Effect of isosorbide on matrix metalloproteinases activity of leukemic THP-1 and fibrosarcoma Wehi-164 cells in vitro Fatemeh Hajighasemi

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107

Effect of isosorbide on matrix metalloproteinases activity of leukemic THP-1 and fibrosarcoma Wehi-164 cells in vitro

Fatemeh Hajighasemi¹, Fatemeh Rezaeian²

1 Associate Professor, Department of Immunology, School of Medicine, Shahed University, Tehran, Iran 2 MD, Department of Immunology, School of Medicine, Shahed University, Tehran, Iran

(Received August 4, 2013; Accepted February 23, 2014)

Abstract

Background and purpose: Matrix metalloproteinases (MMPs) are a group of enzymes degredating the extracellular matrix. MMPs have an important role in inflammation, tumor growth, metastasis and angiogenesis.

Among the MMPs, MMP1 and MMP2 have special implication in angiogenesis. Isosorbide, as a nitric oxide donor, has been widely used in treatment of many cardiovascular diseases. Besides the inhibitory effect of isosorbide on angiogenesis, tumor growth and metastasis has been revealed in vivo. Regarding the important role of MMPs in tumor growth, metastasis and angiogenesis and also the suppressive effect of isosorbide on angiogenesis, tumor growth and metastasis, In this study, the isosorbide effect on MMP-2 and MMP-9 activity of leukemic and fibrosarcoma cells has been evaluated.

Materials and methods: The leukemic THP-1 and fibrosarcoma Wehi-164 cells were cultured in complete RPMI medium. Then the cells in the presence of phorbol myristate acetate (PMA) (25 ng/ml), incubated with different concentrations of isosorbide (0.0004, 0.004, 0.04, and 0.4 mM) for 24 hours. Thereafter, the isosorbide effect on MMP-2 and MMP-9 activity of the cells was evaluated by gelatin zymography assay. Statistical comparisons between the groups were done by analysis of variance (ANOVA).

Results: The MMPs activity of PMA-stimulated leukemic THP-1 and fibrosarcoma Wehi-164 cells treated with different concentrations of isosorbide did not show any statistical significant difference with untreated control cells.

Conclusion: The results of this study demonstrated that isosorbide had no statistical significant effect on MMPs activity of leukemic THP-1 and fibrosarcoma Wehi-164 cells. These findings proposed that anti- angiogenic effect of isosorbide, which was declared by other investigations, may possibly be owing to non-MMP activity mediated mechanisms.

Keywords: Isosorbide, matrix metalloproteinase, Wehi-164, THP-1

J Mazand Univ Med Sci 2014; 23(Suppl 2): 108-115 (Persian).

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لﻮﺌﺴﻣ ﻒﻟﻮﻣ ﻲﺟﺎﺣ ﻪﻤﻃﺎﻓ :

ﻲﻤﺳﺎﻗ ناﺮﻬﺗ - ﻪﻟاﺪﺒﻋنارداﺮﺑﺪﻴﻬﺷنﺎﺑﺎﻴﺧ،زروﺎﺸﻛراﻮﻠﺑ : هداز

، هرﺎﻤﺷ 31 E-mail: [email protected] .

1 رﺎﻴﺸﻧاد .

، ﻨﻤﻳاهوﺮﮔ ﻲ ﺳﺎﻨﺷ ﻲ

، ﻜﺷﺰﭘهﺪﻜﺸﻧاد ﻲ

، ا،ناﺮﻬﺗ،ﺪﻫﺎﺷهﺎﮕﺸﻧاد ﻳ

ناﺮ

2 ﻲﻣﻮﻤﻋﻚﺷﺰﭘ .

، ﻨﻤﻳاهوﺮﮔ ﻲ ﺳﺎﻨﺷ ﻲ

، ﭘهﺪﻜﺸﻧاد ﻜﺷﺰ ﻲ

، ا،ناﺮﻬﺗ،ﺪﻫﺎﺷهﺎﮕﺸﻧاد ﻳ

ناﺮ

نارﺪـــﻧزﺎــﻣﻲــــﻜــﺷﺰــﭘمﻮـــﻠــﻋهﺎﮕـــﺸـﻧادﻪــــﻠــﺠﻣ هرود مﻮﺳوﺖﺴﻴﺑ هﮋﻳو ﻪﻣﺎﻧ 2 ﺪﻨﻔﺳا لﺎﺳ 1392 ) 115 - 108 (

هدر رد ﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﺲﻜﻳﺮﺗﺎﻣ ﺖﻴﻟﺎﻌﻓ ﺮﺑ ﺪﻳﺎﺑرﻮﺳوﺰﻳا ﺮﺛا يﺎﻫ

ﻲﻟﻮﻠﺳ

ﻲﻳﺎﻣﻮﻛرﺎﺳ وﺮﺒﻴﻓ 164

- ﻚﻴﻤﺳﻮﻟ و Wehi

1 - ﻲﻫﺎﮕﺸﻳﺎﻣزآ ﻂﻳاﺮﺷ رد THP

ﺟﺎﺣﻪﻤﻃﺎﻓ ﻲ

ﻤﺳﺎﻗ ﻲ 1

نﺎﻴﺋﺎﺿرﻪﻤﻃﺎﻓ 2

هﺪﻴﻜﭼ

فﺪــﻫوﻪﻘﺑﺎــﺳ ﺎــﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎــﻣ:

MMPs) ﺎــﻳ Matrix metalloproteinases ﻢﻳﺰــﻧآزاﻲــﻫوﺮﮔ(

هﺪــﻨﻨﻛﻪــﻳﺰﺠﺗيﺎــﻫ

ﺪﻨﺘﺴﻫﻲﻟﻮﻠﺳجرﺎﺧﺲﻜﻳﺮﺗﺎﻣ ﻪﻛ

ﺰﻧژﻮﻳﮋﻧآ،بﺎﻬﺘﻟاردﻲﻤﻬﻣﺶﻘﻧ گر)

ﻲﻳاز

،( ﺪـﻧرادنﺎﻃﺮﺳزﺎﺘﺳﺎﺘﻣوﺪﺷر .

ﻚـﻳناﻮـﻨﻋﻪـﺑ،ﺪﻳﺎﺑرﻮـﺳوﺰﻳا

ﺪﻳﺎﺴﻛاﻚﻳﺮﺘﻴﻧهﺪﻨﻫد donor

NO) ﺎﻳ Nitric oxide وراد(

ﻲـﻳ ﺞـﻳار رد يرﺎـﻤﻴﺑنﺎـﻣرد ﺖـﺳاﻲـﺒﻠﻗيﺎـﻫ

. ،هوﻼـﻋﻪـﺑ ﻲﮔﺪـﻨﻨﻛرﺎـﻬﻣﺮـﺛا

وﺰﻳا ﺪﻳﺎﺑرﻮﺳ ﺮﺑ وﺪﺷر رﻮﻣﻮﺗزﺎﺘﺳﺎﺘﻣ ردﺰﻧژﻮـﻳﮋﻧآو

in vivo ﺪـﺷهدادنﺎـﺸﻧ

ﺖـﺳاه . ﻢـﻬﻣﺶـﻘﻧﻪـﺑﻪـﺟﻮﺗﺎـﺑ MMPs

وزﺎﺘـﺳﺎﺘﻣ،ﺪـﺷررد

يرﺎﻬﻣﺮﺛاﻪﺑﺮﻈﻧورﻮﻣﻮﺗﺰﻧژﻮﻳﮋﻧآ ﺪﻳﺎﺑرﻮﺳوﺰﻳا

،رﻮﻣﻮﺗﺰﻧژﻮﻳﺰﻧآوزﺎﺘﺳﺎﺘﻣ،ﺪﺷرﺮﺑ ﺖـﻴﻟﺎﻌﻓﺮـﺑﺪﻳﺎﺑرﻮـﺳوﺰﻳاﺮـﺛاﻪـﻌﻟﺎﻄﻣﻦـﻳارد

2 MMP - و

9 MMP - هدررد ﻲﻟﻮﻠﺳيﺎﻫ ﻲﻧﺎﻃﺮﺳ

ﻚﻴﻤﺳﻮﻟ 1

THP - ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓو 164

Wehi - ﻂﻳاﺮﺷرد in vitro

ﺮﮔراﺮﻗﻲﺳرﺮﺑدرﻮﻣ ﻓ

ﺖ .

شوروداﻮـﻣ ﺎـﻫ

لﻮﻠـﺳ: ﻂﻴـﺤﻣردﺖـﺸﻛزاﺲـﭘﺎـﻫ RPMI

Roswell Park Memorial Institute) ﻞـﻣﺎﻛ(

رﻮـﻀﺣرد، PMA

Phorbol myristate acetate) (

ng/ml) 25 روﺎﺠﻣرد ( ت ﺖﻈﻠﻏ ﺘﺨﻣيﺎﻫ تاﺮﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳاﻒﻠ )

4 /

،0 04 /

،0 004 / و0 0004 / ﻲﻠﻴﻣ0 رﻻﻮﻣ (

تﺪﻣﻪﺑ ﺪﻧﺪﺷﻪﺑﻮﻜﻧاﺖﻋﺎﺳ24

ﺖﻴﻟﺎﻌﻓﺲﭙﺳ . 2

MMP- و 9 MMP- لﻮﻠـﺳﺖـﺸﻛﻂﻴـﺤﻣرد درﻮـﻣﻲﻓاﺮﮔﻮـﻤﻳازﻦﻴـﺗﻻژشورﻪـﺑﺎـﻫ

ﺖﻓﺮﮔراﺮﻗﺶﺠﻨﺳ .

ﻪــﺘﻓﺎﻳ ﺎــﻫ ﺖــﻴﻟﺎﻌﻓناﺰــﻴﻣ: 2

MMP- و 9 MMP- لﻮﻠــﺳرد ﻚﻴﻤــﺳﻮﻟيﺎــﻫ 1

THP- رﺎــﺳوﺮﺒﻴﻓو ﻲﻳﺎﻣﻮﻛ

154 Wehi- رﻮــﻀﺣرد

ﺖﻈﻠﻏ ﺪﻳﺎﺑرﻮﺳوﺰﻳاﻒﻠﺘﺨﻣيﺎﻫ ﻲﻨﻌﻣتوﺎﻔﺗ

هوﺮﮔﺎﺑيراد ﺪﻫﺎﺷ

داﺪﻧنﺎﺸﻧ .

