黄芪甲苷尾静脉注射对大鼠肾缺血再灌注损伤的干预作用及其机制
Intervention effect and mechanism of caudal vein injection of astragaloside Ⅳ on renal ischemia-reper-fusion injury in rats
杨开银 1李晓凤 1张国欣 2何炎鸿 1张凌云1
作者信息
- 1. 甘肃省中医院麻醉科,兰州 730000
- 2. 甘肃中医药大学基础医学院
- 折叠
摘要
目的 观察黄芪甲苷尾静脉注射对大鼠肾缺血再灌注损伤的干预作用,并基于PI3K/AKT信号通路及自噬调控探讨相关机制.方法 60只健康雄性SD大鼠随机分为黄芪甲苷组、渥曼青霉素组、模型组和对照组.黄芪甲苷组、渥曼青霉素组、模型组制作肾缺血再灌注损伤模型,对照组只游离双肾肾蒂并行右肾切除术,不进行其他处理;黄芪甲苷组于再灌注前5 min采用尾静脉注射黄芪甲苷10 mg/kg,渥曼青霉素组分别于再灌注前5、10 min依次注射10 mg/kg黄芪甲苷和0.6 mg/kg渥曼青霉素(PI3K特异性抑制剂),对照组和模型组于同时间点注射等容量生理盐水.再灌注24 h时检测血清肌酐(Cr)和尿素氮(BUN),取肾组织HE染色观察病理变化,观察肾组织细胞凋亡情况并计算凋亡指数,检测肾组织中的微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)、自噬效应蛋白Beclin-1和磷酸化AKT(p-AKT)蛋白.结果 黄芪甲苷组、渥曼青霉素组、模型组血清Cr、BUN水平高于对照组,模型组、渥曼青霉素组、黄芪甲苷组血清Cr、BUN水平依次降低(P均<0.05).黄芪甲苷组和渥曼青霉素组肾脏组织病理损伤较模型组有所减轻,其中黄芪甲苷组更为明显.黄芪甲苷组、渥曼青霉素组、模型组肾组织细胞凋亡指数和LC3-Ⅱ、Beclin-1、p-AKT蛋白表达高于对照组,模型组、渥曼青霉素组、黄芪甲苷组凋亡指数和LC3-Ⅱ、Beclin-1蛋白表达依次降低,渥曼青霉素组p-AKT蛋白表达低于黄芪甲苷组(P均<0.05).结论 黄芪甲苷干预可减轻大鼠肾缺血再灌注损伤,其机制可能与调控PI3K/AKT通路、抑制自噬有关.
Abstract
Objective To observe the intervention effect of caudal vein injection of astragaloside Ⅳ on renal isch-emia-reperfusion injury in rats,and to explore the related mechanism based on the regulation of PI3K/AKT signaling path-way and autophagy.Methods Sixty healthy male SD rats were randomly divided into the astragaloside Ⅳ group,wort-mannin group,model group,and control group,respectively.Ischemia-reperfusion injury models were made in the as-tragaloside Ⅳ group,wortmannin group and model group,while in the control group,we only dissociated the renal pedicle of both kidneys and underwent right nephrectomy without other treatment.Rats in the astragaloside Ⅳ group were injected with astragaloside Ⅳ 10 mg/kg at 5 min before reperfusion,while rats in the wortmannin group were injected with astraga-loside Ⅳ 10 mg/kg and wortmannin 0.6 mg/kg(PI3K specific inhibitor)at 5 min and 10 min before reperfusion,respec-tively.Rats in the control group and the model group were injected with equal volume of normal saline at the same time.Serum creatinine(Cr)and urea nitrogen(BUN)were detected at 24 h after reperfusion.Renal tissue was stained with HE to observe the pathological changes.We observed the apoptosis of renal cells and calculated the apoptosis index,and de-tected microtubule-associated protein light chain 3-Ⅱ(LC3),Beclin-1 and phosphorylated AKT(p-AKT)in renal tis-sues.Results The levels of serum Cr and BUN in the astragaloside Ⅳ group,wortmannin group and model group were higher than those in the control group,while the levels of serum Cr and BUN in the model group,wortmannin group and as-tragaloside Ⅳ group decreased in turn(all P<0.05).Compared with the model group,the pathological damage of renal tis-sue in the astragaloside Ⅳ group and wortmannin group was reduced,especially in the astragaloside Ⅳ group.Apoptosis index and the expression levels of LC3-Ⅱ,Beclin-1 and p-AKT protein in the renal tissues of the astragaloside Ⅳ group,wortmannin group and model group were higher than those in the control group,but the apoptosis index and the expression levels of LC3-Ⅱ and Beclin-1 protein in the model group,wortmannin group and astragaloside Ⅳ group decreased in turn,and the expression of p-AKT protein in wortmannin group was lower than that in astragaloside Ⅳ group(all P<0.05).Conclusion Astragaloside Ⅳ intervention can alleviate renal ischemia-reperfusion injury in rats,and its mechanism may be related to regulating PI3K/AKT pathway and inhibiting autophagy.
关键词
黄芪甲苷/肾缺血再灌注损伤/PI3K/AKT通路/自噬Key words
astragaloside Ⅳ/renal ischemia-reperfusion injury/PI3K/AKT pathway/autophagy引用本文复制引用
基金项目
甘肃省自然科学基金项目(20JR5RA159)
出版年
2024
国家科技期刊平台
NSTL
万方数据