目的:研究左归丸对去卵巢骨质疏松大鼠的治疗作用及其机制。方法:SD雌性大鼠分为正常组,假手术组,模型组,左归丸高、中、低剂量组,及尼尔雌醇组,采用去卵巢的方法建立绝经后骨质疏松症模型,术后21 d开始给药:正常组,假手术组ig生理盐水;左归丸高、中、低剂量组分别ig 6.4,3.2,1.6 g·kg-1,1次/d;尼尔雌醇组ig 0.021 g·kg-1,1次/周,连续60d。取大鼠左后肢股骨远端1/3做病理切片,光镜下观察骨组织形态学变化,测定骨小梁面积百分比(Tb.Ar);采用双能X射线骨密度仪测定右后肢离体股骨近端1/3及股骨整体的骨密度(BMD);采用RT-PCR法检测大鼠肾髓质的转化生长因子-β1(TGF-β1)/Smad4 mRNA表达。结果:与模型组比较,左归丸高、中剂量组骨小梁面积百分率(Tb.Ar)显著升高(P〈0.05),左归丸高、中剂量组的股骨的骨密度显著升高(P〈0.05);各组肾脏组织病理形态学未见明显病理变化;与正常组相比,模型空白组TGF-β1,Smad4 mRNA水平过高表达(P〈0.05);与模型组相比,各给药组肾组织中TGF-β1,Smad4 mRNA表达均显著下调(P〈0.05),且左归丸各剂量组的下调力度均强于尼尔雌醇组,但以左归丸低剂量组下调最为显著。结论:左归丸能有效防治绝经后骨质疏松症,其作用机制之一可能与其干预肾组织中TGF-β1/Smad4的信号转导通路有关。
Objective: To study effect and mechanism of Zuogui Wan in ovariectomized osteoporosis rats. Method: SD female rats were divided into 7 groups : normal, Sham operation (Sham) , ovariectomized (OVX) , Zuogui Wan high- [ZG (H) ], Zuogui Wan middle-dose [ ZG (M) ], Zuogui Wan low-dose [ ZG (L) ] and nilestriol (N). The rat overiectomy-induced osteoporosis model was adopted, 21 days later, normal, Sham and OVX rats were ig given with dwas? tilled water. ZG (H, M, L) rats groups were ig given with Zuogui Wan at dosage of 6.4, 3.2, 1.6 g·kg-1 , once per day. N rats were ig given with 0. 021 g.kg-1 , once per week. Sixty days later, the left hind distal femur at the 1/3 side was taken to test the pathological section for determining the percentage of trabecular separation (Th · Ar). We determined the bone mineral density (BMD) of right hind proximate femur at the 1/3 and used the method of RT-PCR to test the expression of TGF-β1Smad4 mRNA in kidney medulla. Result: Compared with OVX, ZG (H) and ZG (M) increased Th. Ar and (P〈0.05). No pathological change in kidney tissues was found. Compared with normal group, the expression of TGF-β1/Smad4 mRNA in OVX rats increased (P 〈 0.05). Compared with OVX, the expression of TGF-β1Smad4 mRNA in Zuogui Wan treated groups was down-regulated (P 〈 0.05) , which was more significant in the total groups of Zuogui Wanl than that in nilestriol group, and low dosage of Zuogui Wan showed a most obvious down-regulation. Conclusion: Zuogui Wan can prevent and treat postmenopausal osteoporosis (PMOP) effectively. One of the mechanisms may he related to its interfering the TGF-β1/Smad4 signaling of the kidney tissue.