﻖﯿﻘﺤﺗ ي نﺎﺸﻧ

ﺪﻨﻫد ﺖﺑﺎﯾد و شزرو+ﺖﺑﺎﯾد هوﺮﮔ ﻦﯿﺑ رادﺎﻨﻌﻣ توﺎﻔﺗ دﻮﺟو ة ﺖﺳا

) 009 /0 و P≤

36 /0 ﻪﺑ .(F=

ترﺎﺒﻋ

د ﻪﺘﻔﻫ ﺶﺷ ياﺮﺟا ،ﺮﮕﯾد يور نﺪﯾو

نادﺮﮔ راﻮﻧ رادﻮﻤﻧ) داد ﺶﻫﺎﮐ ار نآ راﺪﻘﻣ

1 .(

رادﻮﻤﻧ 1 . نژ نﺎﯿﺑ ردJAK1

هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي هوﺮﮔ ﺎﻫ ي ﯽﺳرﺮﺑ درﻮﻣ ﻧﺎﺸﻧ ** و * .

ﮥ ﺶﻫﺎﮐ ﺎﻨﻌﻣ راد نﺎﯿﺑ لﺮﺘﻨﮐ هوﺮﮔ ﺎﺑ ﻪﺴﯾﺎﻘﻣ رد نژ .ﻢﻟﺎﺳ

$

و توﺎﻔﺗ ﮥﻧﺎﺸﻧ$$

ﻨﻌﻣ ﺎ راد .ﺖﺑﺎﯾد لﺮﺘﻨﮐ هوﺮﮔ ﺎﺑ ﻪﺴﯾﺎﻘﻣ رد

(8)

ﺳرﺮﺑ (ب ﯽ

STAT3

نژ نﺎﯿﺑ داد نﺎﺸﻧ ﺞﯾﺎﺘﻧ

STAT3

) ﺖﺷاد رادﺎﻨﻌﻣ توﺎﻔﺗ لﺮﺘﻨﮐ و شزرو هوﺮﮔ ﻦﯿﺑ 0001

/0 وP≤

22 /0 ﺖﺑﺎﯾد و شزرو هوﺮﮔ ﻦﯿﺑ .(F=

ﻪﺑ ﺰﯿﻧ يرادﺎﻨﻌﻣ توﺎﻔﺗ ) ﺪﻣآ ﺖﺳد

0007 /0

P≤

و 53 /3 نﺎﯿﺑ رد ﺮﮕﯾد فﺮﻃ زا .(F=

STAT3

توﺎﻔﺗ لﺮﺘﻨﮐ و ﺖﺑﺎﯾد+شزرو هوﺮﮔ ﻦﯿﺑ

) ﺪﺷ هﺪﻫﺎﺸﻣ يرادﺎﻨﻌﻣ 004

/0

P≤

و 32 /0 ) دﻮﺑ توﺎﻔﺘﻣ ﻢﻫ ﺖﺑﺎﯾد هوﺮﮔ و شزرو+ﺖﺑﺎﯾد هوﺮﮔ ﻦﯿﺑ نژ ﻦﯾا نﺎﯿﺑ .(F=

002 /0

P≤

و 45 / 0

.(F=

ﻪﺑ رﻮﻃ

،ﯽﻠﮐ هداد ﻦﯾا ﯽﻣ نﺎﺸﻧ ﺎﻫ رادﻮﻤﻧ) داد ﺶﻫﺎﮐ ار نژ ﻦﯾا نﺎﯿﺑ راﺪﻘﻣ هﺪﻨﯾاﺰﻓ نﺪﯾود شزرو ﻪﺘﻔﻫ ﺶﺷ ياﺮﺟا ﺪﻨﻫد

2 .(

رادﻮﻤﻧ 2 . نژ نﺎﯿﺑ STAT3 رد هﺪﻘﻋ ﺎﻫ ي ﺎﻗ هﺪﻋ ا ي هوﺮﮔ ﺎﻫ ي ﯽﺳرﺮﺑ درﻮﻣ ﺶﻫﺎﮐ ﮥﻧﺎﺸﻧ ** و * .

