染料木黄酮在实验性非酒精性脂肪性肝炎模型中的预防作用。
Preventive role of genistein in an experimental non-alcoholic steatohepatitis model.
作者信息
Yalniz Mehmet, Bahcecioglu Ibrahim Halil, Kuzu Nalan, Poyrazoglu Orhan Kursat, Bulmus Ozgur, Celebi Selman, Ustundag Bilal, Ozercan Ibrahim Hanefi, Sahin Kazim
机构信息
Division of Gastroenterology, Firat University School of Medicine, Elazig, Turkey.
出版信息
J Gastroenterol Hepatol. 2007 Nov;22(11):2009-14. doi: 10.1111/j.1440-1746.2006.04681.x.
BACKGROUND AND AIM
The aim of the present study was to evaluate the preventive role of genistein, a phytoestrogen with a wide variety of pharmacological effects, in an experimental non-alcoholic steatohepatitis (NASH) model.
METHODS
Thirty-six Sprague-Dawley rats were divided into three groups. Group 1 (control) received only a standard rat diet, group 2 (placebo) was given a high fat diet (HFD) plus 0.5 mL/day saline subcutaneously, and group 3 (genistein group) a HFD plus subcutaneous genistein injection at dose of 0.2 mg/kg/day for 6 weeks. All rats were killed after 6 weeks. Serum aminotransferases, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and plasma and liver malondialdehyde (MDA) levels were measured. Additionally, steatosis, ballooning degeneration and inflammation of the liver were examined histopathologically.
RESULTS
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.001 for each), plasma and liver tissue MDA and plasma TNF-alpha levels (P < 0.001, <0.001, <0.01, respectively) were found to be higher in the placebo group than in the control group. TGF-beta levels, however, were comparable in the placebo and control groups (P > 0.05). Histopathologically, steatosis, inflammatory cells per mm(2) and ballooning degeneration were significantly higher in the placebo group than in the control group (P < 0.001 for each). Nevertheless, AST and ALT (P < 0.05 for each), plasma and liver tissue MDA (P < 0.05 for each) and plasma TNF-alpha levels (P < 0.001) were significantly decreased in the genistein group compared to the placebo group. Histopathologically, steatosis (P < 0.05), inflammatory cells per mm(2) and ballooning degeneration (P < 0.01 for each) in the genistein group were also significantly lower than in the placebo group.
CONCLUSIONS
Genistein, a strong antioxidant agent, significantly decreased the plasma TNF-alpha level and remarkably prevented the emergence of NASH by improving the biochemical and histopathological abnormalities via attenuating oxidative stress.
背景与目的
本研究旨在评估金雀异黄素（一种具有多种药理作用的植物雌激素）在实验性非酒精性脂肪性肝炎（NASH）模型中的预防作用。
方法
将36只Sprague-Dawley大鼠分为三组。第1组（对照组）仅给予标准大鼠饮食，第2组（安慰剂组）给予高脂饮食（HFD）并皮下注射0.5 mL/天生理盐水，第3组（金雀异黄素组）给予HFD并皮下注射剂量为0.2 mg/kg/天的金雀异黄素，持续6周。6周后处死所有大鼠。检测血清转氨酶、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β以及血浆和肝脏丙二醛（MDA）水平。此外，对肝脏的脂肪变性、气球样变性和炎症进行组织病理学检查。
结果
发现安慰剂组的天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）（各P < 0.001）、血浆和肝脏组织MDA以及血浆TNF-α水平（分别为P < 0.001、<0.001、<0.01）均高于对照组。然而，安慰剂组和对照组的TGF-β水平相当（P > 0.05）。组织病理学检查显示，安慰剂组的脂肪变性、每平方毫米炎症细胞数和气球样变性均显著高于对照组（各P < 0.001）。不过，与安慰剂组相比，金雀异黄素组的AST和ALT（各P < 0.05）、血浆和肝脏组织MDA（各P < 0.05）以及血浆TNF-α水平（P < 0.001）均显著降低。组织病理学检查还显示，金雀异黄素组的脂肪变性（P < 0.05）、每平方毫米炎症细胞数和气球样变性（各P < 0.01）也显著低于安慰剂组。
结论
金雀异黄素作为一种强抗氧化剂，通过减轻氧化应激改善生化和组织病理学异常，显著降低血浆TNF-α水平，并明显预防了NASH的出现。
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