轻断食对高脂高胆固醇诱导的非酒精性脂肪性肝炎大鼠焦亡的影响

Effect of Intermittent Fasting on Pyroptosis with Non-Alcoholic Steatohepatitis Induced by High Fat and High Cholesterol in Rats

该实验旨在研究轻断食对高脂高胆固醇诱导的非酒精性脂肪肝大鼠焦亡的影响。该研究将SD大鼠随机分为正常饮食饲喂的对照组、高脂高胆固醇饲喂诱导非酒精性脂肪肝炎模型组以及其相对应的轻断食组,饲喂16周后,收集大鼠腹主动脉血浆和肝脏标本,检测血浆ALT与AST的活性;检测肝脏总胆固醇(total cholesterol,TC)与甘油三酯(triglyceride,TG)的含量;HE和Masson三色染色观察肝脏病理变化;Western blot与qRT-PCR检测各组肝脏组织焦亡相关蛋白与基因半胱氨酸天冬氨酸蛋白水解酶1(Caspase-1)、消化道皮肤素D(gasdermin D,GSDMD)和白细胞介素-1β(interleukin-1beta,IL-1β)的表达。与对照组相比,模型组肝细胞脂肪变性明显,出现纤维沉积,血浆ALT、AST和肝脏TC、TG含量明显升高,焦亡相关蛋白与基因Caspase-1、GSDMD和IL-1β含量明显升高(P<0.05);与模型组相比,轻断食组细胞脂肪变性显著减轻,无大量纤维沉积,血浆ALT、AST和肝脏TC、TG含量明显降低,焦亡相关蛋白与基因Caspase-1、GSDMD和IL-1β含量明显降低(P<0.05)。实验表明,轻断食可能通过抑制Caspase-1、GSDMD和IL-1β介导的细胞焦亡而改善非酒精性脂肪性肝炎。

The aim of this study was to investigate the effect of intermittent fasting on pyroptosis in rats with non-alcoholic steatohepatitis.SD rats were randomly divided into the control group,high-fat and high-cholesterol-fed NASH model group and intermittent fasting group.Plasma and liver samples were collected to detect the activities of ALT,AST,TC and TG after 16 weeks.The pathological changes of liver were observed by HE and Masson staining.The expression of pyroptosis-related proteins and genes such as Caspase-1,GSDMD and IL-1β in liver tissues were detected by Western blot and qRT-PCR.Compared with the control group,hepatocyte steatosis and fiber deposition were observed in the NASH model group.Compared with the control group,the contents of ALT,AST,TC and TG in NASH model group were significantly increased,and the contents of proteins and genes of Caspase-1,GSDMD and IL-1β were significantly increased (P<0.05).By contrast with NASH model group,hepatocytes steatosis and fibrous deposition were visibly reduced in the intermittent fasting group.Different from the NASH model group,the contents of ALT,AST in plasma and TC and TG in liver of rats were significantly reduced,and the contents of proteins and genes of Caspase-1,GSDMD and IL-1β were decreased in the intermittent fasting group (P<0.05).Experimental investigation showed that intermittent fasting might alleviate the occurrence and development of nonalcoholic steatohepatitis by inhibiting hepatocyte pyroptosis mediated by Caspase-1,GSDMD and IL-1β.