ﺎﻨﻌﻣ راد .ﻢﻟﺎﺳ لﺮﺘﻨﮐ هوﺮﮔ ﺎﺑ ﻪﺴﯾﺎﻘﻣ رد نژ نﺎﯿﺑ

و$ ﻧﺎﺸﻧ$$

ﮥ توﺎﻔﺗ ﻨﻌﻣ ﺎ راد .ﺖﺑﺎﯾد لﺮﺘﻨﮐ هوﺮﮔ ﺎﺑ ﻪﺴﯾﺎﻘﻣ رد

و ﺚﺤﺑ ﺘﻧ ﯿ ﻪﺠ ﮔﯿ ﺮ ي

زا فﺪﻫ ﻖﯿﻘﺤﺗ ﺮﺿﺎﺣ ﯽﺳرﺮﺑ ﺛﺄﺗ ﯿﺮ ﺮﻤﺗ ﯾ ﻦ ﺷزرو ﯽ ود ﯾ نﺪ يزاﻮﻫ ور ي نادﺮﮔ راﻮﻧ ﺑ ﺮﺑ

ـﯿ نﺎ نژ ﺎـﻫ ي JAK1/STAT3 هﺪـﻘﻋ رد

ﺎـﻫ ي

هﺪﻋﺎﻗ ا ي شﻮﻣ ﺎﻫ ي اﺮﺤﺻ ﯽﯾ د ﻪﺑ ﻼﺘﺒﻣ ﯾ

ﺖﺑﺎ عﻮﻧ 1 .دﻮﺑ ﺘﻓﺎﯾ ﮥ ﯽﻠﺻا ﺶﻫوﮋﭘ نﺎﺸﻧ ﺮﺿﺎﺣ ـﻣ

ﯽ ﺪـﻫد ياﺮـﺟا ﺶـﺷ نﺪـﯾود ﻦﯾﺮـﻤﺗ ﻪـﺘﻔﻫ

ﺶﯿﭘ يور هﺪﻧور نادﺮﮔ راﻮﻧ

نژ نﺎﯿﺑ ﺶﻫﺎﮐ ﺐﺟﻮﻣ ردJAK1

هﺪﻘﻋ ﺎﻫ ي هﺪﻋﺎﻗ ا ي شﻮﻣ ﺎـﻫ ي ﺎـﺑ ﯽﺘﺑﺎـﯾد نژ نﺎـﯿﺑ ﻦﯿـﻨﭽﻤﻫ .ﺪـﺷSTZ

STAT3

رد ﺪﻘﻋ ه ﺎﻫ ي هﺪﻋﺎﻗ ا ي نآ راﺪﻘﻣ و دﺮﮐ ﺖﯿﻌﺒﺗ ﺪﻧور ﻦﯿﻤﻫ زا ﺖﻓﺎﯾ ﺶﻫﺎﮐ

هﺪﻘﻋ. ﺎﻫ ي هﺪﻋﺎﻗ ا ي زا ﯽﻫوﺮﮔ ﻞﻣﺎﺷ ﻪﺘﺴﻫ

ﺎﻫ ي دﻮﺟﻮﻣ

رد ﺰﻐﻣ ﺪﻧ ﯽﻨﻏ و زا لﻮﻠﺳ ﺎﻫ ي ﻨﯿﻣﺎﭘود ﮏﯾژﺮ ﺘﺴﻫ ﺪﻨ ﻦﯾا گﺮﻣ و لﻮﻠﺳ

ﺎﻫ ﺠﯿﺘﻧ رد ﮥ و ﯽـﺸﯾﺎﺴﮐا سﺮﺘـﺳا ﻞـﻣاﻮﻋ نﻮـﭽﻤﻫ ﯽﻔﻠﺘﺨﻣ ﻞﻣاﻮﻋ

دار ﯾ لﺎﮑ ﺎﻫ ي ﻊﯾﺎﺷ ﺖﺑﺎﯾد رد ﻪﮐ دازآ ﺳا

ﺖ

، ﻣ ﯽ ﺪﻧاﻮﺗ .دﻮﺷ ﺮﺠﻨﻣ نﻮﺴﻨﯿﮐرﺎﭘ يرﺎﻤﯿﺑ ﻪﺑ

ﭘ رد ﻢﻬﻣ تﻼﺧاﺪﻣ زا شزرو ﯿ

ﮕﺸ ﯿﺮ ي و ﮐ د لﺮﺘﻨ ﯾ بﻮﺴﺤﻣ ﺖﺑﺎ ﻣ

ﯽ دﻮﺷ و ﻪﮐ ﺖﺳا ﯽﻠﻣاﻮﻋ زا ﺐﺒﺳ

ﺶﻫﺎﮐ حﻮﻄـﺳ و نﺎـﯿﺑ ﻦﯿﺌﺗوﺮـﭘ

JAK/STAT