جﺎﺘﻨﺘﺳا : ﻪـﻌﻟﺎﻄﻣﻦـﻳارد

، ﺮﻴﺛﺄـﺗﺪﻳﺎﺑرﻮـﺳوﺰﻳا ﻲـﻨﻌﻣ

يراد ﺖـﻴﻟﺎﻌﻓﺮـﺑ 2

MMP- و 9 MMP- لﻮﻠـﺳرد يﺎـﻫ ﻚﻴﻤـﺳﻮﻟ 1

THP-

و ،ﺖـﺳاهﺪﺷشراﺰﮔناﺮﮕﻳدﻂﺳﻮﺗﻪﻛﺪﻳﺎﺑرﻮﺳوﺰﻳاﺰﻧژﻮﻳﮋﻧآﺪﺿﺖﻴﻟﺎﻌﻓدورﻲﻣلﺎﻤﺘﺣا .داﺪﻧنﺎﺸﻧ_Wehi-164ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ ﻲـﺷﺎﻧ

زا ﻢﺴﻴﻧﺎﻜﻣ يﺎﻫ) ﺮﮕﻳد ( ﺪﺷﺎﺑﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣزاﻞﻘﺘﺴﻣ .

هژاو يﺪﻴﻠﻛيﺎﻫ

،زﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ،ﺪﻳﺎﺑرﻮﺳوﺰﻳا : 164

Wehi-

، 1 THP-

ﻪﻣﺪﻘﻣ

ﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ Matrix metalloproteinases)

ﺎﻳ MMPs ﺮﮔ(

ﺲﻜﻳﺮﺗﺎـﻣهﺪﻨﻨﻛﻪﻳﺰﺠﺗيﺎﻫزاﺪﻴﺘﭙﭘوﺪﻧازاﻲﻫو

وشﺮﺘــﺴﮔ،ﺪــﺷرردﻲــﻤﻬﻣﺶــﻘﻧﻪــﻛﺪﻨﺘــﺴﻫﻲﻟﻮﻠــﺳجرﺎــﺧ ﺪــﻧرادرﻮــﻣﻮﺗزﺎﺘــﺳﺎﺘﻣ

) 3 - 1

.(

زاﻲــﻜﻳ ﻞــﻣاﻮﻋ ــﻣ ﺆ وﺪــﺷرردﺮﺛ

رﻮﻣﻮﺗزﺎﺘﺳﺎﺘﻣ

، ﺰﻧژﻮﻳﮋﻧآهﺪﻳﺪﭘ گر)

ﻲـﻳاز ( ﺖـﺳا

)

،5 4

.(

ﺶـﻘﻧ

يرﺎﻤﻴﺑردﺰﻧژﻮﻳﮋﻧآردﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ ﻒـﻠﺘﺨﻣيﺎﻫ

ﺰـــﮔ ﺖـــﺳاهﺪـــﺷشرا

) 8 - 6

.(

زﺎـــﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎـــﻣ -

2 ) 2 MMP- زﺎـﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣو ( -

9 ) 9 MMP- ( ﻪـﺑﻪـﻛ

ﺐﻴﺗﺮﺗ و72

،ﺪﻧرادنزونﻮﺘﻟادﻮﻠﻴﻛ92 ياراد

ﻲـﺻﺎﺧﺖـﻴﻤﻫا

نﺎﻃﺮﺳزﺎﺘﺳﺎﺘﻣوﺪﺷر،ﺰﻧژﻮﻳﮋﻧآهﺪﻳﺪﭘرد ﺪﻨﺘﺴﻫ

)

،10

،9 3

.(

ﺮﮕﻳدفﺮﻃزا

، وشﺮﺘـﺴﮔ،ﺪـﺷرردﻲﻤﻬﻣﺶﻘﻧﺰﻧژﻮﻳﮋﻧآ

ﺳﺎﺘﻣ نﺎﻃﺮﺳردرﻮﻣﻮﺗزﺎﺘ يﺎﻫ

نﻮﺧ ﻲﻤﺳﻮﻟ) ( ﺎﻣﻮﻛرﺎـﺳوﺮـﺒﻴﻓو

اد در

)

،12 11

ﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣو(

ﺰـﻴﻧ ﺖـﻴﻤﻫا هﮋـﻳو يا

ﻪــﺑﻼﺘــﺒﻣنارﺎــﻤﻴﺑوﻚﻴﻤــﺳﻮﻟنارﺎــﻤﻴﺑردﺰﻧژﻮــﻳﮋﻧآهﺪــﻳﺪﭘرد ﺪﻧرادﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ

) 15 - 13

.(

(3)

اﺮﺛا ﻳ ﺎﺑرﻮﺳﺰ ﻳ ﺪ ﻟﺎﻌﻓﺮﺑ ﻴ ﺖ ﺮﺗﺎﻣ ﻳ ﺲﻜ ﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﻴ ﺎﻫزﺎﻨ رد لﻮﻠﺳ ﺎﻫ ي ﻧﺎﻃﺮﺳ ﻲ

نارﺪﻧزﺎﻣﻲﻜﺷﺰﭘمﻮﻠﻋهﺎﮕﺸﻧادﻪﻠﺠﻣ مﻮﺳوﺖﺴﻴﺑهرود

هﮋﻳو، ﻪﻣﺎﻧ

،2 ﺪﻨﻔﺳا 1392

109

ﻲﻳوراد،ﺪﻳﺎﺴﻛاﻚﻳﺮﺘﻴﻧهﺪﻨﻫدﻚﻳناﻮﻨﻋﻪﺑ،ﺪﻳﺎﺑرﻮﺳوﺰﻳا اﺮــﺑلواﺪــﺘﻣ يرﺎــﻤﻴﺑنﺎــﻣردي

ﺖــﺳاﻲــﺒﻠﻗيﺎــﻫ

)

،17 16

.(

رد

ـﺑتﺎﻌﻟﺎﻄﻣ ﻪ

ﻞـﻤﻋ آ ﻲﻧﺎـﻣردتاﺮـﺛا،ناﺮﮕـﺸﻫوﮋﭘﻂـﺳﻮﺗهﺪـﻣ

ياﺮـﺑهﺮـﻴﻏويرﻮـﻣﻮﺗﺪﺿ،ﻲﺑﺎﻬﺘﻟاﺪﺿﺶﻘﻧﻪﻠﻤﺟزايﺮﮕﻳد ﺖﺳاهﺪﺷﺮﻛذﺪﻳﺎﺑرﻮﺳوﺰﻳا

) 20 - 18

.(

Vallance ارﺪﻳﺎﺑرﻮـﺳوﺰﻳاﻲﺑﺎـﻬﺘﻟاﺪﺿتاﺮﺛانارﺎﻜﻤﻫو

ﻛاﻚﻳﺮﺘﻴﻧﻲﮔﺪﻨﻫدﻲﮔﮋﻳوﻞﻴﻟدﻪﺑ يرﺎـﻤﻴﺑردورادﻦـﻳاﺪﻳﺎﺴ

ﺪــﻧدﺮﻛشراﺰــﮔهدورﻲﺑﺎــﻬﺘﻟا

) 18

.(

ﻦﻴــﻨﭽﻤﻫ Martelletti

و

ردبﺎـﻬﺘﻟارﺎـﻬﻣنارﺎﻜﻤﻫ ﺖـﻓﺎﺑ

زاﻲـﻧﺮﮕﻴﻣنارﺎـﻤﻴﺑﺰـﻐﻣيﺎـﻫ

ﺖﻴﺳﻮﻜﻟتﺮﺟﺎﻬﻣزاﺖﻌﻧﺎﻤﻣﻖﻳﺮﻃ لﻮﻠﺳﻦﻴﺑزالﺎﻌﻓيﺎﻫ

يﺎـﻫ

ﺪﻧدادنﺎﺸﻧارﺪﻳﺎﺑرﻮﺳوﺰﻳاﻂﺳﻮﺗلﺎﻴﻠﺗوﺪﻧا

) 19

.(

ﻪـﺑﻲـﺳرﺮﺑرد

ﻂــﺳﻮﺗهﺪــﻣآﻞــﻤﻋ Pipili-Synetos

نارﺎــﻜﻤﻫو رﺎــﻬﻣﺮــﺛا

ردﺪﻳﺎﺑرﻮــﺳوﺰﻳاﻂــﺳﻮﺗﺰﻧژﻮــﻳﮋﻧآوزﺎﺘــﺳﺎﺘﻣ،ﺪــﺷرﻲﮔﺪــﻨﻨﻛ لﺪﻣ ﺪﺷهدادنﺎﺸﻧﻲﻧاﻮﻴﺣيﺎﻫ

) 20

.(

ﺪـﺿوﻚـﻴﻧژﻮﻳﮋﻧآﺪـﺿ،يرﻮـﻣﻮﺗﺪـﺿتاﺮـﺛاﻪـﺑﻪـﺟﻮﺗﺎﺑ ﻲﺑﺎﻬﺘﻟا يوراد ﺪﻳﺎﺑرﻮﺳوﺰﻳا و

ـﻓﺮﻃزا

،ﻲ ﻢـﻬﻣﺶـﻘﻧ ردﺰﻧژﻮـﻳﮋﻧآ

ﻃﺮﺳردرﻮﻣﻮﺗزﺎﺘﺳﺎﺘﻣوشﺮﺘﺴﮔ،ﺪﺷر نﺎ

يﺎﻫ نﻮﺧ ﻲﻤـﺳﻮﻟ) و (

ﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ

)

،12 11

و(

ﻪﻛﻦﻳاﻪﺑﺮﻈﻧ ﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ

ﺖﻴﻤﻫا هﮋﻳو يا نارﺎﻤﻴﺑوﻚﻴﻤﺳﻮﻟنارﺎﻤﻴﺑردﺰﻧژﻮﻳﮋﻧآهﺪﻳﺪﭘرد

ﺪــﻧرادﺎﻣﻮﻛرﺎــﺳوﺮﺒﻴﻓﻪــﺑﻼﺘــﺒﻣ

) 15 - 13

؛(

ﻪــﻌﻟﺎﻄﻣﻦــﻳارد

، ﺮــﺛا

يﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎـﻣﺖـﻴﻟﺎﻌﻓﺮﺑﺪﻳﺎﺑرﻮﺳوﺰﻳا و2

9 ـﻛ) ﻪ

ياراد نﺎﻃﺮـﺳزﺎﺘﺳﺎﺘﻣوﺪﺷر،ﺰﻧژﻮﻳﮋﻧآهﺪﻳﺪﭘردﻲﺻﺎﺧﺖﻴﻤﻫا

ﺪﻨﺘــﺴﻫ هدررد( ﻲﻳﺎﻣﻮﻛرﺎــﺳوﺮﺒﻴﻓﻲﻟﻮﻠــﺳيﺎــﻫ 164

Wehi - و

THP - ﻂﻳاﺮـﺷرد in vitro

ﺖـﻓﺮﮔﻲـﺳرﺮﺑدرﻮـﻣ .

