中国骨质疏松杂志

温肾健脾方通过HIF-1α信号通路防治骨质疏松症的作用机制

The mechanism of treating osteoporosis through HIF-1α signaling pathway by Wen Shen Jian Pi prescription

DOI：10.3969/j.issn.1006-7108.2025.04.001

英文关键词:osteoporosis Wen Shen Jian Pi Prescription HIF-1α H-type blood vessels intestinal bone axis

基金项目:国家自然科学基金青年项目（82104709）；2024年度辽宁省教育厅高校基本科研项目“储备项目”(LJ212410162021)

作者	单位
方佳琪1 钟妍苑2 孙鑫1* 付夜平1 李俊儒1	1.辽宁中医药大学中医学院,辽宁沈阳 110847 2.广州中医药大学惠州医院（惠州市中医医院）,广东惠州 516005

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中文摘要:

目的观察温肾健脾中药在防治骨质疏松症（osteoporosis，OP）过程中缺氧诱导因子-1α（hypoxia inducible factor-1α，HIF-1α）的改变，探索温肾健脾方对OP的防治机制。方法随机将30只雄性大鼠分为正常组、模型组、中药组，每组10只。模型组采用尾部悬吊+氢化可的松注射+番泻叶灌胃+饮食失节的方法构建脾肾阳虚型OP模型，中药组同时灌胃8周。双能X线检测大鼠股骨骨密度(BMD)，酶联免疫吸附法(ELISA)测定血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRACP)含量，免疫荧光检测骨组织中CD31、EMCN的含量，RT-PCR检测肾、骨、肠中CD31、EMCN、HIF-1α的mRNA含量变化，蛋白质印迹检测肾、骨、肠中HIF-1α的蛋白水平。结果与正常组相比，模型组BMD降低，ALP、TRACP升高，肾、骨及肠CD31及EMCN的mRNA表达降低，肾、骨组织HIF-1α的mRNA及蛋白表达升高，NOTCH1蛋白表达降低，肠组织HIF-1α的mRNA表达增加，但蛋白表达降低；与模型组相比，中药组BMD升高，ALP、TRACP的含量下降，但ALP的效果不明显，肾、骨组织CD31、EMCN蛋白表达升高， HIF-1α表达降低，NOTCH1蛋白表达增加，肠组织HIF-1α的mRNA表达降低，但蛋白表达升高。结论脾肾阳虚型OP动物模型构建成功，且温肾健脾方能够改善骨质疏松症，促进H型血管生成，调节OP大鼠肾、骨组织HIF-1α、NOTCH1表达，其机制可能与HIF-1α信号通路调节H型血管生成有关。

英文摘要:

Objective To study the mechanism of the effect of Wen-Shen-Jian-Pi (WSJP) Prescription on the prevention and treatment of osteoporosis (OP) by tracking the changes of hypoxia inducible factor-1α(HIF-1α). Methods Thirty male rats were randomly divided into normal group, model group and traditional Chinese medicine group, with 10 rats in each group.The rats in model group with hydrocortisone injection and senna leaf gavage were suspended by their tails and fed improper diets to construct the OP rat model. The Chinese medicine group was gavaged at the same time for 8 weeks. Bone mineral density (BMD) was detected by dual-energy X-ray. The serum alkaline phosphatase(ALP) and tartrate-resistant acid phosphatase(TRACP) were determined with enzyme-related immunosorbent assay(ELISA). Immunofluorescence to detect CD31 and EMCN in bone tissues, as well as PT-PCR to detect CD31, EMCN and HIF-1α mRNA in the kidney, bone, and intestinal tissues. Meanwhile, the expression levels of protein of HIF-1α in the kidney, bone, and intestinal tissues were checked by Western blot. Results Compared with the normal group, the BMD of rats in the model group decreased, the content of ALP and TRACP was increased , and the mRNA expression levels of CD31 and EMCN in kidney, bone, and intestinal tissues decreased. Furthermore, the model group rats exhibited increased HIF-1α mRNA and protein expression levels in kidney and bone tissue, increased HIF-1α mRNA expression levels in intestinal tissue, but decreased protein expression levels in intestinal tissue. Compared with the model group, the traditional Chinese medicine group showed an increase in BMD and a decrease in ALP and TRACP level in rats. However, the decreasing level of ALP was not significant. On the other hand, the expression levels of CD31 and EMCN proteins in kidney and bone tissues were found to be increased. Moreover, the traditional Chinese medicine group showed a decrease in HIF-1α expression levels in kidney and bone tissue. In intestinal tissue, the HIF-1α mRNA expression levels decreased, but the protein expression levels increased. Conclusion The animal model of spleen-kidney-yang deficiency osteoporosis was established successfully. Besides, WSJP Prescription is able to treat osteoporosis by boosting H-type angiogenesis, adjusting the expression levels of HIF-1α and NOTCH1 in the kidney and bone tissues. This mechanism may be closely related to the regulation of the H-type angiogenesis through HIF-1α pathway.

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