METHODS: C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines.
RESULTS: Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels.
CONCLUSIONS: In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.
方法:C57BL/6N小鼠饲喂Gubra-AmylinNASH(GAN)饮食20周以诱导NASH。曲尼司特组口服曲尼司特,剂量为300、400和500mg/kg/天,每周五天,共20周,除了GAN饮食。曲尼司特的效果是根据食物摄入的剂量来评估的,体重的变化,肝脏重量,血液生化参数,组织病理学检查,TRPV2和炎性细胞因子的表达。
结果:在GAN喂养的NASH小鼠模型中观察到肝脏中TRPV2的表达。曲尼司特组显示出体重和肝脏重量的显着抑制增加。肝内脂肪沉积和肝纤维化的发展,组织病理学评估,被抑制了。曲尼司特给药进步了肝脏中TRPV2和炎性细胞因子的表达。此外,血液检查表明肝酶水平升高降低。
结论:在GAN饮食NASH模型中,TRPV2在肝脏中上调,曲尼司特抑制TRPV2并抑制纤维化。因此,它可能预防与NASH相关的肝细胞癌的发生。