ﻪـــﺘﻓﺎﻳ ﻖـــﻴﻗدﻲـــﺳرﺮﺑردﺶﻫوﮋـــﭘﻦـــﻳازاﻞـــﺻﺎﺣيﺎـــﻫ ﺮـــﺗ

ﻢــﺴﻴﻧﺎﻜﻣ يﺎــﻫ)

ﻦﻴــﻨﭽﻤﻫوﺪﻳﺎﺑرﻮــﺳوﺰﻳاﻚــﻴﻧژﻮﻳﮋﻧآﺪــﺿﺮــﺛا (

ﺣاﺮﻃ شورﻦﺘﻓﺎﻳياﺮﺑيﺪﻌﺑتﺎﻌﻟﺎﻄﻣﻲ زاهدﺎﻔﺘـﺳاﻲﻟﺎﻤﺘﺣايﺎﻫ

يرﺎﻤﻴﺑنﺎﻣردردﺪﻳﺎﺑرﻮﺳوﺰﻳا ردﻲـﻤﻬﻣﺶـﻘﻧﺰﻧژﻮﻳﮋﻧآﻪﻛﻲﻳﺎﻫ

نآﺰﻧژﻮﺗﺎـــﭘ درادﺎـــﻫ

نﺎﻃﺮـــﺳﻪـــﻠﻤﺟزا) وﻚﻴﻤـــﺳﻮﻟيﺎـــﻫ

ﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ هاروﺪﻴﻔﻣ،(

دﻮﺑﺪﻫاﻮﺧﺎﺸﮔ .

شور و داﻮﻣ ﺎﻫ

داﻮﻣ ﺖـﺸﻛﻂﻴﺤﻣ RPMI

RoswellParkMemorialInstitute)

،( ﻲﻨﭘ

،ﻦﻴـﺴﻳﺎﻣﻮﺘﭘﺮﺘﺳا،ﻦﻴﻠﻴـﺳ Dimethyl sulfoxide

DMSO)

،(

Phorbol myristate acetate PMA)

( ﻮـﻠﺑنﺎـﭙﻳﺮﺗو )

ﺖﺧﺎـﺳ

ﺎﻤﮕﻴﺳﺖﻛﺮﺷ

، USA ﺪـﺷﻪﻴﻬﺗ ( . ﻪﻟﺎـﺳﻮﮔﻦﻴـﻨﺟمﺮـﺳ FBS)

ﺎـﻳ

Fetal bovine serum

( ﺖﺧﺎـــﺳ) ﺖﻛﺮـــﺷ Gibco

، USA (

ﺪﻳدﺮﮔيراﺪﻳﺮﺧ اﺮﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳاﺺﻟﺎﺧيوراد .

ت ISDN)

ﺎــﻳ Isosorbide dinitrate (

ﺖﺧﺎــﺳ) يزﺎــﺳورادﺖﻛﺮــﺷ ﺎﻬــﺳ

،لﻼــﻫ ناﺮــﻳا ﺪــﺷﻪــﻳﺪﻫ ( ﺖــﻴﻠﭘ .

ﺖــﺸﻛيﺎــﻫ و96

،ﻪــﻧﺎﺧ24

ﻚﺳﻼﻓ ﻪﻟﻮﻟوﺖﺸﻛيﺎﻫ برديﺎﻫ

ﻞﻳﺮﺘﺳاراد )

ﺖﺧﺎـﺳ ﺖﻛﺮـﺷ

،NUNC Falcon

، USA ﺪﻳدﺮﮔيراﺪﻳﺮﺧ ( .

ﺖﻈﻠﻏﻪﻴﻬﺗ تاﺮﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳايورادﻒﻠﺘﺨﻣيﺎﻫ

ردوراداﺪﺘﺑا DMSO

Dimethyl sulfoxide) ﺪﺷﻞﺣ (

يﺎـﻣدردهدﺎﻔﺘﺳانﺎﻣزﺎﺗو

°C 20 - ﺪـﺷيراﺪـﻬﮕﻧ .

ردﺲﭙـﺳ

لﻮﻠﺳرﺎﻤﻴﺗمﺎﮕﻨﻫ ﺖﻈﻠﻏ،ﺎﻫ

يﺎـﻫ 4 / 0 - 0004 / 0 زارﻻﻮـﻣﻲـﻠﻴﻣ

ﺖﺸﻛﻂﻴﺤﻣردوراد RPMI

ﺪﻳدﺮﮔﻪﻴﻬﺗ1640 .

هدر ﻲﻟﻮﻠﺳيﺎﻫ

هدر ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓﻲﻟﻮﻠﺳيﺎﻫ 164

Wehi- ﻚﻴﻤـﺳﻮﻟو

1 THP- ﻮﻠﺳﻚﻧﺎﺑزا ﻲﻟ

ردوﺪﻧﺪـﺷﻪـﻴﻬﺗناﺮﻳارﻮﺘﺳﺎﭘﻮﺘﻴﺘﺴﻧا

ﻂﻳاﺮــﺷ In vitro يوﺎــﺣﺖــﺸﻛﻂﻴــﺤﻣرد،

RPMI1640 و

FCS Fetal calf serum) (

ﺪــﺻرد10 يﺎــﻣدرد

°C و37

CO2

) ﺪﺻرد5 ﺪﻧﺪﺷهدادﺮﻴﺜﻜﺗوﺖﺸﻛ،( .

هزاﺪﻧا لﻮﻠﺳﺪﺻرديﺮﻴﮔ هﺪﻧزيﺎﻫ

لﻮﻠﺳرﺎﻤﻴﺗزاﻞﺒﻗ لﻮﻠـﺳﺪـﺻردﺶﺠﻨﺳرﻮﻈﻨﻣﻪﺑ،ﺎﻫ

يﺎـﻫ

اهﺪـــــﻧز ﮓـــــﻧرشورز ﻮـــــﻠﺑنﺎـــــﭙﻳﺮﺗﺎـــــﺑيﺰـــــﻴﻣآ

TB

Trypan blue dye exclusion) (

) 21

ﺪﺷهدﺎﻔﺘﺳا(

.

لﻮﻠﺳرﺎﻤﻴﺗ ﺎﻫ

لﻮﻠﺳ ﺪﺷرﻂﻳاﺮﺷردﺎﻫ ﺐﺳﺎﻨﻣ

هوﺮـﮔﻪـﺑ ﻲﻜﻫﺎـﭼﻪـﺳيﺎـﻫ

ﺪــﺷﻢﻴــﺴﻘﺗ ﺪﻧ

و 10⁶ ﻚــﻳردلﻮﻠــﺳ ﺖــﻴﻠﭘردml

ﺖــﺸﻛيﺎــﻫ

ﺖﺸﻛﻂﻴﺤﻣردﻪﻧﺎﺧ24 RPMI1640

يوﺎﺣ FCS 10 ﺪـﺻرد

ﺪﻧﺪﺷهدادﺖﺸﻛ ﮔﻚﻳ .

ردﺪﻫﺎﺷناﻮﻨﻋﻪﺑهوﺮ ﺪـﺷﻪﺘﻓﺮﮔﺮﻈﻧ

ﺪﻧ

هوﺮـــﮔو ﺖـــﻈﻠﻏتروﺎـــﺠﻣردﺮـــﮕﻳديﺎـــﻫ زاﻒـــﻠﺘﺨﻣيﺎـــﻫ

(4)

ﺪﻳﺎﺑرﻮـــﺳوﺰﻳا )

4 /

،0 04 /

،0 004 / و0 0004 / ﻲـــﻠﻴﻣ0 رﻻﻮـــﻣ رد (

رﻮﻀﺣ PMA ng/ml) 25 ( تﺪـﻣﻪﺑ 24 ﺪﻧﺪـﺷﻪـﺑﻮﻜﻧاﺖﻋﺎـﺳ .

ﺖﻈﻠﻏ يﺎﻫ ﻲﻠﺒﻗﻪﻌﻟﺎﻄﻣسﺎﺳاﺮﺑورادهدﺎﻔﺘﺳادرﻮﻣ

) 22

بﺎـﺨﺘﻧا(

ارداﺮﻳز؛ﺪﻧﺪﺷ ﺖﻈﻠﻏﻦﻳ

ﺮـﺑﻲﻤـﺳﺮﺛاﻪﻧﻮﮔﭻﻴﻫﺪﻳﺎﺑرﻮﺳوﺰﻳا،ﺎﻫ

لﻮﻠﺳ دراﺪﻧﻪﻌﻟﺎﻄﻣدرﻮﻣيﺎﻫ .

نﻮﻴـﺳﺎﺑﻮﻜﻧانﺎـﻣزيﺎﻀﻘﻧازاﺲﭘ

،

لﻮﻠﺳﺖﺸﻛﻂﻴﺤﻣﺖﻧﺎﺗﺎﻧﺮﭘﻮﺳزايراﺪﻘﻣ ﻊﻤﺟﺎﻫ

ﺖﻬﺟويروآ

ﺶﻳﺎﻣزآمﺎﺠﻧا ﻫﺎ

ي ردطﻮﺑﺮﻣ

°C 20 ﺪﻳدﺮﮔيراﺪﻬﮕﻧ - .

