白藜芦醇对去卵巢骨质疏松大鼠Wnt/β-Catenin通路的影响

目的: 研究白藜芦醇（RES）对卵巢摘除骨质疏松大鼠Wnt/β-Catenin信号通路的影响，探索RES对卵巢摘除的骨质疏松大鼠的保护作用及机制。方法: 选用60只健康雌性SPF级大鼠，随机分为假手术组（Sham组）12只、模型组（OVX组）48只，通过摘除大鼠双侧卵巢的方法，建立骨质疏松模型。12周后，测量骨密度（BMD），将造模成功的大鼠随机分为OVX组、白藜芦醇低（RES-L,5 mg·kg-1·d-1）、中（RES-M,15 mg·kg-1·d-1）、高（RES-H,45 mg·kg-1·d-1）剂量组，每组12只，灌胃给药，假手术组和模型组给予灌服等量的生理盐水，每天一次，连续12周。ELISA法检测血清雌激素（E2）、孕激素（P）和抗酒石酸酸性磷酸酶（TRAP）水平的变化；测量各组BMD；采用RT-PCR法检测β-Catenin、糖原合成酶激酶3β（GSK-3β）、低密度脂蛋白受体相关蛋白5（LRP5）及Runx2 mRNA的表达。结果: OVX组BMD较Sham组显著降低（P<0.01），表明造模成功。药物干预12周后，与Sham组相比，OVX组的BMD显著降低（P<0.01）；而RES各组的BMD显著升高；同OVX组相比，经RES干预后，BMD、β-Catenin mRNA、LRP5 mRNA及Runx2 mRNA等在RES诱导后的OVX组中表达显著增高（P<0.01）；GSK-3β mRNA表达显著减少（P<0.05）。结论: 白藜芦醇可显著提高去卵巢骨质疏松大鼠的BMD值，其机制与上调Wnt/β-Catenin信号通路相关。

Effect of resveratrol on the Wnt/β-Catenin pathway in ovariectomized osteoporosis rats

AIM: To study the effect of resveratrol (RES) on the expression of Wnt/β-Catenin signaling pathway in ovariectomized osteoporosis rats, and to investigate the protective effect and its possible mechanism. METHODS: Sixty female SPF rats were randomly divided into sham operation group (Sham, n=12) and ovariectomized group (OVX, n=48). Ovariectomy was performed to establish the ostoporotie model. The bone density (BMD) was detected after 12 weeks to assure the successful modeling. OVX group were thus randomly divided into OVX group, resveratrol low (RES-L, 5 mg·kg-1·d-1), resveratrol middle (RES-M, 15 mg·kg-1·d-1) and high dose group (RES-H, 45 mg·kg-1·d-1), with twelve rats in each group receiving gavage, while the sham operation group and model group were given normal saline of the same dose. Drug intervention was performed once a day and lasted for 12 weeks. Levels of serum progesterone (P) and estradiol (E2) and expression of tartrate-resistant acid phosphatase (TRAP) were detected by ELISA method; BMD was measured; Expression of β-Catenin, glycogen synthasc kinase-3β (GSK-3β), low-density lipoprotein receptor-related protein 5 (LRP5) and Runx2 mRNA was detected by RT- PCR method. RESULTS:The BMD of OVX group was significantly lower than that of the Sham group (P<0.05), which suggested successful modeling; after drug intervention for 12 weeks, BMD of the OVX group decreased significantly (P<0.05), while that of the RES groups increased significantly compared with Sham group; compared with the OVX group, the expression of BMD, β-Catenin, LRP5 and Runx2 mRNA in RES groups increased significantly (P<0.05); the expression of GSK-3β mRNA decreased significantly(P<0.05).CONCLUSION: Res can significantly improve the BMD of ovariectomized rats, and the mechanism is related with up-regulating the Wnt/β-Catenin signaling pathway.