葛根芩连汤治疗糖尿病骨质疏松大鼠的效果及机制

目的:研究葛根芩连汤治疗糖尿病性骨质疏松大鼠的效果及机制。方法:雌性SD大鼠60只,随机均分为3组。对照组20只无处理,余40只腹腔注射链脲佐菌素35 mg/kg,建立大鼠糖尿病模型。葛根芩连汤组:按生药量10 g/kg葛根芩连汤灌胃,模型组同法以0.9%NaCl灌胃,持续灌胃12周。行大鼠空腹胰岛素水平(Fins)、空腹血糖(FBG)、胰岛素敏感指数(ISI)及素抵抗指数(HOMA-IR)检测。RT-PCR、Western Blot检测椎体BMP-2/Smad表达变化,进一步行骨密度、骨钙含量及生物力学性能测定及HE染色。结果:模型组素HOMA-IR,FBG水平较对照组均升高,Fins及ISI降低(P<0.05)。葛根芩连汤组大鼠HOMA-IR,FBG水平与模型组比较降低,Fins及ISI均升高(P<0.05)。模型组大鼠椎体BMP-2、Smad1、Smad4基因和蛋白的表达较对照组降低(P<0.05)。葛根芩连汤组大鼠椎体BMP-2、Smad1、Smad4基因和蛋白较模型组升高(P<0.05)。模型组大鼠骨密度、骨钙含量、极限载荷、极限应力和弹性模量较对照组降低(P<0.05);葛根芩连汤组大鼠骨密度、骨钙含量、极限载荷、极限应力和弹性模量与模型组比较升高(P<0.05),HE染色示葛根芩连汤治疗后大鼠骨质疏松减轻。结论:葛根芩连汤在降低DOP大鼠血糖水平,减轻胰岛素抵抗,通过调高BMP-2/Smad通路发挥治疗大鼠DOP的作用。

Effect and Mechanism of Gegen Qinlian Decoction for the Treatment of Diabetic Osteoporosis Rats

To study the efficacy and mechanism of Gegen Qinlian Decoction(GQD)in the treatment of diabetic osteoporosis rats. Methods:A total of 60 female SD rats were randomly divided into 3 groups. The control group did not receive any treatment, and the remaining 40 were intraperitoneally injected with streptozotocin 35 mg/kg once to establish a rat model of diabetes. GQD group:According to the crude drug amount 10 g/kg, GQD was intragastrically administered to the rats. The model group was intragastrically administered with 0.9% NaCl for 12 weeks, and the rats, fasting insulin level(Fins), fasting blood glucose(FBG),insulin sensitivity index(ISI)and hormone resistance index(HOMA-IR)were detected. RT-PCR and Western Blot were used to detect the expression of BMP-2/Smad pathway in vertebral body, and the bone mineral density, bone calcium content, biomechanical properties and HE staining were further determined. Results:Compared with the control group, the HOMA-IR, the FBG level in rats of model group increased, and the Fins and ISI decreased(P<0.05).Compared with the model group, the HOMA-IR, the FBG level decreased, and the Fins and ISI were increased in the GQD group(P<0.05).Compared with the control group, the expression of BMP-2,Smad1,Smad4 gene and protein expression in the vertebral body of the model group was significantly lower(P<0.05).Compared with the model group, the expression of BMP-2,Smad1,Smad4 gene and protein expression in the vertebral body of the GQD group were significantly increased(P<0.05).Compared with the control group, the bone mineral density, bone calcium content, ultimate load, ultimate stress and elastic modulus of the model group were significantly lower(P<0.05).Compared with the model group, the bone mineral density, bone calcium content, ultimate load, ultimate stress and elastic modulus of the GQD group were significantly increased(P<0.05),HE staining showed that osteoporosis was alleviated in rats after treatment with Gegen Qinlian decoction. Conclusion:GQD can reduce the blood glucose level of diabetic osteoporosis rats and alleviate insulin resistance, and may play a role in the treatment of diabetic osteoporosis by increasing the BMP-2/Smad pathway.