هزاﺪـﻧا شورﻪــﺑﺎــﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎــﻣﺖــﻴﻟﺎﻌﻓيﺮــﻴﮔ

ژ ﻲﻓاﺮﮔﻮﻤﻳازﻦﻴﺗﻻ

يﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣﺖﻴﻟﺎﻌﻓ و2

ﺖﺸﻛﻂﻴﺤﻣرد9

شورﻖﺑﺎـﻄﻣﻲﻓاﺮﮔﻮـﻤﻳازﻦﻴـﺗﻻژشورﻪﺑلﻮﻠﺳ ﻪـﺘﻓﺎﻳﻞﻳﺪـﻌﺗ

Kleiner و

Stetler-Stevenson هزاﺪﻧا

ﮔﻴ ﺮ ي ﺪﺷ

) 23

.(

اﻪﺑ ﻳ ﻦ

ﺖﻧﺎﺗﺎﻧﺮﭘﻮﺳﻪﻛترﻮﺻ ردزرﻮﻓوﺮﺘﻜﻟاﺖﺤﺗﻲﻟﻮﻠﺳﺖﺸﻛيﺎﻫ

لژ ﺪﺻرد10 وﺎﺣﺪﻴﻣآﻞﻳﺮﻛاﻲﻠﭘ تﺎﻔﻟﻮـﺳﻞﻴـﺳدودﻢﻳﺪﺳي

Sodium dodecyl sulfate- polyacrylamide gel ) electrophoresis ﺎـــﻳ

PAGE SDS - ﺎـــﺑهﺪـــﺷهﺰﻳﺮﻤﻴﻠﭘﻮـــﻛ (

mgl/ml رﻮـﻀﺣردﻦﻴﺗﻻژ2

SDS 1 / 0 ﺪـﺻرد ﺮـﻴﻏﻂﻳاﺮـﺷرد

وﺎــﻴﺣا ژﺎــﺘﻟوﺖــﺤﺗ تﺪــﻣﻪــﺑ80

ﺪــﻨﺘﻓﺮﮔراﺮــﻗﺖﻋﺎــﺳ3 زاﺪــﻌﺑ .

لژ،زرﻮﻓوﺮﺘﻜﻟا نﻮﺘﻳﺮﺗردﺎﻫ

100 X - ) 5 / د2 ﺪﺻر ( جرﺎـﺧﺖـﻬﺟ

ندﻮــﻤﻧ SDS يوﺎــﺣﺮﻓﺎــﺑﻚــﻳردﺲﭙــﺳوﺪــﺷهدادﻮــﺸﺘﺴﺷ

Tris-HCl M)

1 /

،0 4 / pH7 و ( CaCl2

mM) 10 يﺎــــﻣدرد (

°C 37 ﺪﻧﺪـﺷﻪـﺑﻮﻜﻧاﺐﺷﻚﻳتﺪﻣﻪﺑ

،نآزاﺲـﭘ . لژ

ﺎـﺑﺎـﻫ

ﻮﻠﺑﻲﺳﺎﻣﻮﻛﮓﻧر 5

/ ﺪﺻرد0 ﮓﻧر آ ﮓـﻧرﺲﭙـﺳويﺰـﻴﻣ يﺮـﺑ

ﺪﻧﺪﺷ . ﻚـﻴﺘﻴﻟﻮﺌﺗوﺮﭘﺖـﻴﻟﺎﻌﻓ آ

وﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎـﻣﻢﻳﺰـﻧ ـﺑزﺎـﻨﻴﺌﺗ

ﻪ

ﻲـﺑآﻪـﻨﻴﻣزﻚـﻳردﻦﻴـﺗﻻژﺰـﻴﻟزاﻲـﺷﺎﻧﺪﻴﻔﺳيﺎﻫﺪﻧﺎﺑترﻮﺻ ﻲﻣهدادﺺﻴﺨﺸﺗ ﺪﺷ

. ﺪـﻧﺎﺑﻪـﺑﺖﺒﺴﻧهﺪﺷﺰﻴﻟيﺎﻫﺪﻧﺎﺑﻲﺒﺴﻧﻢﺠﺣ

ﻢﺘـﺴﻴﺳزاهدﺎﻔﺘـﺳاﺎـﺑلﺮﺘﻨﻛ Gel documentation UVI Pro

) Vilber Lourmat, Marne-la-Vallee Cedex1 ﻪــﺴﻧاﺮﻓ،

(

هزاﺪﻧا ﺑوﺪﺷيﺮﻴﮔ ﻪ

ﻻژﺖﻴﻟﺎﻌﻓترﻮﺻ ﺪﻳدﺮﮔنﺎﻴﺑﻲﺒﺴﻧﻚﻴﺘﻴﻟﻮﻨﻴﺗ

.

ﺞﻳﺎﺘﻧيرﺎﻣآﻞﻴﻠﺤﺗ يﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣﺖﻴﻟﺎﻌﻓ و2

ﺖﺸﻛﻂﻴﺤﻣرد9

لﻮﻠﺳ ﻲﻃﻲﻧﺎﻃﺮﺳيﺎﻫ آ3

هزاﺪﻧاﻪﻧﺎﮔاﺪﺟﺶﻳﺎﻣز ﺞﻳﺎﺘﻧويﺮﻴﮔ

مﺮــــــــﻧدراو يرﺎــــــــﻣآراﺰــــــــﻓا

ﻪﺨــــــــﺴﻧSPSS 5

/ 11

version 11.5, SPSS Inc., Chicago, IL) ﺪﺷ (

. ﻦﻴﮕﻧﺎـﻴﻣ

درﺎﻴﻌﻣفاﺮﺤﻧاو هدا

ردهﺪﻣآﺖﺳدﻪﺑيﺎﻫ ﺖﻈﻠﻏ

ﻒـﻠﺘﺨﻣيﺎﻫ

ﺪﻳدﺮﮔﻦﻴﻴﻌﺗ،ﺪﻳﺎﺑرﻮﺳوﺰﻳايوراد .

ﻦﻴـﺑيرﺎـﻣآﻪـﺴﻳﺎﻘﻣﺲﭙـﺳ

هوﺮــﮔ ﺎــﺑﺎــﻫ زاهدﺎﻔﺘــﺳا نﻮــﻣزآ

Analysis of variance

ANOVA) مﺎــﺠﻧا (

ﺪــﺷ و 050 /

<0 ﻲــﻨﻌﻣP ﻪــﺘﻓﺮﮔﺮــﻈﻧردراد

ﺪﺷ .

ﺖـﻈﻠﻏﺮﻴﺛﺄـﺗﻪـﺑطﻮـﺑﺮﻣيﺎـﻫرادﻮﻤﻧ ﺮـﺑورادﻒـﻠﺘﺨﻣيﺎـﻫ

ﻜﻳﺮﺗﺎﻣﺖﻴﻟﺎﻌﻓ يﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲ

و2 هدررد9 لﻮﻠﺳيﺎﻫ يﺎـﻫ

ﻪﻌﻟﺎﻄﻣدرﻮﻣﻲﻧﺎﻃﺮﺳ

، مﺮﻧرد راﺰﻓا Excel ﺪﻧﺪﺷﻢﺳر .

ﻪﺘﻓﺎﻳ ﺎﻫ

١ يدﺪﻳﺎﺑرﻮـــﺳوﺰﻳايورادﺮـــﺛا - ﺖـــﻴﻟﺎﻌﻓﺮـــﺑتاﺮـــﺘﻴﻧ

2 - هدرردMMP

ﻲﻳﺎﻣﻮﻛرﺎـﺳوﺮﺒﻴﻓﻲﻟﻮﻠـﺳيﺎﻫ 164

- وWehi

- ﺎﺑهﺪﺷﻚﻳﺮﺤﺗTHP

PMA

ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓﻲﻟﻮﻠﺳهدر-

164 -

Wehi

كﺮﺤﻣرﻮﻀﺣمﺪﻋرد لﻮﻠﺳPMA

يﺎﻫ ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ

164 Wehi-

ﺖـﻴﻟﺎﻌﻓﻪـﺑطﻮـﺑﺮﻣﺺﺨـﺸﻣوﻒﻴﻌـﺿﺪﻧﺎﺑﻚﻳ،

2 MMP- ﺪــﻧدادنﺎــﺸﻧ PMA .

ﻲــﻨﻌﻣرﻮــﻃﻪــﺑ يراد

ﺖــﻴﻟﺎﻌﻓ

2 MMP- لﻮﻠﺳردار يﺎﻫ

ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ 164

Wehi- ﺲـﭘ

زا لﻮﻠﺳﺎﺑﻪﺴﻳﺎﻘﻣردنﻮﻴﺳﺎﺑﻮﻜﻧاﺖﻋﺎﺳ24 ﺶﻳاﺰﻓالﺮﺘﻨﻛيﺎﻫ

داد ﻳا . ﺖﻈﻠﻏردﺪﻳﺎﺑرﻮﺳوﺰ ﻒﻠﺘﺨﻣيﺎﻫ

، ﭻﻴﻫ ـﺗﻪﻧﻮﮔ ﺄ ﺮـﺑيﺮﻴﺛ

ﺖﻴﻟﺎﻌﻓ 2 MMP- لﻮﻠﺳرد يﺎﻫ ﻲﻳﺎﻣﻮﻛرﺎـﺳوﺮﺒﻴﻓ 164

Wehi-

داﺪـﻧنﺎﺸﻧ .

ﺖـﻈﻠﻏﺮـﺛا ﺮـﺑﺪﻳﺎﺑرﻮـﺳوﺰﻳاﻒـﻠﺘﺨﻣيﺎـﻫ

ﺖـﻴﻟﺎﻌﻓ

2 MMP- ﻮﻠـــﺳرد ل يﺎـــﻫ ﻲﻳﺎﻣﻮﻛرﺎـــﺳوﺮﺒﻴﻓ 164

Wehi- رد

هرﺎﻤﺷرادﻮﻤﻧ ﺖﺳاهﺪﺷهدادﺶﻳﺎﻤﻧ1

.

ﻚﻴﻤﺳﻮﻟﻲﻟﻮﻠﺳهدر-

1 - THP

لﻮﻠﺳ ﻚﻴﻤﺳﻮﻟيﺎﻫ 1

THP- ﭻﻴـﻫ،ﻚـﻳﺮﺤﺗنوﺪـﺑ ﻪـﻧﻮﮔ

ﺖﻴﻟﺎﻌﻓﻪﺑطﻮﺑﺮﻣﺪﻧﺎﺑ 2

MMP- ﺪـﻧداﺪﻧنﺎـﺸﻧ PMA .

رﻮـﻃﻪـﺑ

ﻲــﻨﻌﻣ ﺖــﻴﻟﺎﻌﻓيﺎــﻘﻟاﺐــﺟﻮﻣيراد 2

MMP- لﻮﻠــﺳرد يﺎــﻫ

THP- زاﺲﭘ 24 ﺎـﺑﻪـﺴﻳﺎﻘﻣردنﻮﻴﺳﺎﺑﻮﻜﻧاﺖﻋﺎﺳ

لﻮﻠﺳ ﺪﻳدﺮﮔلﺮﺘﻨﻛيﺎﻫ ﺖﻈﻠﻏردﺪﻳﺎﺑرﻮﺳوﺰﻳا .

