Effect of Vitamin E on the Expression of SIRT1 and PGC-1�� in Mice with Nonalcoholic Fatty Liver Disease
LI Jian-shuang1,2,CHEN Zhi-yun2,HONG Wei2*
1.Jinhua Municipal Central Hospital, Jinhua Hospital, Zhejiang University, Jinhua 321001,China; 2. The 1st Clinical Medical College of Zhejiang Traditional Chinese Medicine University, Hangzhou 310006, China
Abstract��OBJECTIVE To investigate the effect of vitamin E (Vit E) on the expression of SIRT1 and PGC-1�� in mice with nonalcoholic fatty liver disease(NAFLD), and to explore its role in the resistance against the oxidative stress.METHODS As animal models of NAFLD, Male C57BL/6 mice were fed with high-fat diets for 24 weeks,the model mice was administered Vit E (50 mg��kg-1��d-1) intragastrically for 18 weeks from 7th week of modeling .The pathological changes in liver were determined by HE and Masson staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) analyzed using automatic biochemical instrumentation. The levels of liver superoxide-dismutase (SOD) and MnSOD were tested by xanthine oxidase assay. Total content of malondialdehyde (MDA) in liver homogenate was tested by thiobarbituric acid (TBA) method. The mRNA and protein levels of silent mating type information regulation 2 homolog 1(SIRT1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1��) were tested by Real-time PCR and immunohistochemistry assay respectively.RESULTS Long-term high-fat diet induced NAFLD with the progression from liver steatosis, inflammatory response to fibrosis. The levels of serum ALT and AST in the rats of the NAFLD group were significantly higher than those of the normal group(P<0.05). The transcript and protein levels of liver SIRT1 and PGC-1�� were significantly decreased compared with the normal group. The total contents of liver SOD and MnSOD were much lower than those of the normal group, while the MDA level increased significantly(P<0.05).The administration of Vit E to some extent reduced inflammation and fibrosis.After Vit E treatment, the levels of serum ALT and AST were significantly lower than those of the model group(P<0.01, P<0.05). The mRNA and protein levels of liver SIRT1 and PGC-1�� became higher than those of the model group(P<0.05).Then liver SOD and MnSOD levels were significantly increased compared with the model group(P<0.05) while MDA content was reduced(P<0.05).CONCLUSION Vitamin E corrects the imbalances of the oxidative and antioxidative system in mice models of high-fat diet-induced NAFLD by regulating the expression levels of the key factors of the SIRT1/PGC-1�� signaling pathway, which reduces inflammation damage in liver and prevents the progression of NAFLD.
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LI Jian-shuang,CHEN Zhi-yun,HONG Wei. Effect of Vitamin E on the Expression of SIRT1 and PGC-1�� in Mice with Nonalcoholic Fatty Liver Disease. Chinese Pharmaceutical Journal, 2017, 52(12): 1029-1033.
DAY C P, J AMESOF W. Steatohepatitis: a tale of two hits[J].Gastroenterology, 1998, 114(4): 842-845.
[2]
IBRAHIM M A, KELLENI M, GEDDAWY A.Nonalcoholic fatty liver disease:current and potential therapies[J]. Life Sci, 2013, 92(2):114-118.
[3]
DADAMO E, MARCOVECCHIOML, GIANNINI C, et al.Improved oxidative strees and cardio-metabolic status in obese prepubertal children with liver steatosis treated with lifestyle combined with vitamin E[J]. Free Radic Res, 2013, 47(3):146-153.
[4]
FOSTER T, BUDOFF M J, SAAB S, et al. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial[J].Am J Gastroenterol, 2011, 106(1):71-77.
[5]
Fatty Liver and Alcoholic Liver Disease Study Group of Chinese Liver Disease Association. Diagnostic standard of nonalcoholic fatty disease (revised edition of 2010)[J]. Chin J Hepatol(�л����ಡ��־), 2010, 18(3):163-166.
[6]
XU L M, LIU P, LU G, et al. Alterations of collagen type I, IV and laminin in perisinusoids of fibrotic rat liver [J].Chin J Digest(���绪��������־),1995, 15(3):146-148.
[7]
WILLIAMS C D, STENGEL J, ASIKE M L, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middleaged population utilizing ultrasound and liver biopsy:a prospective study[J].Gastroenterology, 2011, 140 (1):124-131.
[8]
TAN M, TANG C, ZHANG Y, et al. SIRT1/PGC-1�� signaling protects hepatocytes against mitochondrial oxidative stress induced by bile acids[J]. Free Radic Res,2015, 49(8):935-945.
[9]
HONG Z, HAI L L, HUI M, et al. Effect of vitamin E supplement in diet on antioxidant ability of testis in Boer goat [J]. Anim Reprod Soi, 2010, 117(1-2):90-94.
[10]
SHEN F, DING X D, FAN J G. Brief introduction of practice guideline for the diagnosis and management of non-alcoholic fatty liver disease[J]. Chin J Front Med Sci(Elect Ver)(�й�ҽѧǰ����־���Ӱ�), 2012, 4(7):11-13.
[11]
LIU J H, ZHU F F, RUANG Y. Clinical study on rosiglitazone combined with vitamin E in the treatment of nonalcoholic fatty liver disease[J]. Med Innov China(�й�ҽѧ����), 2014, 11(7):60-63.
2017, Vol. 52 