و نﻮﺧ رد ﺖﻓﺎﺑ

ﺎﻫ ي نﺪـﺑ رد لﺪـﻣ ﺎـﻫ ي ﯽﻧﺎـﺴﻧا و ﯽﻧاﻮـﯿﺣ ـﻣ

ﯽ دﻮـﺷ . ًﻻﺎـﻤﺘﺣا ﺖـﯿﻟﺎﻌﻓ رﺎﮐوزﺎـﺳ ﺪـﻨﭼ ﻖـﯾﺮﻃ زا شزرو

(9)

JAK1/STAT3 رد

11

JAK/STAT

ﺶﻫﺎﮐ ار ﻣ

ﯽ ﺪﻫد ﻦﯾا زا ﯽﮑﯾ . ﺎﻫرﺎﮐوزﺎﺳ

رﺎﻬﻣ ﺖﻣﻼﻋ ـﻫد ﯽ ﯽـﻣ شزرو .ﺖـﺳا ﻦﯾﺎﮐﻮﺘﯾﺎـﺳ ﻦﯾﺎﮐﻮﺘﯾﺎـﺳ ﺪـﯿﻟﻮﺗ ﺪـﻧاﻮﺗ

يﺎـﻫ

ﺶﯿﭘ ﻦﯿﮐﻮﻟﺮﺘﻨﯾا ﺮﯿﻈﻧ ﯽﺑﺎﻬﺘﻟا 6

و ﺮﯿﺴﻣ ﻪﮐ ار ﺎﻔﻟآTNF JAK/STAT

لﺎﻌﻓ ار ﻣ ﯽ ﺪﻨﻨﮐ ﺪﻫد ﺶﻫﺎﮐ ، )

9

، 36 ( ) نارﺎﮑﻤﻫ و ﻦﯿﻣا . 2021

رد (

ﻘﯿﻘﺤﺗ ﯽ ﺛﺄﺗ ﯿﺮ تﺪﺷ ﺎﺑ شزرو ﻪﺴﻠﺟ ﮏﯾ 60

ﺎﺗ 70 ﻦﯿﮐﻮﻟﺮﺘﻨﯾا يور ﻪﻨﯿﺸﯿﺑ ﺪﺻرد 6

و ﯽﺳرﺮﺑ ار ﺎﻔﻟآTNF

ﺪﻧدﺮﮐ ﺎـﻬﻧآ راﺪﻘﻣ ﻪﮐ ﺪﻨﺘﻓﺎﯾرد و

ﺴﻠﺟ يﺎﻬﺘﻧا رد ﮥ

ﯾﺮﻤﺗ ﻪﺑ ﺖﺒﺴﻧ ﻦ ﭘﯿ

ﺶ نﻮﻣزآ ﻪﺑ رﻮﻃ يﺮﯿﮕﻤﺸﭼ ﻧﺎـﺸﻧ ﺶﻫﺎـﮐ ﻦـﯾا ﻪـﮐ ﺪﻨﺘﻓﺮﮔ ﻪﺠﯿﺘﻧ نﺎﮔﺪﻨﺴﯾﻮﻧ .ﺖﻓﺎﯾ ﺶﻫﺎﮐ

ﮥ ﺶﻫﺎـﮐ

ﻞﻣﺎﻋ ﻪﺠﯿﺘﻧ رد و بﺎﻬﺘﻟا ﮏﻤﮐ

هﺪﻨﻨﮐ ﻪﯿﻟوا ﺖﻟﺎﺣ ﻪﺑ ﺖﺸﮔزﺎﺑ رد ﻊﯾﺮﺴﺗ و يدﻮﺒﻬﺑ ﻪﺑ ﺖﺳا

) 36 ( زﺎﺳ . زا هدﺎﻔﺘـﺳا ﺎـﺑ شزرو ﻪﮐ يﺮﮕﯾد رﺎﮐو

نآ

ًﻻﺎﻤﺘﺣا نﺎﯿﺑ نژ ﺎﻫ ي ﻞﻣﺎﺷ ،ﺖﺳا هداد ﺶﻫﺎﮐ ار ﺮﯿﺴﻣ ﻦﯾا لﺎﻌﻓ

زﺎﺳ ي شزرو .ﺖﺳاAMPK

ﻣ ﯽ ﺪﻧاﻮﺗ زﺎﻨﯿﮐ ﻦﯿﺌﺗوﺮﭘ لﺎﻌﻓ

هﺪﺷ ﻂـﺳﻮﺗ

و يژﺮﻧا ﺮﮕﺴﺣ ﮏﯾ ﻪﮐ ارAMP

ﻈﻨﺗ ﯿ ﻢ ﺪﻨﻨﮐ ة ﺖﺧﻮﺳ زﺎﺳو ﺪـﻨﮐ لﺎـﻌﻓ ،ﺖﺳا ﯽﻟﻮﻠﺳ )