ﻒـﻠﺘﺨﻣيﺎﻫ

،

(5)

،2 ﺪﻨﻔﺳا 1392

111

(A)

(B)

رادﻮﻤﻧ هرﺎﻤﺷ 1 ورادﺮﺛا : ي اﻳ ﺎﺑرﻮﺳوﺰ ﻳ ﺪ ﻟﺎﻌﻓﺮﺑ ﻴ ﺖ ﺮﺗﺎﻣ ﻳ ﺲﻜ ﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﻴ زﺎﻨ - 2 ) 2 MMP- هدررد ( ﺎﻫ ي ﻟﻮﻠﺳ ﻲ ﻓﻴ وﺮﺒ ﺎﻣﻮﻛرﺎﺳ ﻲﻳ 164 Wehi- و

ﻤﺳﻮﻟ ﻴ ﻚ 1 - ﺮﺤﺗTHP ﻳ ﻚ ﺎﺑهﺪﺷ PMA لﻮﻠﺳ . ﺎﻫ ي ﻓﻴ وﺮﺒ ﺎﻣﻮﻛرﺎﺳ ﻲﻳ 164 - ﻤﺳﻮﻟوWehi ﻴ ﻚ 1 - THP داﺪﻌﺗﻪﺑ) 10⁶ ردلﻮﻠﺳ ﻳ ﻚ ml

ﺤﻣ ﻴ ﻂ ﺖﺸﻛ ﺗ ( ﺮﺤ ﻳ ﻚ هﺪﺷ ﺎﺑ PMA ) ng/ml 25 تﺪﻣﻪﺑ ( ﺖﻈﻠﻏتروﺎﺠﻣردﺖﻋﺎﺳ24 ﺪﻳﺎﺑرﻮﺳوﺰﻳازاﻒﻠﺘﺨﻣيﺎﻫ

) 4 / 0 - 0004 / ﻣﻴ0 ﻠ ﻲ رﻻﻮﻣ (

ﺪﻨﺘﻓﺮﮔراﺮﻗ ﻟﺎﻌﻓ .

ﻴ ﺖ 2 - ﺤﻣردMMP ﻴ ﻂ لﻮﻠﺳﺖﺸﻛ ﺗﻻژشورﻪﺑﺎﻫ

ﻴ ﻦ از ﻳ ﻓاﺮﮔﻮﻤ ﻲ هزاﺪﻧا ﮔ ﻴﺮ ي ﺪﺷ ) . A از ( ﻳ ماﺮﮔﻮﻤ ﻟﺎﻌﻓ ﻴ ﺖ 2 - ردMMP

لﻮﻠﺳ ﺎﻫ ي ﻓﻴ وﺮﺒ ﺎﻣﻮﻛرﺎﺳ ﻲﻳ 164 - Wehi نﻮﺘﺳ. لﻮﻠﺳفﺮﻌﻣ1 ﺎﻫ

ي 164 - ﺗﻴWehi رﺎﻤ ﺖﺳاهﺪﺸﻧ نﻮﺘﺳ .

ﺎﻫ ي ﻟا2 ﻲ ﺖﻈﻠﻏفﺮﻌﻣ5 ﺎﻫ

ي

0004 /

،0 004 /

،0 04 / و0 4 / ﻣﻴ0 ﻠ ﻲ ازارﻻﻮﻣ ﻳ ﺎﺑرﻮﺳوﺰ ﻳ ﺪ نﻮﺘﺳو ﺖﺳالﺮﺘﻨﻛفﺮﻌﻣ6 ) .

B ﻟﺎﻌﻓ ( ﻴ ﺖ 2 - لﻮﻠﺳردMMP ﺎﻫ ي ﻓﻴ وﺮﺒ ﺎﻣﻮﻛرﺎﺳ ﻲﻳ

164 - ﻤﺳﻮﻟوWehi ﻴ ﻚ 1 - ﺮﺤﺗTHP ﻳ ﻚ ﺎﺑهﺪﺷ ازﻦﻜﺳاﻂﺳﻮﺗPMA

ﻳ ﮔﻮﻤ ماﺮ ﺴﻧادوﺎﻫ ﻴ ﺮﺘﻣﻮﺘ ي ﺎﻫﺪﻧﺎﺑ ي 2 - هزاﺪﻧاMMP ﮔ ﻴﺮ ي ﺪﺷ .

هداد ﻦﻴﮕﻧﺎﻴﻣ،ﺎﻫ زاهﺪﻣآﺖﺳدﻪﺑرﺎﻴﻌﻣفاﺮﺤﻧا±

ﺪﻨﺘﺴﻫﻒﻠﺘﺨﻣﺶﻳﺎﻣزآ3 .

05 / 0

<

ﻲﻨﻌﻣP ﻲﻣﻪﺘﻓﺮﮔﺮﻈﻧردراد دﻮﺷ

.

* 100 / 0

>

P

ﭻﻴﻫ ﺗﻪﻧﻮﮔ ﺄ ﺖﻴﻟﺎﻌﻓﺮﺑيﺮﻴﺛ 2

MMP- لﻮﻠﺳرد ﻚﻴﻤـﺳﻮﻟيﺎﻫ

1 THP- داﺪﻧنﺎﺸﻧ . ﺖـﻈﻠﻏﺮـﺛا ﺨﻣيﺎـﻫ

ﺮـﺑﺪﻳﺎﺑرﻮـﺳوﺰﻳاﻒـﻠﺘ

ﺖﻴﻟﺎﻌﻓ 2 MMP- لﻮﻠﺳرد ﻚﻴﻤﺳﻮﻟيﺎﻫ 1

THP- رد رادﻮـﻤﻧ

هرﺎﻤﺷ ﺖﺳاهﺪﺷهدادﺶﻳﺎﻤﻧ1 .

٢ يدﺪﻳﺎﺑرﻮـــﺳوﺰﻳايورادﺮـــﺛا - ﺖـــﻴﻟﺎﻌﻓﺮـــﺑتاﺮـــﺘﻴﻧ

9 - هدرردMMP

ﻲﻳﺎﻣﻮﻛرﺎـــــــﺳوﺮﺒﻴﻓﻲﻟﻮﻠـــــــﺳيﺎـــــــﻫ

164 - ﻚﻴﻤﺳﻮﻟوWehi

1 - ﺎﺑهﺪﺷﻚﻳﺮﺤﺗTHP

PMA

ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓﻲﻟﻮﻠﺳهدر-

164 -

Wehi

ﺳ لﻮﻠ يﺎﻫ ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ 164

Wehi - ،كﺮـﺤﻣﺮـﺛانوﺪـﺑ

ﭻﻴﻫ ﺖﻴﻟﺎﻌﻓﻪﺑطﻮﺑﺮﻣﺪﻧﺎﺑﻪﻧﻮﮔ 9

MMP - ﺪﻧداﺪﻧنﺎﺸﻧ PMA .

ﻪﺑ ﻲﻨﻌﻣرﻮﻃ

ﺖـﻴﻟﺎﻌﻓيﺎـﻘﻟاﺐـﺟﻮﻣيراد 9

MMP - لﻮﻠـﺳرد يﺎـﻫ

Wehi - زاﺲـﭘ 24 ردنﻮﻴـﺳﺎﺑﻮﻜﻧاﺖﻋﺎـﺳ

لﻮﻠﺳﺎﺑﻪﺴﻳﺎﻘﻣ ﺪـﻳدﺮﮔلﺮـﺘﻨﻛيﺎﻫ

. ﺖـﻈﻠﻏردﺪﻳﺎﺑرﻮـﺳوﺰﻳا يﺎـﻫ

ﻒﻠﺘﺨﻣ

، ﭻﻴﻫ ـﺗﻪﻧﻮﮔ ﺄ ﺖـﻴﻟﺎﻌﻓﺮـﺑيﺮﻴﺛ 9

MMP - لﻮﻠـﺳرد يﺎـﻫ

Wehi - داﺪﻧنﺎﺸﻧ ﺖﻈﻠﻏﺮﺛا .

ﻒـﻠﺘﺨﻣيﺎـﻫ

ﺮﺑﺪﻳﺎﺑرﻮﺳوﺰﻳا ﺖﻴﻟﺎﻌﻓ

9 MMP - لﻮﻠﺳرد يﺎـﻫ ﻲﻳﺎﻣﻮﻛرﺎـﺳوﺮﺒﻴﻓ

164 Wehi - رد هرﺎﻤﺷرادﻮﻤﻧ ﺶﻳﺎﻤﻧ2

ﺖﺳاهﺪﺷهداد .

ﻚﻴﻤﺳﻮﻟﻲﻟﻮﻠﺳهدر-

1 - THP

لﻮﻠﺳ ﺎـﻫ ي ﻤـﺳﻮﻟ ﻴ ﻚ 1 THP- ،كﺮـﺤﻣنوﺪـﺑ ـﻳ

ﻚ ﺪـﻧﺎﺑ

ﻌﺿ ﻴ ﻒ ﺖـﻴﻟﺎﻌﻓﻪـﺑطﻮـﺑﺮﻣﺺﺨﺸﻣو 9

MMP- ﺪـﻧدادنﺎـﺸﻧ .

6 5 4 3 2 1

) 2 - MMP ( 72

) KD ( MW

164 Wehi-

1 THP-

(6)

وWehi-164ﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻓﻴﻲﻟﻮﻠﺳيﺎﻫهدر رد (MMP-9)9-زﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣﺖﻴﻟﺎﻌﻓ ﺮﺑﺪﻳﺎﺑرﻮﺳوﺰاﻳيوراد ﺮﺛا :2 هرﺎﻤﺷرادﻮﻤﻧ ﻤﺳﻮﻟ ﻴ ﻚ 1 - ﺮﺤﺗTHP ﻳ ﻚ ﺎﺑ هﺪﺷ PMA لﻮﻠﺳ . ﺎﻫ ي ﻓﻴ وﺮﺒ ﺎﻣﻮﻛرﺎﺳ ﻲﻳ 164 - ﻤﺳﻮﻟ وWehi ﻴ ﻚ 1 - THP داﺪﻌﺗ ﻪﺑ) ml / 10⁶ ﺮﺤﺗ ( ﻳ ﻚ ﺎﺑ هﺪﺷ

PMA ) ng/ml 25 تﺪﻣﻪﺑ ( ﺖﻈﻠﻏتروﺎﺠﻣردﺖﻋﺎﺳ24

ﺪﻳﺎﺑرﻮﺳوﺰﻳازاﻒﻠﺘﺨﻣيﺎﻫ )

0004 / 0 - 4 / ﻣﻴ0 ﻠ ﻲ رﻻﻮﻣ ﺪﻨﺘﻓﺮﮔراﺮﻗ ( ﻟﺎﻌﻓ .

