Chenari Sara, Safari Fatemeh, Moradi Ali
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Iran J Basic Med Sci. 2017 Dec;20(12):1306-1311. doi: 10.22038/IJBMS.2017.9609.
Bill duct ligation (BDL) is a representative model of biliary cholestasis in animals. Curcumin has a protective effect on the liver; however, its underlying mechanisms are not completely known. This study explored the hepatoprotective activity of curcumin on hepatic damage via measuring the expression of sirtuin3 (SIRT3), AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase 1A (CPT-1A), isocitrate dehydrogenase2 (IDH2) and manganese superoxide dismutase (MnSOD) as well as the level of serum lipid profile in the BDL fibrotic rat model.
The study consisted of four groups (n=8 for each of Wistar rats): sham group, sham+curcumin (sham+Cur) group (received curcumin 100 mg/kg/day), BDL+Cur group, and BDL group. Transcription levels of SIRT3, AMPK, CPT-1A, IDH2, MnSOD and protein expression level of SIRT3 were measured by real-time PCR and Western blotting, respectively.
It was identified that SIRT3, AMPK, CPT-1A, IDH2 and MnSOD expression significantly decreased in BDL rats compared to sham rats; however, in the curcumin treatment of BDL rats, the expression of these factors increased significantly compared to BDL (<0.05). It was, moreover, observed that treatment of BDL rats with curcumin reduced liver injury as verified by a reduction in the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) and increase in high-density lipoprotein (HDL) ( <0.05).
Curcumin reduced liver damage and oxidative stress in the liver tissue of BDL rats through up-regulation of SIRT3, AMPK, CPT-1A, IDH2 and MnSOD as well as changing the level of serum lipid profile.
胆管结扎(BDL)是动物胆汁淤积的代表性模型。姜黄素对肝脏具有保护作用;然而,其潜在机制尚不完全清楚。本研究通过测量沉默调节蛋白3(SIRT3)、AMP活化蛋白激酶(AMPK)、肉碱棕榈酰转移酶1A(CPT-1A)、异柠檬酸脱氢酶2(IDH2)和锰超氧化物歧化酶(MnSOD)的表达以及BDL纤维化大鼠模型中的血清脂质水平,探讨姜黄素对肝损伤的肝脏保护活性。
本研究包括四组(每组8只Wistar大鼠):假手术组、假手术+姜黄素(假手术+Cur)组(接受姜黄素100mg/kg/天)、BDL+Cur组和BDL组。分别通过实时PCR和蛋白质印迹法测量SIRT3、AMPK、CPT-1A、IDH2、MnSOD的转录水平和SIRT3的蛋白质表达水平。
与假手术大鼠相比,BDL大鼠中SIRT3、AMPK、CPT-1A、IDH2和MnSOD的表达显著降低;然而,在姜黄素治疗的BDL大鼠中,与BDL组相比,这些因子的表达显著增加(<0.05)。此外,观察到用姜黄素治疗BDL大鼠可减轻肝损伤,总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)水平降低,高密度脂蛋白(HDL)水平升高(<0.05),证实了这一点。
姜黄素通过上调SIRT3、AMPK、CPT-1A、IDH2和MnSOD以及改变血清脂质水平,减轻了BDL大鼠肝组织的肝损伤和氧化应激。