37 ( ) نارﺎـﮑﻤﻫ و كرﺎـﭘ . 2011

ﻪـﮐ ﺪـﻧداد نﺎـﺸﻧ (

لﺎﻌﻓ زﺎﺳ ي نﺎﯿﺑ ﺶﻫﺎﮐ ﻖﯾﺮﻃ زاAMPK

نژ ﺎﻫ ي فﺪﻫ

3

STAT

ﺮﯿﺴﻣ

JAK/STAT

ار رﺎﻬﻣ ﻣ ﯽ ﺪﻨﮐ ) 38 ( . ﺞﯾﺎﺘﻧ ﻦﯾا ﺎﺑ ﻮﺴﻤﻫ ﻣ

ﯽ ناﻮﺗ

ﺖﻔﮔ ياﺮﺟا ﻣﺎﻧﺮﺑ ﮥ رد ﯽﺘﻣﺎﻘﺘﺳا نﺪﯾود ﯽﺷزرو تﺎﻨﯾﺮﻤﺗ ﻖﯿﻘﺤﺗ

،ﺮﺿﺎﺣ

ًﻻﺎﻤﺘﺣا ﻖﯾﺮﻃ زا لﺎﻌﻓ زﺎﺳ ي يﺎﻫﺮﯿﺴﻣ ﯾ

هﺪﺷدﺎ نﺎﯿﺑ نژ ﺎﻫ ي ﺮﯿـﺴﻣ

JAK/STAT

.ﺖﺳا هداد ﺶﻫﺎﮐ ار رﺎﮐوزﺎﺳ

ﻪﮐ يﺮﮕﯾد ﯽﻟﺎﻤﺘﺣا ﻪﺑ

ﺳو ﯿﻠ ﮥ ﻣﺎﻧﺮﺑ نآ ﮥ ﯽـﻣ ﯽﺘﻣﺎﻘﺘﺳا يود ﯽﺷزرو ﻦـﯾا نﺎـﯿﺑ ﺪـﻧاﻮﺗ

نژ ﺎـﻫ ار

ﺪﻫد ﺶﻫﺎﮐ

، ﺳا ﯽﺸﯾﺎﺴﮐا سﺮﺘﺳا ﺪﯿﻟﻮﺗ رد ﻪﭼﺮﮔا .ﺖ

ﺶﻫوﮋﭘ ﺮﺿﺎﺣ ﺺﺧﺎﺷ ﺎﻫ ﯽﺸﯾﺎﺴﮐا سﺮﺘﺳا ي هزاﺪﻧا

ﮔﯿ ﺮ هﺪﺸﻧ ي ،ﺪﻧا ﺖـﺳا ﺺﺨـﺸﻣ

شزرو ﻪﮐ ﻣ

ﯽ ﺪﻧاﻮﺗ ﺎﻘﻟا ار ﯽﺸﯾﺎﺴﮐا سﺮﺘﺳا ﻨﮐ

) نارﺎﮑﻤﻫ و نﺎﻓ .ﺪ 2018

ﯽﺸﯾﺎﺴﮐا سﺮﺘﺳا ﻪﮐ ﺪﻨﺘﻓﺎﯾرد ( ﻪﺑ

