热量限制对肾缺血损伤后纤维化的影响及机制研究

Effect and mechanism of caloric restriction on fibrosis progression after renal ischemia injury

目的:探讨热量限制(CR)在肾脏缺血再灌注损伤(IRI)后纤维化进展中的作用及机制。方法:构建小鼠单侧肾脏缺血再灌注纤维化模型。随机分为假手术组、假手术后CR组、IRI组、IRI-CR组。术后第3天,CR组小鼠限时喂食,每日饮食摄入量为正常水平的66%,对照组小鼠术后持续自由饮食,所有组均自由饮水。每天限食时观察并记录各组老鼠一般状态。再灌注第20天切除右肾,24 h后采血并留取肾组织。检测血清肌酐、尿素氮及相关实验分析。结果:CR组肾纤维化较重;CR增强了IRI后肾小管细胞自噬活性;抑制自噬可显著减轻CR对IRI后纤维化的影响。结论:CR可加重肾脏IRI后的肾纤维化进展,其机制可能是通过激活自噬实现的。

Objective:To investigate the effect and mechanism of caloric restriction on the progression of renal ischemic fibrosis.Methodology:Unilateral renal ischemia reperfusion fibrosis model was established in mice.They were randomly divided into sham-operated group,sham-operated caloric restriction group,ischemia-reperfusion group,and ischemia-reperfusion caloric restriction group.On the third day after surgery,the mice in the caloric restriction group were fed for a limited time,and the daily dietary intake was 66%of the normal level.The mice in the control group continued to eat freely after ischemic surgery,and all groups drank freely.The state of rats in each group was observed and recorded during the diet.The right kidney was excised 20 days after reperfusion,and blood was collected 24 hours later and kidney tissue was retained.Serum creatinine,urea nitrogen and pathological examination were detected for experimental analysis.Results:Caloric restriction aggravated renal ischemic fibrosis.Caloric restriction enhances the autophagy activity after renal ischemia.The effect of caloric restriction on renal ischemic fibrosis was significantly weakened after autophagy was inhibited.Conclusion:Caloric restriction after renal ischemia can aggravate renal fibrosis by activating autophagy.