黄芪甲苷对被动型Heymann肾炎大鼠PERK通路的影响  

Astragaloside IV Has Effect on PERK Pathway in Rats with Passive Heymann Nephritis

作　　者：项协隆 邵思思 陈宇 陈春 董飞侠 XIANG Xielong;SHAO Sisi;CHEN Yu;Chen Chun;Dong Feixia

机构地区：[1]浙江中医药大学附属温州中医院肾内科,浙江温州325000 [2]温州老年病医院,浙江温州325000

出　　处：《新中医》2018年第4期10-14,共5页New Chinese Medicine

基　　金：温州市科技计划项目(Y20160308)

摘　　要：目的:观察黄芪甲苷对被动型Heymann肾炎大鼠PERK通路的影响。方法:用羊抗大鼠Fx1A抗体血清尾静脉注射制备被动型Heymann肾炎大鼠模型。40只SD大鼠随机分为正常对照组、模型组、黄芪甲苷低剂量组、黄芪甲苷高剂量组和贝那普利组。造模成功后各治疗组灌胃给药4周。定期检测24 h尿蛋白定量。4周后处死所有大鼠,采血检测血清白蛋白,PASM染色观察肾组织病理学改变,免疫组化检测肾组织磷酸化蛋白激酶R样内质网激酶(p-PERK)、磷酸化真核细胞翻译起始因子2α(p-e IF2α)的表达,Western blot检测肾组织中葡萄糖调节蛋白78(GRP78)的表达。结果:模型组大鼠24 h尿蛋白定量较正常对照组显著升高(P<0.05),并随着时间推移蛋白尿逐渐增多,至4周后达到高峰。在给药4周后,与正常对照组比较,模型组大鼠肾组织p-PERK、p-e IF2α、GRP78表达明显升高,血清白蛋白明显降低,差异均有统计学意义(P<0.05)。与模型组比较,黄芪甲苷高剂量组及贝那普利组大鼠24 h尿蛋白显著减少,肾组织p-PERK、p-e IF2α、GRP78表达显著减少,血清白蛋白显著升高,差异均有统计学意义(P<0.05)。结论:黄芪甲苷可能通过抑制内质网应激(ERS)中的PERK通路缓解被动型Heymann肾炎大鼠肾脏损伤。Objective：To observe the effect of astragaloside IV on PERK pathway in rats with passive Heymann nephritis.Methods：The rat model of passive Heymann nephritis was established by tail intravenous injection of anti-Fx1 A serum.Forty SD rats were randomly divided into the normal control group,the model group,the low-dose astragaloside IV group,the high-dose astragaloside IV group and the benazepril group.After the success of model establishment,each treatment group received intragastric administration for 4 weeks.Detected 24-h urinary protein quantification periodically.After 4 weeks,sacrificed all the rats,collected blood to detect serum albumin,observed the renal pathological changes by PASM,detected the expression of phosphorylated protein kinase R-like ER kinase（p-PERK）and phosphorylated eukaryotic translation initiation factor 2α（p-eIF2α）in renal tissues by immunehistochemistry,and detected the expression of glucose-regulated protein 78（GRP78）in renal tissues by Western blot.Results：24-h urinary protein quantification of rats in the model group was significantly higher than that in the normal control group（P 0.05）,and the urine protein was gradually increased as time went by,which reached its peak after 4 weeks.After administration for 4 weeks,comparing with the normal control group,the expression of p-PERK,p-eIF2α and GRP78 in the renal tissues of rats in the model group was evidently higher,serum albumin was decreased evidently,differences being significant（P 0.05）.Comparing with the model group,24-h urinary protein quantification of rats in the high-dose astragaloside IV group and the benazepril group were significantly decreased,the expression of p-PERK,p-eIF2α and GRP78 in the renal tissues was significantly decreased,and serum albumin was significantly increased,differences being significant（P 0.05）.Conclusion：Astragaloside IV may relieve the renal damage resulting from passive Heymann nephritison by inhibiting PERK pathway in endoplasmic reticulum stress（ERS）.

关 键 词：黄芪甲苷 HEYMANN肾炎 内质网应激(ERS) 膜性肾病 动物实验 大鼠 

分 类 号：R692.3[医药卫生—泌尿科学]