盐酸埃他卡林对自发性高血压大鼠肾组织细胞外基质降解系统的影响

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (10): 1122-1128.

盐酸埃他卡林对自发性高血压大鼠肾组织细胞外基质降解系统的影响

薛浩¹, 高敏, 刘国树¹, 汪海

军事医学科学院毒物药物研究所, 北京 100037;
¹解放军总医院南楼心内科, 北京 100037

收稿日期:2006-04-19 修回日期:2006-06-20 出版日期:2006-10-26 发布日期:2020-11-05
通讯作者: 汪海, 男, 博士, 研究员, 博士生导师, 从事心血管药理和新药研究工作。Tel:010-66932651 E-mail:wh9588@yahoo.com.cn
作者简介:薛浩, 女, 医学博士, 副主任医师, 研究方向:心血管内科学。Tel:010-88398702 　E-mail:xh950216@163.com
基金资助:
国家863 计划重大专项(No2002AA2Z3137)

Effect of iptakalim hydrochloride on extracellular matrix of kidney in spontaneously hypertensive rats

XUE Hao¹, GAO Min, LIU Guo-shu¹, WANG Hai

Institute of Pharmacology and Toxicology, Academy of Millitary Medical Sciences, Beijing 100850 , China;
¹Department of Cardiology, General Hospital of PLA, Beijing 100853 , China

Received:2006-04-19 Revised:2006-06-20 Online:2006-10-26 Published:2020-11-05

摘要/Abstract

摘要： 目的观察埃他卡林(iptakalim hydrochloride,Ipt) 对自发性高血压大鼠(spontaneously hyper-tensive rats, SHR) 肾组织细胞外基质降解系统的影响。方法 SHR 于第12 周龄进入实验, 实验分组如下:Ipt1 、3 、9 mg·kg^-1 ·d^-1 剂量组, 苯那普利(benazepril)3 mg·kg^-1·d^-1治疗组及SHR 空白对照组, 另设同月龄同种属正常血压大鼠(Wistar Kyoto rat, WKY) 为正常对照组, 灌胃给药每天1次, 持续给药12 周,应用免疫组织化学和RT-PCR 技术, 观察埃他卡林对高血压大鼠肾组织Ⅳ型胶原(Col-Ⅳ) 、转化生长因子β1 (TGF-β1) 、基质金属蛋白酶(MMPs) 及其抑制物(TIMPs) 表达的影响。结果埃他卡林长期降压治疗同时上调肾组织局部MMP-9/mRNA 和蛋白水平,同时一致性降低TIMP-1 、TGF-β1 及Ⅳ型胶原转录和蛋白水平。结论埃他卡林对肾脏靶器官的保护作用机制可能通过抑制肾脏局部TGF-β1 表达, 纠正MMP-9 TIMP-1 失衡, 从而促进细胞外基质的降解,减少细胞外基质的积聚。

关键词: 盐酸埃他卡林, 自发性高血压大鼠, 肾脏, 细胞外基质

Abstract: AIM: To investigate the effects of iptakalim hydrochloride (Ipt) on extracellular matrix in SHR renal tissue.METHODS: SHRs at the age of 12-week-old were treated ig with Ipt 1, 3, 9mg·kg^-1·d^-1 ,benazepril 3 mg·kg^-1·d^-1 once a day for 12 weeks.Age-matched WKY rats were used as normal control.The effects of iptakalim on collagen-Ⅳ, MMP-9, TIMP-1 and TGF-β1 expression in SHR kidneys were measured by immunohistochemistry and RT-PCR.RESULTS: After 12 weeks treatment with iptakalim, the expression of MMP-9 mRNA and protein were up-regulated, and those of TGF-β1 , TIMP-1, and Col-Ⅳwere down-regulated in the SHR kidney compared with the untreated controls.CONCLUSION: Iptakalim protects the kidney from hypertensive damage partly by inhibiting TGF-β1 expression and regulating MMP-9 TIMP-1 unbalance in renal tissue, thus promoting ECM degradation, decreasing ECMaccumulation.

Key words: iptakalim hydrochloride, spontaneously hypertensive rats, kidney, extracellular matrix

中图分类号:

薛浩, 高敏, 刘国树, 汪海. 盐酸埃他卡林对自发性高血压大鼠肾组织细胞外基质降解系统的影响[J]. 中国临床药理学与治疗学, 2006, 11(10): 1122-1128.

XUE Hao, GAO Min, LIU Guo-shu, WANG Hai. Effect of iptakalim hydrochloride on extracellular matrix of kidney in spontaneously hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1122-1128.

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