补肾中药对骨质疏松症大鼠下丘脑BMP-4、Smad6 mRNA及蛋白表达的影响

Effects of nourishing-kidney herbs on the mRNA and protein expression of BMP-4 and Smad6 in hypothalamus of rats with osteoporosis

目的探索肾虚骨质疏松症的病理机制,研究补肾中药对肾虚骨质疏松大鼠防治作用的机理。方法实验采用去双侧卵巢的方法,建立肾虚骨质疏松症模型。补肾中药复方(高、中、低)剂量对实验大鼠治疗12周,以骨疏康颗粒、盖天力牡蛎钙作为阳性对照药,并设正常对照组和模型空白组。用RT-PCR法、Western印迹法检测肾虚骨质疏松症大鼠下丘脑组织中BMP-4、Smad6 mRNA和蛋白表达。结果①与正常组比较,模型空白组大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达水平明显增强;Smad6 mRNA和蛋白表达水平明显降低。②与模型空白组比较,补肾中药组对模型大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达明显降低;而Smad6 mRNA和蛋白表达明显增强。结论肾虚骨质疏松症的病理机制为肾精不足,骨髓、脑髓失养,表现在下丘脑-垂体-靶腺轴的调控失常,包括下丘脑组织的细胞因子及其信号传导通路的异常。

Objective TO investigate the pathomechanism of kidney deficiency type osteoporosis, and research the mechanism of preventive and therapeutic effect of nourishing-kidney herbs on rats with kidney deficiency type osteoporosis. Methods Established the rat models with kidney deficiency type osteoporosis by ovariectomy in the experiments. Treated the experimental rats with the complex prescription of nourishing-kidney herbs （high, middle, low dosage） for 12 weeks, Gushukang granule group and Gaitianli oyster shell-calcium group as positive control group, also set normal control and blank model group. Detected the mRNA and protein expression of BMP- 4 and Smad6 in hypothalamus of rats with kidney deficiency type osteoporosis by using RT-PCR and Western Blotting methods. Results First, compared with the normal group, the mRNA and protein expression of BMP-4 in the hypothalamus tissue of blank model group rats increased evidently, and the mRNA and protein expression of Smad6 decreased evidently. Second, compared with the blank model group, the mRNA and protein expression of BMP-4 in the hypothalamus tissue of model rats decreased sharply in nourishing-kidney herbs group, and the mRNA and protein expression of Smad6 increased sharply. Conclusion Deficiency of kidney-essence resulting in the non-nourishing of marrow and brain as the pathomechanism of kidney deficiency type osteoporosis could be revealed, showed as the abnormal regulation of hypothalamus-appendix cerebri-target gland core, including the abnorrnity of eytokine and its signal conduction path in the hypothalamus tissue.