甲状旁腺激素（1-34）对骨质疏松相关性骨性关节炎的作用

发布时间：2018-04-22 19:23

本文选题：骨性关节炎 + 软骨下骨　；参考：《华北理工大学》2017年硕士论文

【摘要】：目的本次实验的目的旨在应用甲状旁腺激素(Parathyroid hormone,PTH)干预Sprague-Dawley(SD)大鼠双侧卵巢切除术(Ovariectomy,OVX)导致的骨质疏松相关的骨关节炎(Osteoarthritis,OA)模型中,研究PTH对关节软骨及软骨下骨的作用。方法18只6月龄SPF级SD大鼠随机分为3组每组6只,即:Sham组、OVX+NS组和OVX+PTH组,OVX+NS组和OVX+PTH组行双侧卵巢切除术。术后一周OVX+PTH组给予PTH10mg/kg/day皮下注射,每周五次,OVX+NS组给予等量生理盐水皮下注射。给药12周后处死动物,对膝关节行Micro-CT骨组织形态学测定,甲苯胺蓝染色和COL-II、MMP-13免疫组化染色。甲苯胺蓝染色切片行OARSI组织学评分;免疫组化阳性蛋白表达行IOD评分。应用SPSS17对各组数据进行统计学分析。结果1在OARSI组织学评分中OVX+NS组与OVX+PTH组比较,OVX+NS组与Sham组比较,总软骨退变宽度评分均无明显差异,未出现明显软骨损伤,也未出现明显基质和软骨浅层细胞损失,潮线连续性好,关节边缘未见明显骨赘形成。2 Micro-CT分析:OVX+NS组与Sham组比较,OVX+NS组BMD显著降低(P0.05),OVX+PTH组与OVX+NS组比较,OVX+PTH组BMD显著增加(P0.05)。Sham组与OVX+NS组比较,OVX+NS组骨体积分数(BV/TV)显著降低(P0.05);OVX+NS组与OVX+PTH组相比较,OVX+PTH组骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)均显著升高(P0.05)。3关节软骨免疫组化IOD评分显示:OVX+PTH组与OVX+NS组比较,OVX+PTH组Col-II阳性表达有增加趋势,但未见显著差异;OVX+NS组与Sham组比较,OVX+NS组Col-II阳性表达显著降低,有统计学意义差异(P0.05)。OVX+NS组分别与Sham组和OVX+PTH组比较,OVX+NS组MMP-13免疫组化染色阳性表达均显著增加(P0.05)。结论1.OVX加速大鼠软骨下骨和关节软骨退变,6月龄OVX大鼠是一种轻微的绝经后OA大鼠模型。2.PTH可改善OVX导致的软骨下骨骨量丢失与微结构,这可能有助于维持关节软骨的局部力学环境。3.PTH减缓关节软骨退变。
[Abstract]:Objective to investigate the effects of PTH on articular cartilage and subchondral bone in bilateral ovariectomy-induced osteoarthritis induced by bilateral ovariectomy (OVX) in rats with parathyroid hormone (PTH). Methods Eighteen 6-month-old SPF SD rats were randomly divided into 3 groups, 6 rats in each group, namely, the OVX PTH group, the OVX PTH group, the OVX NS group and the OVX PTH group. One week after operation, the OVX PTH group was subcutaneously injected with PTH10mg/kg/day, and the OVX NS group was given the same amount of normal saline subcutaneously five times a week. After 12 weeks of administration, the animals were killed. The bone morphology of Micro-CT, toluidine blue staining and COL-IIP MMP-13 immunohistochemical staining were performed on the knee joint. Toluidine blue staining section was stained with OARSI histological score, and immunohistochemical positive protein expression was evaluated with IOD score. The data of each group were analyzed statistically by SPSS17. Results (1) in OARSI histological score, there was no significant difference in total cartilage degeneration width between OVX NS group and OVX PTH group, and there was no obvious cartilage injury, and no obvious matrix and superficial cartilage cell loss in OVX NS group and Sham group. The continuity of the tidal line is good. 2 Micro-CT analysis of osteophyte formation at articular edge; BMD in OVX NS group was significantly lower than that in Sham group; BMD in OVX PTH group was significantly lower than that in OVX NS group; BMD in OVX PTH group was significantly higher than that in OVX NS group and the bone volume fraction in OVX NS group was significantly lower than that in OVX NS group. Compared with OVX PTH group, the bone volume fraction (BV / TVV) and trabecular thickness (Tb. Th) of OVX PTH group were significantly higher than that of OVX PTH group. The immunohistochemical IOD score of articular cartilage showed that the Col-II positive expression of OVX PTH group in the PTH group was increased compared with that in the OVX NS group. However, there was no significant difference between OVX NS group and Sham group. The positive expression of MMP-13 in OVX NS group was significantly lower than that in Sham group and OVX PTH group. There was a significant difference in Col-II expression between OVX NS group and Sham group and OVX PTH group. The expression of MMP-13 immunohistochemical staining in OVX NS group was significantly higher than that in Sham group and OVX PTH group. Conclusion 1.OVX accelerated subchondral bone and articular cartilage degeneration in 6-month-old OVX rats is a mild postmenopausal OA rat model. 2. PTH can improve the bone loss and microstructure of subchondral bone induced by OVX. This may help to maintain the local mechanical environment of articular cartilage. 3. PTH can slow the degeneration of articular cartilage.
【学位授予单位】：华北理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R580;R684.3

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