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  

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

作　　者：薛浩[1] 高敏[2] 刘国树[1] 汪海[2] 

机构地区：[1]解放军总医院南楼心内科,北京100037 [2]军事医学科学院毒物药物研究所,北京100037

出　　处：《中国临床药理学与治疗学》2006年第10期1122-1128,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家863计划重大专项(№2002AA2Z3137)

摘　　要：目的观察埃他卡林(iptakalim hydrochloride,Ipt)对自发性高血压大鼠(spontaneously hyper-tensiverats,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、9mg·kg-1·d-1剂量组,苯那普利(benazepril)3mg·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 Kyotorat,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-9mRNA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。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, 9 mg·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-IV were 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.

关 键 词：盐酸埃他卡林 自发性高血压大鼠 肾脏 细胞外基质 

分 类 号：R965.2[医药卫生—药理学] R972.4[医药卫生—药学]