Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka 565-0871, Japan.
Mol Med Rep. 2012 Jan;5(1):37-40. doi: 10.3892/mmr.2011.594. Epub 2011 Sep 21.
Recent reports have shown that nifedipine, a calcium channel blocker, increases peroxisome proliferator-activated receptor-γ (PPARγ) activity. Since PPARγ agonists, such as pioglitazone and rosiglitazone, are effective in reducing non-alcoholic steatohepatitis (NASH) and cirrhosis in animal models, we examined the protective effects of nifedipine, as compared with bezafibrate, a PPARα agonist, in a NASH model induced by an L-methionine- and choline-deficient (MCD) diet. An MCD diet for 20 weeks changed the color of the rat liver to yellow with an irregular surface, whereas the color of the liver in both the bezafibrate and nifedipine treatment groups was markedly changed to yellow-brown with a smooth surface. Furthermore, nifedipine, as well as bezafibrate, significantly prevented liver fibrosis induced by an MCD diet, as assessed by Masson's trichrome staining, accompanied by a significant decrease in serum AST. Overall, nifedipine treatment resulted in an improvement in NASH, similar to bezafibrate, in a rat model. In hypertensive patients with metabolic syndrome, nifedipine may provide additional benefits, beyond its blood pressure-lowering effects, to prevent NASH and fatty liver disease.
最近的报告表明,钙通道阻滞剂硝苯地平可增加过氧化物酶体增殖物激活受体-γ(PPARγ)的活性。由于 PPARγ 激动剂,如吡格列酮和罗格列酮,在动物模型中可有效减少非酒精性脂肪性肝炎(NASH)和肝硬化,因此我们研究了硝苯地平(一种 PPARα 激动剂)与 bezafibrate 相比在 L-蛋氨酸和胆碱缺乏(MCD)饮食诱导的 NASH 模型中的保护作用。MCD 饮食 20 周可使大鼠肝脏颜色变为黄色,表面不规则,而 bezafibrate 和硝苯地平治疗组的肝脏颜色明显变为黄棕色,表面光滑。此外,硝苯地平与 bezafibrate 一样,可显著预防 MCD 饮食引起的肝纤维化,Masson 三色染色评估结果表明,血清 AST 显著降低。总的来说,硝苯地平治疗可改善 NASH,在大鼠模型中与 bezafibrate 相似。对于患有代谢综合征的高血压患者,硝苯地平除了降压作用外,可能还会提供额外的益处,以预防 NASH 和脂肪肝疾病。