ﺳو ﯿﻠ ﮥ نﻮﯿـﺳﻼﯾرﻮﻔﺴﻓ ﺶﻫﺎـﮐ

3

وSTAT 1

ﺮﯿﺴﻣJAK STAT

رﺎﻬﻣ ارJAK/

ﻣ ﯽ ﺪﻨﮐ ) 39 ( ﺞﯾﺎﺘﻧ ﺎﺑ ﻪﮐ ﻖﯿﻘﺤﺗ

نارﺎـﮑﻤﻫ و ﻦﯿﻟﺎـﺳ ،ﺮـﮕﯾد فﺮﻃ زا .ﺖﺳا ﻖﻓاﻮﻣ ﺮﺿﺎﺣ

) 2010 نﺎﺸﻧ ( ﺪﯿﻟﻮﺗ شزرو ﻪﮐ ﺪﻧداد ﻪﻧﻮﮔ

ﺎﻫ ي ﺶﯾاﺰﻓا ار ﯽﺸﻨﮐاو نﮋﯿﺴﮐا ﻣ

ﯽ ﺪﻫد ) 40 ( ) نارﺎﮑﻤﻫ و ﮓﻧاژ . 2012

رد ( ﺶﻫوﮋﭘ نﺎـﺸﻧ دﻮﺧ

ﻞﻤﻋ ﻦﯾا ﺪﻧداد ﻣ

ﯽ ﺪﻧاﻮﺗ نﺎﯿﺑ ﻦﯾﺎﮐﻮﺘﯾﺎﺳ ﺮﮕﺑﻮﮐﺮﺳ ﺖﻣﻼﻋ

ﻫد ﯽ 3 )

3

ﺮﯿـﺴﻣ و هدﺮﮐ لﺎﻌﻓ ار (SOCS 3

STAT / 1

رﺎـﻬﻣ ارJAK

ـﻨﮐ ﺪ ) 41 ( .

) نارﺎﮑﻤﻫ و اﻮﻠﯿﺳ ﻦﯿﻨﭽﻤﻫ 2020

رد ( ﻖﯿﻘﺤﺗ شزرو ﻪﮐ ﺪﻧداد نﺎﺸﻧ يروﺮﻣ ﻣ

ﯽ ﺪﻧاﻮﺗ وﺮﮑﯿﻣ نﺎﯿﺑ ﺪﻨﮐ ﻢﯿﻈﻨﺗ ارRNA

) 42 ( ؛ يﺎـﻫRNA

ﻢﯿﻈﻨﺗ ار نژ نﺎﯿﺑ يرﺎﮕﻧﺰﻣر نوﺪﺑ ﮏﭼﻮﮐ ﻣ

ﯽ ﺪﻨﻨﮐ ﻮﯿﺗاﺪﯿـﺴﮐا ﺐﯿـﺳآ و ﯽﺑﺎﻬﺘﻟا ﻞﻣاﻮﻋ ﺎﺑ ﺎﻬﻧآ ﻞﻣﺎﻌﺗ رد ﺖﻟﺎﺧد ﻪﮐ ﺖﺳا هﺪﺷ هداد نﺎﺸﻧ و

ﻪﺑ ناﻮﻨﻋ ﺖﺑﺎﯾد ضراﻮﻋ ياﺮﺑ ﯽﻧﺎﻣرد يﺎﻫرﺎﮑﻫار زا ﯽﮑﯾ ﺖﺳا

) 4 ( رد . ﻖﯿﻘﺤﺗ ) نارﺎﮑﻤﻫ و روﺮﺳ 2021

( وﺮـﮑﯿﻣ ﻦﯾﺪـﻨﭼ ﻪـﮐ ﺪﺷ ﺺﺨﺸﻣ

ﺮﯿﺴﻣ ياﺰﺟا ﺎﻫRNA TAT

JAK/S

ار راﺮﻗ فﺪﻫ ﯽﻣ

ﺪﻫد ﺖﯿﻟﺎﻌﻓ و رﺎﻬﻣ ار نآ ﻣ

ﯽ ﺪﻨﮐ ) 43 ( ﻪﺠﯿﺘﻧ رد . ﻣ

ﯽ ناﻮﺗ ياﺮـﺟا ﻪﮐ ﺖﻓﺮﮔ ﻪﺠﯿﺘﻧ

يود تﺎﻨﯾﺮﻤﺗ يور ﯽﺘﻣﺎﻘﺘﺳا

نادﺮﮔ راﻮﻧ ﻦﯾا ﻖﯾﺮﻃ زا ﺖﺳا ﻦﮑﻤﻣ

رﺎﮐوزﺎﺳ نﺎﯿﺑ نژ ﺎﻫ ي ﺮﯿﺴﻣ

JAK/STAT

رد ﻦﯾاﺮﺑﺎـﻨﺑ و هدﺮـﮐ رﺎﻬﻣ ار

زا ﯽﺷﺎﻧ ءﻮﺳ رﺎﺛآ ﺎﺑ ﻪﻠﺑﺎﻘﻣ لﺎﻌﻓ

زﺎﺳ ي ﺑﯿ ﺶ ﺪﺣزا .ﺖﺳا هدﺮﮐ ﻪﻠﺑﺎﻘﻣ نآ ﻪﺑ

رﻮﻃ شزرو ﯽﻠﮐ ﻣ

ﯽ ﺪﻧاﻮﺗ ﻦـﯾا ﻖـﯾﺮﻃ زا ﺎﻫرﺎﮐوزﺎـﺳ

ﻦـﯾا ﺖـﯿﻟﺎﻌﻓ

د ﺶﻫﺎﮐ ار ﺮﯿﺴﻣ ﺪﻫ

رﺎﺛآ رد و ﺖﮐرﺎﺸﻣ يرﺎﻤﯿﺑ زا يﺮﯿﮕﺸﯿﭘ و ﯽﺘﻣﻼﺳ يور نآ ﺪﯿﻔﻣ ﯾﻮﺟ

.ﺪ

ﯾ ﻪﺘﻓﺎ ﺎﻫ ي ﻖﯿﻘﺤﺗ ﻦﯿﺳﻮﺗوزﻮﺘﭘﺮﺘﺳا ﻖﯾرﺰﺗ ﻪﮐ داد نﺎﺸﻧ ﺮﺿﺎﺣ ﻪﺑ

رﻮﻈﻨﻣ ﺮﯿﺴﻣ رد لﻼﺘﺧا نآ ﯽﭘ رد و ﺖﺑﺎﯾد يﺎﻘﻟا

JAK1/STAT3

ﻪﺑ ناﻮﻨﻋ ﺮﯿﯿﻐﺗ ﺖﺴﻧاﻮﺘﻧ ﺖﺑﺎﯾد ﯽﺒﻧﺎﺟ ضراﻮﻋ زا ﯽﮑﯾ ﻨﻌﻣ

ﺎ راد ي نﺎﯿﺑ رد لﺮﺘﻨﮐ هوﺮﮔ ﻪﺑ ﺖﺒﺴﻧ نژ

ﻫﺎ ي فﻼﺧ ﺮﺑ .ﺪﻨﮐ دﺎﺠﯾا ﺮﯿﺴﻣ ﻦﯾا

عﻮﻧ ﺖﺑﺎﯾد يﺎﻘﻟا رﺎﻈﺘﻧا 1

نﺎﯿﺑ ﺶﯾاﺰﻓا ﺐﺟﻮﻣ ﻦﯿﺳﻮﺗوزﻮﺘﭘﺮﺘﺳا ﻖﯾرﺰﺗ ﺎﺑ نژ

ﺎﻫ ي ﺎﯾ JAK1 STAT3

،ﺖﺳا بﺎﻬﺘﻟا ﺶﯾاﺰﻓا ﺖﻣﻼﻋ ﻪﮐ

زا ﯽﮑﯾ ﻦﻣﺰﻣ بﺎﻬﺘﻟا ﺶﯾاﺰﻓا ؛ﺪﺸﻧ ﻪﻧﺎﺸﻧ

ﺎﻫ ي ﻪﺑ ﺖﺑﺎﯾد يرﺎﻤﯿﺑ رد لﻮﻤﻌﻣ رﺎﻤﺷ

ﻣ ﯽ آﯾ ﺪ ﻦﻣﺰﻣ بﺎﻬﺘﻟا . ﻣ

