雷奈酸锶对豚鼠继发性骨关节炎模型关节软骨及软骨下骨的保护作用

发布时间：2018-01-28 19:52

本文关键词： 骨性关节炎雷奈酸锶软骨下骨免疫组化 micro-CT　出处：《华北理工大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的本次实验的目的旨在研究早期应用雷奈酸锶(strontium ranelate,SR)干预对Dunkin-Hartley(DH)豚鼠内侧半月板切除(medial meniscectomy,MMT)导致的继发性骨关节炎(osteoarthritis,OA)模型中关节软骨及软骨下骨的作用。方法36只3月龄SPF级DH豚鼠随机分为3组每组12只,即:Sham组、MMT+NS组和MMT+SR组。MMT+NS组和MMT+SR组行右膝关节内侧半月板切除术,Sham组切开至皮下组织后缝合。术后一周MMT+SR组给予SR625mg/kg·d灌胃,MMT+NS组给予等量生理盐水灌胃,Sham组不作给药处理。给药12周后处死动物,每组取6只动物解剖右膝关节肉眼观察膝关节外观及滑膜、滑液并对关节进行OARSI大体评分,之后应用Micro-CT对右胫骨近端行骨密度及骨组织形态学测定;其余动物右膝关节脱钙12周,石蜡包埋切片,行甲苯胺蓝染色和COL-II、MMP-3、OPG及RANKL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IRS评分,并对各组数据进行统计学分析。结果MMT+NS组OARSI评分、Tb.Sp及MMP-3表达水平均显著高于Sham组(P0.05),BMD、BV/TV、Tb.Th及Col-II表达水平均显著低于Sham组(P0.05),Tb.N及OPG/RANKL与Sham组无显著差异;MMT+SR组BMD、BV/TV及Tb.Th均显著高于MMT+NS组(P0.05),Tb.Sp显著低于MMT+NS组(P0.05),OARSI评分、Tb.N及各因子表达水平与MMT+NS组均无显著差异。结论1 DH豚鼠MMT术后关节软骨及软骨下骨表现出与人类继发性OA相似的病理改变,因此是一种研究OA发病机制的可靠动物模型。2在DH豚鼠继发性OA模型中SR 625 mg/kg·d灌胃12周,显著减少软骨下骨骨量丢失,但对关节软骨退变未表现出显著影响。
[Abstract]:Objective to study the early application of strontium ranelate. The medial meniscectomy was removed from medial meniscus of Dunkin-Hartleyus. MMT-induced osteoarthritis of secondary osteoarthritis. Methods 36 3-month-old SPF DH guinea pigs were randomly divided into 3 groups (n = 12 in each group). MMT NS group and MMT SR group. MMT NS group and MMT SR group were treated with medial meniscal excision of right knee. One week after operation, the MMT SR group was given SR625mg/kg 路d intragastric perfusion and the NS group was given the same amount of normal saline. The animals in Sham group were killed after 12 weeks of administration. 6 animals in each group were dissected to observe the appearance and synovium of the right knee joint with naked eyes, and synovial fluid was used to evaluate the OARSI gross score of the joint. Bone mineral density (BMD) and bone histomorphology of proximal right tibia were measured by Micro-CT. The other animals were decalcified at right knee for 12 weeks, paraffin embedded sections, toluidine blue staining and COL-IIP MMP-3. OPG and RANKL immunohistochemical staining. Toluidine blue staining sections for OARSI histological score, immunohistochemical positive protein expression for IRS score. Results the expression of OARSI score Tb.Sp and MMP-3 in MMT NS group was significantly higher than that in Sham group (P 0.05). There was no significant difference in Tb.Th and Col-II expression levels between Sham group and Sham group. Both BMD V / TV and Tb.Th in MMT SR group were significantly higher than those in MMT NS group (P 0.05) and Tb.Sp was significantly lower than that in MMT NS group (P 0.05). OARSI score. There was no significant difference in the expression of Tb.N and other factors between the MMT NS group and the MMT NS group. Conclusion 1 the articular cartilage and subchondral bone of DH guinea pigs after MMT showed similar pathological changes as those of human secondary OA. Therefore, it is a reliable animal model to study the pathogenesis of OA. 2 in DH guinea pig secondary OA model, SR 625 mg/kg 路d gastric perfusion for 12 weeks, significantly reduce bone loss in subchondral bone. However, there was no significant effect on articular cartilage degeneration.
【学位授予单位】：华北理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R684.3

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