紫苏叶提取物通过AMPK/mTOR自噬信号通路改善糖尿病肾病大鼠肾脏损伤研究

Perilla Frutescens Leaf Extract Improves Renal Damage in Diabetic Nephropathy Rats via AMPK/mTOR Autophagy Signaling Pathway

目的:研究紫苏叶提取物在STZ诱导的大鼠糖尿病肾病(DN)中的治疗作用及相关分子机制。方法:取60只SD大鼠以随机数字表法分为空白对照组、模型组、紫苏叶提取物低剂量组(给予紫苏叶提取物200 mg/kg)、紫苏叶提取物高剂量组(给予紫苏叶提取物400 mg/kg)、厄贝沙坦组(给予厄贝沙坦13.5 mg/kg)共5组,每组12只,各给药组大鼠按照其分组进行给药干预7周,1次/d,空白对照组和模型组给予等量生理盐水。实验结束后收集大鼠血、尿及肾脏样本进行分析检测。结果:与模型组相比,紫苏叶提取物干预的糖尿病肾病模型大鼠体质量、24 h尿量、随机血糖、肾脏指数、24 h尿蛋白及肾小球局部纤维化病变得到明显改善(P<0.01),自噬信号通路相关蛋白Sesn2、LC3表达水平明显增加,p-mTOR/mTOR比值增加。结论:紫苏叶提取物能够改善DN模型大鼠肾小球局部损伤,其作用机制可能与Sesn2/AMPK/mTOR自噬信号通路有关。

Objective:To study the therapeutic effect and molecular mechanism of perilla frutescens leaf extract(PFLE)in STZ induced diabetic nephropathy(DN)in rats.Methods:60 SD rats were randomly divided into control group,model group,low dose group of PFLE(200 mg/kg),high dose group of PFLE(400 mg/kg),and irbesartan group(13.5 mg/kg),with 12 rats in each group.Rats were given intervention according to their grouping for 7 weeks,once a day.After the intervention,blood,urine and kidney samples were collected for analysis.Results:Compared with model group,the body weight,24 h urine volume,random blood glucose,kidney index,24 h urine protein and local glomerular fibrosis in the groups of PFLE intervention were significantly improved(P<0.01).The expression levels of Sesn2 and LC3,which are related to autophagy signaling pathway,significantly increased,and the ratio of p-mTOR/mTOR also increased.Conclusion:Perilla frutescens leaf extract improves local glomerular injury in DN model rats,and the mechanism may be related to Sesn2/AMPK/mTOR autophagy signaling pathway.