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作 者:章怡祎[1] 刘宇[1] 顾仁樾[1] 王国印[1] 杨建梅[2]
机构地区:[1]上海中医药大学附属龙华医院,上海200032 [2]上海市徐汇区中心医院,上海200031
出 处:《中华高血压杂志》2009年第1期45-49,共5页Chinese Journal of Hypertension
基 金:上海市教委资助项目(基金编号:07cz07)
摘 要:目的观察白蒺藜有效组分对自发性高血压大鼠(SHR)肾骨形态发生蛋白(BMP)/Smads信号通路的影响。方法14周龄雄性SHR 32只随机分为未治疗SHR组(n=8)、卡托普利组[30 mg/(kg.d),n=8]、白蒺藜组[15 mg/(kg.d),n=8]、联用组[白蒺藜有效组分15 mg/(kg.d)+卡托普利30 mg/(kg.d),n=8],同周龄雄性WKY大鼠8只作为正常对照。未治疗SHR组及正常组给生理盐水2 mL/(只.d)灌胃。8周后,测定各组大鼠收缩压;VG染色观察肾组织病理改变;Western-blot方法检测肾BMP7、Smad5、Smad6蛋白表达水平。结果经治疗后,各用药组SHR收缩压均明显下降[未治疗SHR组(226±6)比WKY组(141±13)mmHg,P<0.01;比白蒺藜组(209±7)、卡托普利组(179±8)、联用组(170±4)mmHg,P<0.01]。肾组织病理结果表明各用药组SHR肾纤维化程度较未治疗SHR明显减轻。未治疗SHR组肾BMP7、Smad5表达降低,Smad6表达增高。白蒺藜有效组分可明显下调肾Smad6表达(0.502±0.131 vs未治疗SHR:0.959±0.099,P<0.01),卡托普利及二药联用明显上调肾BMP7(卡托普利:0.454±0.041,联用组:0.615±0.252 vs未治疗SHR:0.181±0.063,P<0.01)及Smad5(卡托普利:0.819±0.077,联用组:0.850±0.069 vs未治疗SHR:0.428±0.038,P<0.01)表达、同时下调Smad6(卡托普利:0.720±0.104,联用组:0.631±0.041 vs未治疗SHR:0.959±0.099,P<0.01)水平。结论白蒺藜有效组分可能通过对BMP/Smads通路的调控改善高血压肾纤维化。Objective To study the effect of tribulus-terrestris-L on renal BMP/Smads in spontaneously hy- pertensive rat (SHR). Methods Thirty-two 14-week-old male SHRs were randomized to receive following approaches: placebo (normal saline 2 mL, n=8), captopril [30 mg/kg· d), n=8], tribulus-terrestris-L 115 mg/kg, d, n=8) and combined treatment (captopril 30 mg/(kg · d) plus tribulus-terrestris-L 15 mg/ (kg· d), n=8]. 14- week-old male WKY rats ( n= 8 ) were used as control. Renal BMP7, smad5 and smad6 were measured by Western blot; renal tissues by light microscopy after 8 weeks' treatment. Results Compared with placebo group, SBP were significant decreased by tribulus-terrestris-L ( placebo: 226 ± 6 vs tribulus-terrestris-L group 209 ± 7 mmHg), captopril (placebo: 226±6 vs 179±8 mmHg, P〈0.01) and combined treatment (placebo: 226±6 vs 170±4 mmHg, P〈 0.01); tribulus-terrestris-L, captopirl and combined treatment all alleviated renal fibrosis. Renal BMP7, smad5 levels were decreased, while smad6 level was increased in SHRs. Tribulus-terrestris-L monotherapy markedly decreases renal smad6 (0. 502±0. 131) expression. Both tribulus-terrestis and combined treatment increased BMP7 (captopril: 0. 454±0. 041, combined treatment: 0. 615 ± 0. 252 vs placebo: 0. 181 ± 0. 063, both P〈0.01 ) and smad5 ( captopril: 0.819 ± 0. 077, combined treatment : 0. 850 ± 0. 069 vs placebo : 0. 428 ± 0. 038, both P〈 0.01) expressions associated with decreases in smad6 ( captopril: 0. 720 ± 0. 104, combined treatment : 0. 631 ± 0. 041 vs placebo: 0. 959±0. 099, both P〈0.01). Conclusion This study shows that tribulus-terrestris-L exert an inhibitory effect on renal fibrosis, and such effect may be related to regulating of BMP/smads signaling pathway.
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