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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 observe the effect of effective components of Radix Paeoniae Alba on the bone resorption protein (BMP)/Smads signaling pathway in spontaneously hypertensive rats (SHR). Methods Thirty-four male SHRs aged 14 weeks were randomly divided into untreated SHR group (n=8), captopril group [30 mg/(kg.d), n=8] and Baizhi group [15 mg/(kg). .d), n=8], combination group [15 mg/(kg.d) + captopril 30 mg/(kg.d), n=8], same age male WKY Eight rats served as normal controls. Untreated SHR and normal groups were given intragastric administration of normal saline 2 mL/(only for d). After 8 weeks, the systolic blood pressure was measured in each group; pathological changes of renal tissue were observed by VG staining; and the expression levels of BMP7, Smad5, and Smad6 proteins were detected by Western-blot. Results After treatment, SHR systolic blood pressure decreased significantly in each drug group (226±6 in untreated SHR group compared with WKY group (141±13) mmHg, P<0.01; compared with white peony group, 209±7), Cato Puli group (179 ± 8), combined group (170 ± 4) mmHg, P <0.01]. The pathological results of renal tissue showed that the degree of renal fibrosis in all treatment groups was significantly less than that of untreated SHR. In the untreated SHR group, the expression of BMP7 and Smad5 decreased, and the expression of Smad6 increased. The effective components of Angelica sinensis could significantly down-regulate the expression of renal Smad6 (0.502±0.131 vs. untreated SHR: 0.959±0.099, P<0.01), and captopril and two drugs combined to significantly up-regulate renal BMP7 (captopril: 0.454± 0.041, Combined group: 0.615±0.252 vs. untreated SHR: 0.181±0.063, P<0.01) and Smad5 (captopril: 0.819±0.077, combined group: 0.850±0.069 vs untreated SHR: 0.428±0.038, P<0.01) expression and down-regulation of Smad6 (captopril: 0.720±0.104, combination: 0.631±0.041 versus untreated SHR: 0.959±0.099, P<0.01). Conclusion The effective components of Radix Paeoniae may improve renal fibrosis in hypertensive patients through the regulation of BMP/Smads pathway.