淫羊藿苷抗自发性高血压大鼠肾小管上皮细胞凋亡的作用  

Anti-apoptotic effect of Icariin on renal tubular epithelial cell in SHR

作　　者：朱玲[1] 王颖婉 李叶丽 钱志强[1] 杨华[2] 杨丹莉[1] 

机构地区：[1]遵义医学院药理学教研室暨基础药理省部共建教育部重点实验室 [2]遵义医学院附属医院病理科,贵州遵义563000

出　　处：《中国药理学通报》2016年第4期537-541,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学专项基金(No81241142)

摘　　要：目的观察淫羊藿苷(icariin,Ica)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾小管上皮细胞凋亡的影响,探讨其可能的机制。方法将21只14周龄♂SHR随机分为模型组,Ica低、高剂量组(20、40 mg·kg-1,ig,bid,至26周龄),14周龄♂同源京都大鼠(WKY)为对照组,各组动物数均为7只。WKY组、模型组同期灌胃等体积双蒸水。采用HE染色观察肾脏病理学变化;原位缺口末端标记法检测肾小管上皮细胞凋亡;real time RT-PCR法检测肾Bok、Bcl-2、Bax mRNA水平;Western blot法检测肾Bcl-2、Bax、Active caspase-3蛋白表达。结果与WKY组相比,模型组肾小球囊腔狭窄且不规则,肾小球系膜基质增多,细胞排列紊乱,毛细血管扩张充血,个别肾小球出现皱缩,肾小管上皮细胞水肿、管腔狭窄;肾小管上皮细胞凋亡明显,Bok和Bax mRNA水平、Bax和Active caspase-3蛋白表达均明显上调,Bcl-2 mRNA和蛋白的水平明显下调(P<0.05或P<0.01)。与模型组比较,Ica-L组、Ica-H组肾小球囊腔增宽,肾小球系膜基质增生减少,细胞排列紊乱有所改善,毛细血管扩张充血、肾小管管腔狭窄均减轻;肾小管上皮细胞凋亡以及Bok、Bax mRNA水平和Bax蛋白表达均明显下调,IcaH组肾Bcl-2 mRNA水平和蛋白表达明显上调,Active caspase-3蛋白表达明显下调(P<0.05或P<0.01)。结论淫羊藿苷可抑制SHR肾小管上皮细胞凋亡,其机制可能与下调Bax、Active caspase-3、Bok,上调Bcl-2表达有关。Aims To observe the effect of Icariin( Ica)on apoptosis of renal tubular epithelial cell in spontaneously hypertensive rats( SHR),and to explore its possible mechanism. Methods 21 male SHR of 14 weeks were randomly divided into model groups,the Ica low and high dose groups( 20 or 40 mg·kg- 1,ig,bid,to26 weeks),14 week-old male homologous Kyoto rats( WKY) as control group,and the number of each group was 7. WKY group and model group were administered by gavage with the same volume of double distilled water. The pathological changes were observed by using the HE staining and the apoptosis was detected by TUNEL method in renal tubular epithelial cell,respectively. The mRNA levels of Bok,Bax,Bcl-2were detected by the real time RT-PCR and the protein expressions of Bcl-2,Bax and Active caspase-3 were detected by Western blot method in the renal tissue.Results Compared with WKY,renal capsule was narrow and irregular,and glomerular mesangial matrix was increased with the cell arrangement disorder and the capillary dilation and congestion. Several glomeruli shrank and renal tubular epithelial cell was edema with luminal stenosis in model group. The apoptosis of renal tubular epithelial cell was evident and the mRNA levels of Bok and Bax,as well as the protein expressions of Bax and Active caspase-3 were significantly up-regulated in model group,while the mRNA Level and protein expression of Bcl-2 significantly down-regulated( P <0. 05 or P < 0. 01). Compared with model group,renal glomerular capsule widened,proliferation of glomerular mesangial matrix was reduced,and cell arrangement disorder and capillary dilation and renal tubular lumen stenosis were improved in Ica group. Renal tubular epithelial cell apoptosis was decreased evidently,and the mRNA level of Bax,Bok and protein expression of Bax were significantly down-regulated in Ica group,and the mRNA level and protein expression of Bcl-2 in Ica-H group were significantly up-regulated while the protein expression of Active caspase-3 significantly down-regulated( P <

关 键 词：淫羊藿苷 自发性高血压大鼠 凋亡 BCL-2 BAX Ac-tive CASPASE-3 

分 类 号：R-332[医药卫生] R284.1