SIRT1在非酒精性脂肪肝病大鼠肝脏中的表达及姜黄素衍生物L6H4的干预作用

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Abstract Objective: To explore the expression changes of SIRT1 in rat liver with high-fat induced nonalcoholic fatty liver disease (NAFLD), and the effects of Curcumin derivatives L6H4 on it. Methods: Twenty-four male SD rats were randomly divided into normal control group (control group), model group (NAFLD group) and L6H4 treatment group (L6H4 group). Rats in the control group were fed with normal-diet while rats in NAFLD group and L6H4 group were fed with high-fat diet. At the same time, rats in L6H4 group were treated with Curcumin derivatives L6H4 from the 9th week till the 20th week of the experiment. At the end of the 20th week, all rats were sacrificed. The serum triglyceride, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were detected by biochemical method respectively. The pathological changes of liver tissues were observed by HE staining and Masson’s trichrome staining. The total SOD activity was detected by hydroxylamine method while the content of MDA was analyzed by thiobarbituric acid method.The expressions of SIRT1, DRP1 and MFN2 mRNA and protein in liver tissues were detected by real-time PCR and Western blot respectively. Results: Obvious steatosis and fibrosis were observed in NAFLD group under microscope. The pathological changes were significantly reduced in L6H4 group compared with NAFLD group. Compared with control group, the serum triglyceride, total cholesterol, low-density lipoprotein cholesterol levels, the content of MDA and the expression of DRP1 mRNA and protein were increased significantly, while the serum high-density lipoprotein cholesterol level, the total SOD activity and the expressions of SIRT1 and MFN2 mRNA and protein were decreased significantly (P<0.05) in NAFLD group. Compared with NAFLD group, the serum triglyceride, total cholesterol, low-density lipoprotein cholesterol levels, the content of MDA and the expression of DRP1 mRNA and protein were decreased significantly, while the serum high-density lipoprotein cholesterol level, the total SOD activity and the expressions of SIRT1 and MFN2 mRNA and protein were increased significantly (P<0.05) in L6H4 group. Conclusion: Curcumin derivatives L6H4 has a protective effect on NAFLD, and its mechanism may be through increasing the expression of SIRT1, thereby reducing the resistance of hepatocyte to insulin and lipid peroxidation, attenuating oxidative stress damage and inhibiting mitochondrial fission.

Key words： nonalcoholic fatty liver disease silent information regulator 1 dynamin-related protein 1 mitofusin 2

Received: 26 September 2017

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	DING Tingting
	WU Hangfei
	LIU Cheng
	TANG Wen
	WANG Shengkai
	ZHENG Jingyu
	ZHU Zaisheng
	PENG Tianqing.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I4/235

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