补肾中药通过调控Notch1蛋白的表达治疗大鼠骨质疏松性骨折的作用研究

发布时间：2018-06-23 23:23

本文选题：骨质疏松骨折 + 补肾法　；参考：《中国骨质疏松杂志》2017年11期

【摘要】：目的探究补肾中药对大鼠骨质疏松骨折的治疗作用和机制。方法选取老年雌性大鼠60只,分为正常组、骨质疏松骨折模型组、高、中、低剂量补肾中药治疗组,各组均摘除卵巢,术后3个月形成骨质疏松模型。随后除正常组外,其余各组均建立股骨骨折模型。骨质疏松骨折模型建立后,每日给予正常组与模型组生理盐水进行灌胃,治疗组分别给予高、中、低剂量补肾中药灌胃12 w进行治疗。末次实验结束后麻醉大鼠,应用双能X射线检测大鼠股骨的骨密度。采取血清样品通过ELISA法测量碱性磷酸酶、骨钙素、TRAP破骨标志物等指标含量,对股骨样品进行病理学检查以及Western blot法检测Notch1蛋白的表达。结果病理组织学切片结果显示,高剂量治疗组在骨折端的成骨细胞数量较多,破骨细胞数量较少,提示补肾中药具有促进骨性愈合的效果。经补肾中药治疗后,高剂量治疗组的骨密度与模型组相比骨密度显著回升。研究发现,strACP经过补肾中药治疗后,治疗组中的碱性磷酸酶与血清抗酒石酸性磷酸酶的含量显著降低,骨钙素含量明显提升,上述指标在高剂量治疗组中与模型组相比差异均具有统计学意义(P0.01),呈明显的剂量依赖性。另外,Western blot法检测结果也显示,Notch1蛋白的表达在模型组中受到显著抑制(与正常组相比,P0.01),而补肾中药具有调节Notch1蛋白表达的作用,成明显剂量相关性,且高剂量治疗组的表达水平与正常组接近。结论补肾中药能够通过调节Notch1蛋白的表达来抑制血清中破骨标志物碱性磷酸酶和TRAP的水平,并提高骨钙素的含量来刺激成骨细胞生成、抑制破骨细胞分化,从而加速骨折的愈合,提高骨密度,对大鼠股骨骨质疏松骨折具有良好的治疗作用。
[Abstract]:Objective to explore the therapeutic effect and mechanism of kidney tonifying herbs on osteoporotic fracture in rats. Methods Sixty old female rats were divided into normal group, osteoporotic fracture model group, high, middle and low dose group treated with traditional Chinese medicine for tonifying the kidney. The ovariectomies were removed in each group, and the osteoporosis model was established 3 months after operation. Then the femoral fracture model was established in all groups except the normal group. After the model of osteoporosis fracture was established, normal group and model group were given normal saline daily, and the treatment group were given high, middle and low doses of tonifying kidney Chinese medicine for 12 weeks. Bone mineral density (BMD) of femur was measured by dual energy X-ray in anesthetized rats after the last experiment. The contents of alkaline phosphatase, osteocalcin trap and osteoclast markers in serum samples were measured by Elisa, and the expression of Notch1 protein in femur was detected by pathological examination and Western blot. Results the results of histopathological section showed that the number of osteoblasts and osteoclasts in the high dose treatment group was more and the number of osteoclasts was less. It suggested that Chinese medicine for tonifying the kidney had the effect of promoting bone healing. BMD in high dose group was significantly higher than that in model group after treatment with tonifying kidney Chinese medicine. It was found that the contents of alkaline phosphatase and serum antitartrate phosphatase in the treatment group were significantly decreased and the osteocalcin content was significantly increased after the treatment of strACP with traditional Chinese medicine for tonifying the kidney. The above indexes in the high dose treatment group were significantly different from the model group (P0.01) in a dose-dependent manner. In addition, the expression of Notch1 protein in the model group was significantly inhibited by Western blot assay (compared with the normal group, P0.01), while the Chinese medicine for tonifying the kidney could regulate the expression of Notch1 protein in a dose-dependent manner. The expression level of high dose treatment group was similar to that of normal group. Conclusion Chinese herbs for tonifying kidney can inhibit the level of alkaline phosphatase and trap in serum osteoclast by regulating the expression of Notch1 protein, and increase the content of osteocalcin to stimulate osteoblast formation and inhibit osteoclast differentiation. It can accelerate fracture healing, increase bone density, and have good therapeutic effect on osteoporotic fracture of femur in rats.
【作者单位】：广州中医药大学第一临床医学院;广州中医药大学第一附属医院;广州中医药大学中医骨伤科学国家重点学科实验室;
【基金】：广东省自然科学基金项目(2016A030313641) 广州市科技计划项目(201707010460) 广州中医药大学中医骨伤科学国家重点学科开放基金资助(YB12) 2016年国家级大学生创新创业训练计划项目(201610572262) 广东省科技厅项目(2016A020215137)
【分类号】：R285.5

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