Pitavastatin inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model rats
Pitavastatin inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model rats
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DOI：
10.1111/j.1872-034x.2010.00769.x
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Joh, Takashi
中科院分区：
文献类型：
--
作者：
Miyaki, Tomokatsu;Nojiri, Shunsuke;Joh, Takashi
目的：非酒精性脂肪性肝炎（NASH）可能进展为肝硬化，NASH合并肝硬化的患者有发展为肝细胞癌的风险。他汀类药物是 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂，众所周知可降低低密度脂蛋白胆固醇，并通过抗炎和抗纤维化作用降低冠心病和其他主要血管事件的发生率，并且还报道了其在结直肠癌中的抗增殖特性。最近，有报道称他汀类药物可以改善肝脂肪变性；方法：使用缺乏胆碱的左旋氨基酸（CDAA）饮食肝纤维化模型检查匹伐他汀（最强的他汀类药物之一）的作用。结果：匹伐他汀显着减弱血清天冬氨酸转氨酶、丙氨酸转氨酶、肝脂肪变性、氧化应激、肿瘤前病变（胎盘谷胱甘肽 S-转移酶）的升高。形成阳性病变），细胞因子的表达，如肿瘤坏死因子-α和转化生长因子-β1，以及金属蛋白酶-1组织抑制剂、金属蛋白酶-2组织抑制剂和I型前胶原基因的表达，从而减轻CDAA喂养大鼠的肝脏纤维化。结论：这些结果表明，匹伐他汀可以抑制NASH大鼠模型中的脂肪变性、肝纤维化和癌变。
Aim:Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors, are well known to reduce low-density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti-inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial.Methods:The effects of pitavastatin (one of the strongest statins) were examined using a choline-deficient L-amino acid-defined (CDAA) diet liver fibrosis model.Results:Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre-neoplastic lesions (glutathione S-transferase placental form-positive lesions), expression of cytokines, such as tumor necrosis factor-alpha and transforming growth factor-beta 1, and the expression of tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA-fed rats.Conclusion:These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH.