补肾通络方改善骨质疏松大鼠糖代谢的作用及机制

Mechanism of Bushen Tongluo Decoction improving Effect on Glucose Metabolism in Osteoporpsis Rats

目的：探讨补肾通络方对去卵巢骨质疏松大鼠脂肪、骨骼肌过氧化物酶体增殖物激活受体γ辅助激活因子1α（PGC-1α）和葡萄糖转运蛋白4（GLUT4）表达的干预效应及对糖代谢的作用机制。方法：将雌性大鼠随机分为假手术组和手术组,分别为22只和60只,全部进行卵巢切除造模。术后70 d从2组分别随机选出10只大鼠处死后取右侧股骨,采用双能X射线骨密度仪进行检测。确认造模成功后,假手术组剩12只,手术组剩48只,手术组大鼠随机分为4组,分别为模型组、补肾方组、通络方组、补肾通络方组,每组12只。各给药组分别给予补肾方（5.4 g·kg^（-1））,通络方（0.9 g·kg^（-1））,补肾通络方（6.3 g·kg^（-1））进行灌胃,连续70 d。实验结束后,检测血糖和骨密度。通过实时荧光定量聚合酶链式反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测脂肪、骨骼肌PGC-1α和GLUT4 mRNA和蛋白的表达。结果：与假手术组比较,模型组血糖略升高,骨密度显著下降（P〈0.01）,脂肪、骨骼肌PGC-1α和GLUT4表达显著下降（P〈0.01）。与模型组比较,补肾通络方组大鼠血糖明显下降,脂肪、骨骼肌PGC-1α和GLUT4 mRNA和蛋白表达均明显增加（P〈0.05,P〈0.01）。结论：补肾通络方通过促进脂肪及骨骼肌PGC-1α表达,增加GLUT4表达,提高糖代谢水平。

Objective： To explore the effect and mechanism of Bushen Tongluo decoction（ BSTL） on the glucose metabolism of osteoporosis of ovariectomized rat model based on the expressions of peroxisome proliferator activated receptor γ coactivator-1α（ PGC-1α） and glucose transporter 4（ GLUT4） in fat and muscle. Method：Female rats were randomly divided into the sham operation group（ n = 22） and the operation group（ n = 60）; and all of them underwent ovary resection for modeling. 70 days after surgery,10 rats from the two groups were randomly selected and put to death,and their right femurs were collected. The dual-energy X-ray bone density instrument was used to test whether the models were successful or not. After the successful modeling,the shamoperated group still had 12 rats,and the operation group still had 48 rats. The operation group was divided into model group,kidney-tonifying drugs group（ 5. 4 g·kg^（-1））,deoppilant group（ 0. 9 g·kg^（-1））,and BSTL group（ 6. 3 g·kg^（-1））,with 12 rats in each group. The osteoporosis rat model was respectively given kidney-tonifying drugs,deoppilant,and BSTL by gavage for 70 days. Blood glucose and bone mineral density（ BMD） of the rat model were tested after the experiment. The mRNA and protein expression levels of PGC-1α and GLUT4 were detected in adipose tissue and skeletal muscle by Real-time PCR and Western blot. Result： Compared with the sham-operated group,the blood glucose of model groups was raised. The expression levels of BMD,PGC-1α and GLUT4 in adipose tissue and skeletal muscle were obviously declined（ P〈0. 01）. Compare with model groups,the blood glucose level of BSTL was decreased（ P〈0. 01）,and the expression levels of PGC-1α and GLUT4 were increased remarkably both in adipose tissue and skeletal muscle（ P〈0. 05,P〈0. 01）. Conclusion： BSTL increases the expression of GLUT4 and the level of glucose metabolism by promoting the expression of PGC-1α in adipose tissue and skeletal muscle.