ﯽ ﺪﻧاﻮﺗ ﺮﯿﺴﻣ

JAK1/STAT3

ار

ﮐ لﺎﻌﻓ ﺪﻨ ﮥﻌﺳﻮﺗ ﻪﺑ و ﺑﯿ

رﺎﻤ ي ﺎﻫ ي ﻒﻠﺘﺨﻣ ﺮﺠﻨﻣ نﺎﯿﺑ ﺮﯿﯿﻐﺗ مﺪﻋ .دﻮﺷ نژ

ﺎﻫ ي ﻪﺑ ﺮﯿﺴﻣ ﻦﯾا رد ﺖﺑﺎﯾد لﺎﺒﻧد

ﺶﻫوﮋﭘ ﺮﺿﺎﺣ ﻣ ﯽ ﺪﻧاﻮﺗ

ﯽﮑﯾ .ﺪﺷﺎﺑ ﻪﺘﻓﺮﮔ راﺮﻗ ﯽﻔﻠﺘﺨﻣ ﻞﻣاﻮﻋ شﻮﺨﺘﺳد ﻞﯾﻻد زا

ًﻻﺎﻤﺘﺣا هﺎﺗﻮﮐ رود لﻮﻃ ندﻮﺑ ة

.ﺖﺳا ﻪﻌﻟﺎﻄﻣ ) نارﺎﮑﻤﻫ و راﻮﺘﺳا

2020 نﺎﺸﻧ (

ا ﻪﮐ ﺪﻧداد ﻪﮐ ﺖﺑﺎﯾد زا ﯽﺷﺎﻧ ﯽﺒﺼﻋ تﻻﻼﺘﺧا يﺎﻘﻟ

ﻪﺑ ناﻮﻨﻋ ﻪﺘﺧﺎﻨﺷ ﯽﻧاﻮﯿﺣ لﺪﻣ رد ﯽﺘﺑﺎﯾد ﯽﺗﺎﭘورﻮﻧ ﻣ

ﯽ دﻮﺷ 60 ﺖﺑﺎﯾد يﺎﻘﻟا زا ﺲﭘ زور

ﻖﯾرﺰﺗ ﻂﺳﻮﺗ ) ﻦﯿﺳﻮﺗوزﻮﺘﭘﺮﺘﺳا

mg/kg

65 ( خر ﻣ ﯽ ﺪﻫد ) 44 ( ) نارﺎﮑﻤﻫ و ﯽﻔﺠﻧ ﻦﯿﻨﭽﻤﻫ . 2017

ار تﺪﻣ ﻦﯾا ( ﺖﺸﻫ

يﺎﻘﻟا زا ﺲﭘ ﻪﺘﻔﻫ

ﻖﯾرﺰﺗ ﻂﺳﻮﺗ ﺖﺑﺎﯾد ) ﻦﯿﺳﻮﺗوزﻮﺘﭘﺮﺘﺳا

mg/kg

65 ( ﺪﻧدﺮﮐ ﺮﮐذ )

45 ( .

ًﻻﺎﻤﺘﺣا ﺮﯿﺴﻣ رد رﺎﻈﺘﻧا درﻮﻣ ﺞﯾﺎﺘﻧ ﻪﺑ ناﻮﺘﺑ هرود تﺪﻣ لﻮﻃ ﺶﯾاﺰﻓا ﺎﺑ

ﺮﻈﻧدرﻮﻣ ﺰﻐﻣ ،ﺮﮕﯾد يﻮﺳ زا .ﺖﻓﺎﯾ ﺖﺳد عﺎﻓد ﻢﺘﺴﯿﺳ ﮏﯾ زا

ﺘﻧآ ﯽ ﺴﮐا ﯿ ﻧاﺪ ﯽ ﯽﺑﺎﻬﺘﻟاﺪﺿ و ﻪﺑﺮﺼﺤﻨﻣ

دﺮﻓ ﺮﺑاﺮﺑ رد نآ زا ﻪﮐ ﺖﺳا رادرﻮﺧﺮﺑ

ﺖﻈﻓﺎﺤﻣ ﻢﺟﺎﻬﻣ ﻞﻣاﻮﻋ ﻣ

ﯽ ﺪﻨﮐ ) 46

، 47 ( ﻪﮐ دراد دﻮﺟو لﺎﻤﺘﺣا ﻦﯾا . هﺪﻘﻋ

ﺎﻫ ي هﺪﻋﺎﻗ ا ي ضراﻮﻋ ﺮﺑاﺮﺑ رد ﯽﻋﺎﻓد ﻢﺘﺴﯿﺳ ﻦﯾا زا هدﺎﻔﺘﺳا ﺎﺑ

نﺎﺸﻧ يﺮﺘﺸﯿﺑ ﺖﻣوﺎﻘﻣ نآ زا ﻞﺻﺎﺣ ﺞﯾﺎﺘﻧ و بﺎﻬﺘﻟا ﻪﻠﻤﺟ زا ﺖﺑﺎﯾد ﻣ

ﯽ ﺪﻨﻫد . ﯽﻓﺮﻃ زا ﺮﯿﺴﻣ

JAK/STAT

ﺮﯿﺴﻣ ﻤﻫاﺮﭘ ﯿﺘ ﯽ و ﻪﻌﺳﻮﺗ رد