目的:依据中医学"肾藏精生髓主骨"、骨的生长发育与肾精-脑髓-骨髓密切相关的藏象理论,研究肾虚骨质疏松症大鼠的相关病理机制以及补肾益髓中药调控作用机制.方法:采用去卵巢造模方法建立肾虚骨质疏松症大鼠模型,随机分为正常组、假手术组、模型空白组、补肾益髓中药低剂量组、补肾益髓中药高剂量组、补脾中药对照组、盖天力钙片对照组、骨疏康颗粒对照组;给予补肾益髓中药干预12w;以双能X线骨密度分析仪进行骨密度(BMD)检测,以RT-PCR法检测大鼠股骨、肾、下丘脑组织TGF-β1、TIEG1mRNA的表达,以Western Blot法检测股骨、肾、下丘脑组织TGF-β1、TIEG1蛋白表达.结果:与正常对照组比较,模型空白组骨、肾组织TGF-β1、TIEG1mRNA及蛋白表达水平明显降低(P＜0.01),而下丘脑组织明显升高(P＜0.01).用药12w后,与模型空白组比较,补肾益髓中药高剂量组可明显提高股骨头骨密度,明显优于补脾组中药(P＜0.01).补肾益髓高、低剂量组、盖天力组、骨疏康组可明显上调骨、肾组织TGF-β1 mRNA、蛋白以及TIEG1mRNA及蛋白表达水平(P＜0.01;P＜0.05);补肾益髓高、低剂量组、补脾组、盖天力组、骨疏康组均可明显下调下丘脑组织TGF-β1 mRNA、蛋白以及TIEG1mRNA及蛋白表达的表达水平(P＜0.01,P＜0.05).结论:肾虚骨质疏松症病理机制之一在于TGF-β1与TIEG1mRNA及蛋白表达异常,并可能存在下丘脑-肾-骨的反馈调节机制,揭示骨的生长发育与肾精-脑髓-骨髓密切相关的部分生物学依据;补肾益髓中药可以有效地防治该病症,对下丘脑-肾-骨反馈机制具有明显的调控作用,从而阐明中医学"肾藏精生髓主骨"藏象理论对临床实践的指导意义.

This study investigated the pathological expressions of transforming growth Factor β1（TGF-β1） and TGF-β-inducible early gene （TIEG1） on the mRNA and protein in the osteoporosis rats induced by ovarian removal, and determined the intervention of kidney-tonifying Chinese herbs to reveal the relative mechanisms of pathology and regulation by kidney-tonifying Chinese herbs. Experimental rat models were set up by removing ovaries, and randomly divided into eight groups: the normal, sham-operated, model control, low dose kidney-tonifying Chinese herbs, high dose kidney-tonifying Chinese herbs, spleen Chinese herbs control, Gaitianli calcium tablet control, and Gushukang particle control group. The medication of kidney-tonifying Chinese herbs lasted 12 weeks. Bone mineral density (BMD) was measured by dual energy X-ray absorbinmetry (DEXA). The expression of TGF-β1, TIEG1 mRNA and protein in the bone, kidneys and hypothalamus was measured with RT-PCR and Western blotting. Compared with the normal group, the model control group had the significantly decreased expression levels of TGF-β1，TIEG1 mRNA and protein in rat the bone and kidneys (P <0.01), and the significantly increased hypothalamus expression (P <0.01). 12 weeks after the medication, femoral bone mineral density in the high dosage kidney-tonifying Chinese herbs group was significantly increased compared with the model control group, and it was much higher than in the spleen Chinese herbs group（P <0.01）. The expressions of TGF-β1，TIEG1 mRNA and protein in rat bone and kidneys of the high and low dose kidney-tonifying Chinese herbs groups, Gaitianli calcium tablet control group, and Gushukang particle control group were significantly increased （P <0.01, P <0.05）, and that in the hypothalamus of each treated group was significantly decreased (P <0.01, P <0.05). In conclusion, one of the main pathological mechanisms in osteoporosis induced by ovarian removal is suggested to be the abnormal expression of TGF-β1, TIEG1mRNA and protein, possibly involving the feedback regulation mechanism of the hypothalamus?蛳kidney?蛳bone. The kidney?蛳tonifying Chinese herbs may control the disease by regulating the hypothalamus?蛳kidney?蛳bone feedback mechanism.

国家科学技术部等14部委和广东省人民政府共同主办的“2009’传统医药国际科技大会暨博览会”第三分会——“传统医药基础理论研究”论文，该论文为大会学术委员会评选的优秀论文；国家自然科学基金面上项目（30672570）：从UPP-Smad 蛋白信号网路调节机制对肾虚骨质疏松症证候病机研究，负责人：郑洪新。