文献类型：期刊文献

中文题名：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

英文题名：Intervention effect and mechanism of caudal vein injection of astragaloside Ⅳ on renal ischemia-reper?fusion injury in rats

作者：杨开银[1];李晓凤[1];张国欣[2];何炎鸿[1];张凌云[1]

第一作者：杨开银

机构：[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

第一机构：甘肃省中医院麻醉科,兰州730000

年份：2024

卷号：64

期号：20

起止页码：35

中文期刊名：山东医药

外文期刊名：Shandong Medical Journal

收录：CSTPCD

基金：甘肃省自然科学基金项目(20JR5RA159)。

语种：中文

中文关键词：黄芪甲苷;肾缺血再灌注损伤;PI3K/AKT通路;自噬

外文关键词：astragalosideⅣ;renal ischemia-reperfusion injury;PI3K/AKT pathway;autophagy

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。
Objective To observe the intervention effect of caudal vein injection of astragalosideⅣon 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 astragalosideⅣgroup,wort-mannin group,model group,and control group,respectively.Ischemia-reperfusion injury models were made in the as-tragalosideⅣgroup,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 astragalosideⅣgroup were injected with astragalosideⅣ10 mg/kg at 5 min before reperfusion,while rats in the wortmannin group were injected with astraga-losideⅣ10 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 astragalosideⅣgroup,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-tragalosideⅣgroup decreased in turn(all P<0.05).Compared with the model group,the pathological damage of renal tis-sue in the astragalosideⅣgroup and wortmannin group was reduced,especially in the astragalosideⅣgroup.Apoptosis index and the expression levels of LC3-Ⅱ,Beclin-1 and p-AKT protein in the renal tissues of the astragalosideⅣgroup,wortmannin group and model group were higher than those in the control group,but the apoptosis index and the expression levels of LC3-Ⅱand Beclin-1 protein in the model group,wortmannin group and astragalosideⅣgroup decreased in turn,and the expression of p-AKT protein in wortmannin group was lower than that in astragalosideⅣgroup(all P<0.05).Conclusion AstragalosideⅣintervention can alleviate renal ischemia-reperfusion injury in rats,and its mechanism may be related to regulating PI3K/AKT pathway and inhibiting autophagy.