ﻴ ﺖ

9 - ﺤﻣردMMP ﻴ ﻂ ﺗﻻژشورﻪﺑلﻮﻠﺳﺖﺸﻛ ﻴ

ﻦ از ﻳ ﻓاﺮﮔﻮﻤ ﻲ هزاﺪﻧا ﮔ ﻴﺮ ي ﺪﺷ هداد . ﻦﻴﮕﻧﺎﻴﻣ،ﺎﻫ ﺮﺤﻧا±

زاهﺪﻣآﺖﺳدﻪﺑرﺎﻴﻌﻣفا ﺶﻳﺎﻣزآ3

ﺪﻨﺘﺴﻫﻒﻠﺘﺨﻣ .

05 / 0

<

ﻲﻨﻌﻣP ﻲﻣﻪﺘﻓﺮﮔﺮﻈﻧردراد دﻮﺷ

.

* 100 / 0 P >

ﻲﻨﻌﻣرﻮﻃﻪﺑPMA يراد

ﺖـﻴﻟﺎﻌﻓ 9 MMP- لﻮﻠـﺳردار يﺎـﻫ

THP- زاﺲﭘ 24 ﺎـﺑﻪـﺴﻳﺎﻘﻣردنﻮﻴﺳﺎﺑﻮﻜﻧاﺖﻋﺎﺳ

لﻮﻠــﺳ دادﺶﻳاﺰــﻓالﺮــﺘﻨﻛيﺎــﻫ ﺖــﻈﻠﻏردﺪﻳﺎﺑرﻮــﺳوﺰﻳا .

يﺎــﻫ

ﻒﻠﺘﺨﻣ ﭻﻴﻫ ﺗﻪﻧﻮﮔ ﺄ ﺖـﻴﻟﺎﻌﻓﺮﺑيﺮﻴﺛ 9

MMP- لﻮﻠـﺳرد يﺎـﻫ

ﻚﻴﻤــﺳﻮﻟ 1

THP- داﺪــﻧنﺎــﺸﻧ ﺖــﻈﻠﻏﺮــﺛا .

ﻒــﻠﺘﺨﻣيﺎــﻫ

ﺮــﺑﺪﻳﺎﺑرﻮــﺳوﺰﻳا ﺖــﻴﻟﺎﻌﻓ

9 MMP- لﻮﻠــﺳرد ﻚﻴﻤــﺳﻮﻟيﺎــﻫ

1 THP- رد هرﺎﻤﺷرادﻮﻤﻧ ﺖﺳاهﺪﺷهدادﺶﻳﺎﻤﻧ2

.

ﺚﺤﺑ

ﺎـﺗ،ناﺮﮕـﺸﻫوﮋﭘﻂـﺳﻮﺗهﺪـﺷمﺎـﺠﻧاتﺎـﻌﻟﺎﻄﻣﺮـﺑيروﺮﻣﺎﺑ ـﺗدرﻮـﻣردﻲﺗاﺪﻨﺘـﺴﻣنﻮﻨﻛ ﺄ

ﺖـﻴﻟﺎﻌﻓﺮـﺑﺪﻳﺎﺑرﻮـﺳوﺰﻳايورادﺮﻴﺛ

هدرردﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ ﻚﻴﻤﺳﻮﻟﻲﻟﻮﻠﺳيﺎﻫ

1 THP -

ﺖــﺳاهﺪــﺸﻧﺖــﻓﺎﻳﻲﻳﺎﻣﻮﻛرﺎــﺳوﺮﺒﻴﻓو ﻖــﻴﻘﺤﺗزاﻞــﺻﺎﺣﺞﻳﺎــﺘﻧ .

يﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎـﻣﺖﻴﻟﺎﻌﻓﻦﻴﺑﻪﻛدادنﺎﺸﻧﺮﺿﺎﺣ و2

هدررد9 ﻚﻴﻤــﺳﻮﻟﻲﻟﻮﻠــﺳيﺎــﻫ 1

THP - ﻲﻳﺎﻣﻮﻛرﺎــﺳوﺮﺒﻴﻓو 164

Wehi - د ر ﺖــﻈﻠﻏ تاﺮــﺘﻴﻧيدﺪﻳﺎﺑرﻮــﺳوﺰﻳاﻒــﻠﺘﺨﻣيﺎــﻫ

) 0004 / 0 - 4 / ﻲﻠﻴﻣ0 رﻻﻮﻣ ( ﺖـﻈﻠﻏﺮـﻫﻦﻴـﺑﻦﻴﻨﭽﻤﻫوﺮﮕﻳﺪﻜﻳﺎﺑ

هوﺮﮔﺎﺑ

،ﺪﻫﺎﺷ ﻲﻨﻌﻣفﻼﺘﺧا دراﺪﻧدﻮﺟويراد

.

ﻪﻄـﺳاوزاﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣ ،ﺰﻧژﻮـﻳﮋﻧآﻢـﻬﻣيﺎـﻫ

ﺪﻨﺘـــﺴﻫرﻮـــﻣﻮﺗزﺎﺘـــﺳﺎﺘﻣوشﺮﺘـــﺴﮔ

) 9 - 6

.( Ledingham و

ﻮﺧﻪﻌﻟﺎﻄﻣردنارﺎﻜﻤﻫ ﻂﻳاﺮـﺷردرادرﺎـﺑنﺎﻧزﺮﺑد

in vivo و

ﺖﺳﻼﺑوﺮﺒﻴﻓﺮﺑﻦﻴﻨﭽﻤﻫ ردرادرﺎـﺑﺮـﻴﻏنﺎـﻧزﻢـﺣرندﺮـﮔيﺎﻫ

ﻂﻳاﺮﺷ in vitro ﭻﻴـﻫتاﺮـﺘﻴﻧﻮﻨﻣﺪﻳﺎﺑرﻮﺳوﺰﻳاﻪﻛﺪﻧدادنﺎﺸﻧ،

ﻨﻌﻣﺮﻴﺛﺄﺗﻪﻧﻮﮔ ﻲ

ﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣﺢﺷﺮﺗناﺰﻴﻣﺮﺑيراد

دراﺪﻧ

) 24

ﺗﻪﻛ(

ﻳﺄ ﺑﺞﻳﺎﺘﻧهﺪﻨﻨﻛﺪﻴ ﻪ

ﺖﺳد آ ردهﺪﻣ ﺤﺗ ﺮﺿﺎﺣﻖﻴﻘ

ﺖﺳا ﻦﻴﻨﭽﻤﻫ . Medina ﺶﻴـﭘﻪـﻛﺪﻧدﺮﻛشراﺰﮔنارﺎﻜﻤﻫو

ﭙــﺳآيﺎــﻫوراد ﻴ

ــﺗﺪﻳﺎﺑرﻮــﺳوﺰﻳايوﺎــﺣﻦﻳﺮ ﺄ

ﺢــﺷﺮﺗﺮــﺑيﺮﻴﺛ

2 MMP- ﺪﻧراﺪﻧ

) 25

ﺗﻪﻛ(

ﻳﺄ ﻲﻣﺮﻴﺧاﻪﻌﻟﺎﻄﻣﺞﻳﺎﺘﻧﺮﺑيﺪﻴ ﺪﺷﺎﺑ

.

تﺎــﻌﻟﺎﻄﻣ،ﺮـﺿﺎﺣﺶﻫوﮋــﭘزاﻞـﺻﺎﺣﺞﻳﺎــﺘﻧﻪـﺑﻪــﺟﻮﺗﺎـﺑ Ledingham نارﺎــــــﻜﻤﻫو

) 24

ﻪــــــﻌﻟﺎﻄﻣو( Medina

و

نارﺎﻜﻤﻫ

) 25

ﺗمﺪﻋصﻮﺼﺧرد(

ﺄﺛ ﻴﺮ اﻳ ﺎﺑرﻮﺳوﺰ ﻳ ﺪ د ي ﻧﻴ تاﺮﺘ

164 Wehi-

1 THP-

(7)

،2 ﺪﻨﻔﺳا 1392

113

ﻲـﻣﺮـﻈﻧﻪـﺑ،ﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎـﻣﺖﻴﻟﺎﻌﻓﺮﺑ ﻪـﻛﺪـﺳر

ﻪـﺑﻪﺘـﺴﺑاوﺮـﻴﻏﺪﻳﺎﺑرﻮـﺳوﺰﻳاﻂـﺳﻮﺗﺰﻧژﻮـﻳﮋﻧآرﺎـﻬﻣﻢﺴﻴﻧﺎﻜﻣ ﺎــــﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎــــﻣ ﻲــــﻣ

ﺑ ــــﺷﺎ لﺎــــﻤﺘﺣاوﺪ دراد

ﻢﺴﻴﻧﺎﻜﻣ ﻞﻴﺧدهﺪﻳﺪﭘﻦﻳارديﺮﮕﻳديﺎﻫ ﺪﻨﺷﺎﺑ

ﺗرد . تﺎﻘﻴﻘﺤ

ﻂــﺳﻮﺗهﺪــﻣآﻞــﻤﻋﻪــﺑ Naslund

و Norrby

، يرﺎــﻬﻣﺮــﺛا

زاﻲـﺷﺎﻧﺰﻧژﻮﻳﮋﻧآﺖﻴﻟﺎﻌﻓﺮﺑتاﺮﺘﻴﻧﻮﻧﻮﻣﺪﻳﺎﺑرﻮﺳوﺰﻳا bFGF

Basic fibroblast growth factor) (

ﻞـﺧادردهﺪـﺷﺢﻴﻘﻠﺗ

ﺖــﺳاهﺪــﺷشراﺰــﮔقﺎﻔــﺻ

) 26

ﻲــﻣنﺎــﺸﻧﻪــﻛ(

ﺪــﺿﺮــﺛاﺪــﻫد

رﺎـﻬﻣزاﻲـﺷﺎﻧيدوﺪـﺣﺎـﺗﺖـﺳاﻦﻜﻤﻣﺪﻳﺎﺑرﻮﺳوﺰﻳاﺰﻧژﻮﻳﮋﻧآ ﻪﺑﻪﺘﺴﺑاوﺰﻧژﻮﻳﮋﻧآ ﺗوﺪﺷﺎﺑbFGF

ﻳﺄ زاﻞـﺻﺎﺣﺞﻳﺎـﺘﻧهﺪﻨﻨﻛﺪﻴ

ﺖﺳاﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣ .

