تاثیرN-استیل سیستئین بر بیان ژن های MMP9 و TIMP2 در بافت کبدی رت های مواجهه یافته با کادمیوم

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه زیست شناسی، دانشکده علوم پایه، واحد رشت، دانشگاه آزاد اسلامی، رشت، ایران

2 گروه فارماسیوتیکس، دانشکده داروسازی، دانشگاه علوم پزشکی گیلان، رشت، ایران

10.22034/AEJ.2021.280495.2495

چکیده

هدف از این مطالعه تجربی بررسی اثر کادمیوم (Cd) بر بیان ژن­های ماتریکس متالوپروتئیناز 9 (MMP9) و مهارکننده بافتی متالوپروتئیناز 2 (TIMP2) و بررسی نقش محافظتی N-استیل سیستئین (NAC) بر سمیت کادمیوم در بافت کبد رت­ ها بود. در این مطالعه، رت­ های نر ویستار به ­طور تصادفی به 5 گروه: شاهد (G1)، تک دوز کادمیوم (80 میلی­ گرم/کیلوگرم) (G2)، دوز پیوسته کادمیوم (5/2 میلی   گرم/کیلوگرم) (G3)، تک دوز کادمیوم (80 میلی­ گرم/کیلوگرم) و دوز پیوسته NAC (50 میلی­ گرم/کیلوگرم) (G4) و دوز پیوسته کادمیوم (5/2 میلی ­گرم/کیلوگرم) و دوز پیوسته NAC (50 میلی ­گرم/کیلوگرم) (G5) تقسیم شدند. رنگ ­آمیزی هماتوکسیلین و ائوزین (H & E) برای مطالعه تغییرات هیستوپاتولوژی استفاده شد. غلظت کادمیوم به­ روش اسپکتروسکوپی کوره گرافیتی در نمونه­ های کبدی اندازه ­گیری شد. بیان ژن­ های MMP9 و TIMP2 با استفاده از RT-PCR ارزیابی شد. مواجهه با کادمیوم، به ­ویژه در دوز پیوسته با آسیب شدید بافتی و افزایش سلول­ های التهابی در بافت کبدی همراه بود. میانگین غلظت بافتی کادمیوم 27% در گروه G2 (P<0/05) و 60%  در گروه G3 (P<0/01) افزایش معنی­ دار داشت. تیمار با NAC در گروه G4  (P<0/01) و G5 (P<0/01) به ­طور معنی ­داری غلظت بافتی کادمیوم را کاهش داد. کادمیوم هم ­چنین بیان ژن MMP9 (P<0/001) و TIMP2 (P<0/01) را در گروه ­های G2 و G3 افزایش داد. تیمار با NAC به­ طور معنی­ داری این اثرات را معکوس کرد. یافته ­ها پیشنهاد می ­کنند که NAC سلول ­های کبدی را با کاهش تجمع کبدی کادمیوم و کاهش بیان ژن ­های TIMP2 و MMP9 محافظت می­ کند.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The effects of N-acetyl cysteine on the expression of MMP9 and TIMP2 genes in the liver tissue of cadmium exposed rats

نویسندگان [English]

  • Mohammad Mahdi Jafarzadeh 1
  • Najmeh Ranji 1
  • Ehsan Aboutaleb 2 1
1 Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran
2 Department of Pharmaceutics, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
چکیده [English]

The aim of this experimental study was to investigate the effect of cadmium (Cd) on the expression of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 2 (TIMP2) genes and to investigate the protective role of N-acetylcysteine ​​(NAC) on cadmium toxicity in the liver tissue of rats. In this study, male Wistar rats were randomly divided into 5 groups: control (G1), single dose of cadmium (80 mg/kg) (G2), continuous dose of cadmium (2.5 mg/kg) (G3), Single dose of cadmium (80 mg/kg) and continuous dose of NAC (50 mg/kg) (G4) and continuous dose of cadmium (2.5 mg/kg) and continuous dose of NAC (50 mg/kg) (G5). Hematoxylin and eosin (H&E) staining was used to study histopathological changes. Cadmium concentration was measured by graphite furnace spectroscopy in the liver samples. The expression of MMP9 and TIMP2 genes was evaluated using RT-PCR. Cadmium exposure, especially at continuous dose, was associated with severe tissue damage and increased inflammatory cells in the liver. The mean tissue of cadmium concentration was significantly increased by 27% (P<0.05) in the G2 group and 60% (P<0.01) in G3 group. NAC treatment in G4 group (P<0.01) and G5 group (P<0.01) significantly reduced the tissue concentration of cadmium. Cadmium also increased the expression of MMP9 gene (P<0.001) and TIMP2 gene (P<0.01) in G2 and G3 groups. NAC treatment significantly reversed these effects. Our results suggested that NAC protects liver cells by decreasing the accumulation of cadmium and reducing the expression of TIMP2 and MMP9 genes.

کلیدواژه‌ها [English]

  • Cadmium
  • MMP9
  • N-acetylcysteine
  • Oxidative stress
  • TIMP2

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فصلنامه محیط زیست جانوری
دوره 14، شماره 1
شماره بهار
اردیبهشت 1401
صفحه 101-108

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