ﻦﻴــﻨﭽﻤﻫ Martelletti لﻮــﻜﻟﻮﻣنﺎــﻴﺑﺶﻫﺎــﻛ،نارﺎــﻜﻤﻫو

هﺪﻨﺒــﺴﭼ 1 ICAM - هﺪﻫﺎــﺸﻣارﺪﻳﺎﺑرﻮــﺳوﺰﻳافﺮــﺼﻣزاﺲــﭘ

ﺪﻧدﺮﻛ

) 19

.(

لﻮﻜﻟﻮﻣﻢﻬﻣﺶﻘﻧﻪﺑﻪﺟﻮﺗﺎﺑ هﺪـﻳﺪﭘردهﺪﻨﺒﺴﭼيﺎﻫ

ﻧﺎﻜﻣﻚﻳدرادنﺎﻜﻣا،ﺰﻧژﻮﻳﮋﻧآ ﺪـﺿتاﺮـﺛاﺮـﮕﻳدﻲﻟﺎـﻤﺘﺣاﻢـﺴﻴ

لﻮﻜﻟﻮﻣنﺎﻴﺑﺶﻫﺎﻛ،ﺪﻳﺎﺑرﻮﺳوﺰﻳاﻚﻴﻧژﻮﻳﮋﻧآ ﺪﺷﺎﺑهﺪﻨﺒﺴﭼيﺎﻫ

.

ﺟﺎـــﺣﻂـــﺳﻮﺗهﺪـــﻣآﻞـــﻤﻋﻪـــﺑﻪـــﻌﻟﺎﻄﻣرد ﻲ

ﻤـــﺳﺎﻗ ﻲ و

ﻣﻴ ﻔﺷﺮ ﻴﻌ ﻲ

) 27

ﭻﻴـﻫتاﺮﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳاﻪﻛﺪﺷهدادنﺎﺸﻧ(

ﺗﺄ ﻲﻨﻌﻣﺮﻴﺛ ﺪـﻴﻟﻮﺗناﺰـﻴﻣﺮـﺑيراد ﻞـﻣﺎﻋ

قوﺮـﻋلﺎﻴﻠﺗوﺪـﻧاﺪـﺷر

VEGF) ﺎﻳ Vascular endothelial cell growth factor (

لﻮﻠﺳرد ﺖﺳاﻪﺘﺷاﺪﻧﻚﻴﻤﺳﻮﻟهدريﺎﻫ .

ﺟﺎـﺣﻪـﻌﻟﺎﻄﻣﺞﻳﺎﺘﻧ ﻲ

ﻤﺳﺎﻗ ﻲ و ﻣﻴ ﻔﺷﺮ ﻴﻌ ﻲ

) 27

ﺗﺄ(

ﻪـﺘﻓﺎﻳهﺪﻨﻨﻛﺪﻴﻳ ﺮـﺿﺎﺣﻪـﻌﻟﺎﻄﻣيﺎـﻫ

ﺖﺳا

؛ اﺮﭼ ﻪﻛ ﺮﺗﺎﻣوVEGF

ﻳ ﺲﻜ ﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﻴ

،ﺎﻫزﺎﻨ ءﺰـﺟودﺮﻫ

ﻞﻣاﻮﻋ ﻣ ﺆ ﺮﻓردﺮﺛ اﻳ ﺪﻨ آ ﮋﻧ ﻳ ﺰﻧژﻮ ﺪﻨﺘـﺴﻫ ـﻨﭽﻤﻫو ﻴ ﻦ 2 MMP - رد

ﻈﻨﺗ ﻴ ﻢ ﻟﻮﺗ ﻴﺪ ﺗ،VEGF ﺄﺛﻴ راﺬﮔﺮ ﺖـﺳا

)

،29 28

.(

اﺮﺑﺎـﻨﺑ ﻳ

،ﻦ ﺮـﻈﻧﻪـﺑ

ﻣ ﻲ ﺗمﺪﻋﺪﺳر ﺄﺛﻴ

ﺮ اﻳ ﺎﺑرﻮﺳوﺰ ﻳﺪ ﺮﺑ ﻟﻮﺗ ـﻴ ﺪ VEGF ﻪـﻌﻟﺎﻄﻣردﻪـﻛ

ﺟﺎﺣ ﻲ ﻤﺳﺎﻗ ﻲ و ﻣﻴ ﻔﺷﺮ ﻴﻌ ﻲ

) 27

ﺪﺣﺎﺗ،ﺖﺳاهﺪﺷﺮﻛذ(

ي ﺷﺎﻧ ﻲ زا

ﺗمﺪﻋ ﺄﺛﻴ ﺮ اﻳ ﻦ ﻟﺎﻌﻓﺮﺑوراد ﻴ

ﺖ 2 MMP - ﺪﺷﺎﺑ .

ﺟﺎﺣﻂﺳﻮﺗهﺪﺷمﺎﺠﻧاﺮﮕﻳدﻪﻌﻟﺎﻄﻣرد ﻲ

ﻤﺳﺎﻗ ﻲ و ناﻮـﺿر

ﻲﻧﺪﻣ ﺗتاﺮﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳاﻪﻛﺖﺳاهﺪﺷشراﺰﮔ ﺄ

ﺮـﺑيﺮﻴﺛ

لﻮﻠــــــﺳيﺮــــــﻴﺜﻜﺗﺖــــــﻴﻟﺎﻌﻓ ﻲﻳﺎﻣﻮﻛرﺎــــــﺳوﺮﺒﻴﻓيﺎــــــﻫ

164 Wehi- ﺖــﺳاﻪﺘــﺷاﺪﻧ ﺎــﺘﻧ .

ﻳ ﺞ ﺟﺎــﺣﻪــﻌﻟﺎﻄﻣ ﻲ

ﻤــﺳﺎﻗ ﻲ و

ﻲﻧﺪﻣناﻮﺿر ﻲﻣ

ﺮـﻴﻏرﻮﻃﻪﺑﺪﻧاﻮﺗ ﻘﺘـﺴﻣ

ﻴ ﻢ ﺗﺄ ـﻴﻳ ﺪ ﺎـﺘﻧهﺪـﻨﻨﻛ ﻳ

ﺞ ﺪــﺷﺎﺑﺮــﺿﺎﺣﻪــﻌﻟﺎﻄﻣ

؛ ﻣﻪــﻛاﺮــﭼ ــﻴ

ناﺰ ﻟﺎﻌﻓ ــﻴ ﺖ ﺮﺗﺎــﻣ ﻳ ﺲﻜ

ﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﻴ ﺎﻫزﺎﻨ ﻣ ﻲ ﻪﺠﻴﺘﻧردونآﺪﻴﻟﻮﺗناﺰﻴﻣهﺪﻨﻫدنﺎﺸﻧﺪﻧاﻮﺗ

لﻮﻠـﺳﺮـﻴﺜﻜﺗناﺰﻴﻣﺮﮕﻧﺎﻳﺎﻤﻧ ﺪـﺷﺎﺑنآﺪـﻟﻮﻣيﺎـﻫ

) 22

.(

ﺮـﻈﻧﻪـﺑ

ﻲــﻣ ــﺗمﺪــﻋﺪــﺳر ﺄ

ﺖــﻴﻟﺎﻌﻓﺮــﺑتاﺮــﺘﻴﻧيدﺪﻳﺎﺑرﻮــﺳوﺰﻳاﺮﻴﺛ

2 MMP- و 9 MMP- زاﻲــﺷﺎﻧيﺪــﺣﺎــﺗ،ﺮــﺿﺎﺣﻪــﻌﻟﺎﻄﻣرد

ﺗمﺪﻋ ﺄ لﻮﻠﺳيﺮﻴﺜﻜﺗﺖﻴﻟﺎﻌﻓﺮﺑورادﺮﻴﺛ ﺪﺷﺎﺑﻪﻌﻟﺎﻄﻣدرﻮﻣيﺎﻫ

.

ﻂـــﺳﻮﺗهﺪـــﻣآﻞـــﻤﻋﻪـــﺑﻪـــﻌﻟﺎﻄﻣرد Pipili-Synetos

و

شﻮــﻣﺮــﺑنارﺎــﻜﻤﻫ ﺶﻫﺎــﻛ،ﻪــﻳرمﻮﻨﻴــﺳرﺎﻛﻪــﺑﻼﺘــﺒﻣيﺎــﻫ

لﻮﻠـﺳزﺎﺘـﺳﺎﺘﻣوﺰﻧژﻮـﻳﮋﻧآ،ﺪﺷررديﺮﻴﮕﻤﺸﭼ ﻲﻧﺎﻃﺮـﺳيﺎـﻫ

ﻂﻳاﺮـــﺷردﺪﻳﺎﺑرﻮـــﺳوﺰﻳاﻂـــﺳﻮﺗ in vivo

هﺪـــﺷشراﺰـــﮔ

ﺖـــﺳا

) 20

.(

ﻦﻴـــﻨﭽﻤﻫ Naslund

و Norrby ﺖـــﻴﻟﺎﻌﻓرﺎـــﻬﻣ،

ﻪﺑﻪﺘﺴﺑاوﺰﻧژﻮﻳﮋﻧآ bFGF

ﻂـﺳﻮﺗقﺎﻔـﺻﻞـﺧادردهﺪﺷﺢﻴﻘﻠﺗ

ﺪــﻧدادنﺎــﺸﻧارتاﺮــﺘﻴﻧيدﺪﻳﺎﺑرﻮــﺳوﺰﻳا

) 26

.(

ﻪــﺑتﺎــﻌﻟﺎﻄﻣرد

ﻂﺳﻮﺗهﺪﻣآﻞﻤﻋ Parinandi

ﻪﺑﺰﻧژﻮﻳﮋﻧآرﺎﻬﻣ،ﺰﻴﻧنارﺎﻜﻤﻫو

ﺪﻳﺎــﺴﻛاﻚــﻳﺮﺘﻴﻧهﺪــﻨﻫدﻚــﻳﻂــﺳﻮﺗزودﻪــﺑﻪﺘــﺴﺑاوترﻮــﺻ ﭙﺳآوﺮﺘﻴﻧ) ﻴ ﻦﻳﺮ ﺖﺳاهﺪﺷشراﺰﮔ،(

) 30

.(

ﺗﻞـﺑﺎﻗﻪـﺘﻜﻧ ﺄ

ﻦـﻳاﻞـﻣ

ﻌﻟﺎﻄﻣﻪﻛﺖﺳا ارﺪﻳﺎﺑرﻮﺳوﺰﻳاﻂﺳﻮﺗﺰﻧژﻮﻳﮋﻧآرﺎﻬﻣﻪﻛقﻮﻓتﺎ

هدﺮﻛشراﺰﮔ لﺪﻣرد،ﺪﻧا

ﻂﻳاﺮﺷوﻲﻧاﻮﻴﺣيﺎﻫ in vivo

مﺎﺠﻧا

هﺪــﺷ ﺪــﻧا ــﺑ . ﻪ هوﻼــﻋ

، رد ﻦــﻳا ﺲﻜﻳﺮﺗﺎــﻣﺖــﻴﻟﺎﻌﻓ،تﺎــﻌﻟﺎﻄﻣ

هزاﺪﻧاﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣ ﺖـﺳاهﺪـﺸﻧيﺮﻴﮔ

)

،26 20

؛(

ﺎـﻣا ﺶﻫوﮋـﭘ

ﻂﻳاﺮﺷردﺮﺿﺎﺣ in vitro

هدرﺮـﺑو ﻚﻴﻤـﺳﻮﻟﻲﻟﻮﻠـﺳيﺎـﻫ و

ﺖﺳاهﺪﺷمﺎﺠﻧاﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓ .

هﺪــﻴﭽﻴﭘهﺪــﻳﺪﭘﺰﻧژﻮــﻳﮋﻧآ وﻢﺟﺎــﻬﺗ،ﺪــﺷرردﻪــﻛﺖــﺳايا

درادﻲــﻤﻬﻣﺶــﻘﻧرﻮــﻣﻮﺗزﺎﺘــﺳﺎﺘﻣ

)

،5 4

.(

ﻞــﻣاﻮﻋ رديدﺪــﻌﺘﻣ

ﺮﻓ ا ﻦﻳﺎــﻛﻮﻤﻛزاترﺎــﺒﻋﻪــﻛﺪــﻧرادﺶــﻘﻧﺰﻧژﻮــﻳﮋﻧآﺪــﻨﻳ وﺎــﻫ

نآيﺎﻫرﻮﺘﭙــﺳر ﻦﻳﺎﻛﻮﺘﻳﺎــﺳ،ﺎــﻫ

،ﻲﺑﺎــﻬﺘﻟايﺎــﻫ ﻞــﻣاﻮﻋ

،ﺪــﺷر

ﻦﻳﺮﮕﺘﻨﻳا ﺲﻜﻳﺮﺗﺎﻣ،ﺎﻫ هﺮﻴﻏوﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣ

ﺪﻨﺘﺴﻫ

) 31

.(

هدﺮﺘﺴﮔﻪﻜﺒﺷﻪﻛﺐﻠﻄﻣﻦﻳايﺮﻴﮔﺮﻈﻧردﺎﺑ وﻞـﻣاﻮﻋزايا

ﺪـﻧرادﺶـﻘﻧﺰﻧژﻮـﻳﮋﻧآﻢﻴﻈﻨﺗردﻒﻠﺘﺨﻣيﺎﻫرﻮﺗﺎﻳﺪﻣ

) 31

ﺎـﺑو(

نﺎﻃﺮـﺳزﺎﺘـﺳﺎﺘﻣوﻢﺟﺎﻬﺗردﺰﻧژﻮﻳﮋﻧآﻢﻬﻣﺶﻘﻧﻪﺑﻪﺟﻮﺗ

)

،5 4

و(

ﺎﻣﻮﻛرﺎـﺳوﺮﺒﻴﻓوﻲﻤﺳﻮﻟردﺰﻧژﻮﻳﮋﻧآﻢﻬﻣﺶﻘﻧﻦﻴﻨﭽﻤﻫ

)

،12 11

،(

ﻲﺳرﺮﺑ ﺗﺄ ـﻣﻞـﻣاﻮﻋﺮﻳﺎـﺳﺮﺑﺪﻳﺎﺑرﻮﺳوﺰﻳاﺮﻴﺛ ﺆ

زاﺰﻧژﻮـﻳﮋﻧآﺮـﺑﺮﺛ

ﻪﻠﻤﺟ ﻞﻣاﻮﻋ لﻮـﻜﻟﻮﻣ،ﺪﺷر هدرردهﺮـﻴﻏوهﺪﻨﺒـﺴﭼيﺎـﻫ

يﺎـﻫ

(8)

رد،طﻮــﺑﺮﻣنارﺎــﻤﻴﺑوﻲﻳﺎﻣﻮﻛرﺎــﺳوﺮﺒﻴﻓوﻚﻴﻤــﺳﻮﻟﻲﻟﻮﻠــﺳ ﻂﻳاﺮﺷ in vitro و

in vivo ﻲﻣﺮﻈﻧﻪﺑيروﺮﺿ ﺪﺳر

.

ﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳاﻪﻛدادنﺎﺸﻧﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣﺞﻳﺎﺘﻧ تاﺮـﺘﻴ

ﺖﻈﻠﻏرد ﺑنﺎﻣزوﺎﻫ

ﻪ ﻪـﻧﻮﮔﭻﻴـﻫ،ﻪـﻌﻟﺎﻄﻣﻦـﻳاردﻪـﺘﻓررﺎﻛ

ــﺗ ﺄ ﺖــﻴﻟﺎﻌﻓﺮــﺑيﺮﻴﺛ 2

MMP - و 9 MMP - لﻮﻠــﺳرد يﺎــﻫ

دراﺪـﻧﻪﻌﻟﺎﻄﻣدرﻮﻣﻲﻳﺎﻣﻮﻛرﺎﺳوﺮﺒﻴﻓوﻚﻴﻤﺳﻮﻟ .

ﻪـﺑﻦﻳاﺮﺑﺎـﻨﺑ

ﻲﻣﺮﻈﻧ ﻪـﻛتاﺮـﺘﻴﻧيدﺪﻳﺎﺑرﻮﺳوﺰﻳايرﻮﻣﻮﺗﺪﺿتاﺮﺛاﺪﺳر

ﺶﻫوﮋــﭘﺮﻳﺎــﺳرد ﺖــﺳاهﺪــﺷشراﺰــﮔﺎــﻫ

)

،26 20

ﻲــﺷﺎﻧ،(

زا

ﺖـﻴﻟﺎﻌﻓﺮﻳﺎﺳﺮﺑوراديرﺎﻬﻣتاﺮﺛا لﻮﻠـﺳيﺎـﻫ

ﻲﻧﺎﻃﺮـﺳيﺎـﻫ

ﺎﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣﺖﻴﻟﺎﻌﻓزاﺮﻴﻏ) ﻦﻳاﺎﻳوﺪﺷﺎﺑ (

ﻪﺑﻪﻛ

لﻮﻠـﺳزاﻲـﻀﻌﺑﺖـﻴﻟﺎﻌﻓﺎـﻳداﺪـﻌﺗﺶﻳاﺰـﻓاﺖﻠﻋ ﻲـﻨﻤﻳايﺎـﻫ

ﺪﺷﺎﺑ

) 32

.(

ﻦﻴﻨﭽﻤﻫ ﻦﻳا

ﺖـﺳاﻦﻜﻤﻣﻪﻛ

ﻞـﻣاﻮﻋ رﺎـﻬﻣ هﺪـﻨﻨﻛ

ﺗﺄ ﻂﻳاﺮــﺷردراﺬــﮔﺮﻴﺛ in vivo

ﻲــﺳرﺮﺑﻞــﺑﺎﻗ، تﺎــﻌﻟﺎﻄﻣرد

in vitro ﺪﻨﺷﺎﺒﻧ

ﺮﻈﻧﻪﺑ . ﻲﻣ ﺮـﺑﺪﻳﺎﺑرﻮﺳوﺰﻳاﺮﺛاﻪﻌﻟﺎﻄﻣﺎﺑﺪﺳر

ﻞـﻣاﻮﻋﺮـﮕﻳدوﺎـﻫزﺎﻨﻴﺌﺗوﺮﭘﻮﻟﺎﺘﻣﺲﻜﻳﺮﺗﺎﻣعاﻮﻧاﺮﻳﺎﺳﺖﻴﻟﺎﻌﻓ ﻣ ﺆ لﻮﻠﺳردﺰﻧژﻮﻳﮋﻧآﺖﻴﻟﺎﻌﻓﺮﺑﺮﺛ يﺎـﻫ

ﻲـﻌﻴﺒﻃ رديرﻮـﻣﻮﺗو

وﻲﻫﺎﮕﺸﻳﺎﻣزآﻂﻳاﺮﺷ in vivo

ﻖﻴﻗدتﺎﻋﻼﻃا، درﻮﻣرديﺮﺗ

ﻢﺴﻴﻧﺎﻜﻣ ﮋﻧآرﺎﻬﻣيﺎﻫ ﺑﺪﻳﺎﺑرﻮﺳوﺰﻳاﻂﺳﻮﺗﺰﻧژﻮﻳ

ﻪ ﺪﻳآﺖﺳد .

ﻲـﻣتﺎﻌﻟﺎﻄﻣﻦﻳاﺞﻳﺎﺘﻧ شورﻲـﺣاﺮﻃردﺪـﻧاﻮﺗ

ﻲﻧﺎـﻣرديﺎـﻫ

يرﺎـﻤﻴﺑياﺮﺑﺪﻳﺎﺑرﻮﺳوﺰﻳازاهدﺎﻔﺘﺳاﺮﺑﻲﻨﺘﺒﻣ ردﻂﺒﺗﺮـﻣيﺎـﻫ

يرﺎـــﻤﻴﺑنﺎـــﻣردردورادﻦـــﻳادﺮﺑرﺎـــﻛرﺎـــﻨﻛ ﻲـــﺒﻠﻗيﺎـــﻫ

ﺪﺷﺎﺑﺪﻨﻣدﻮﺳ .

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