探讨不同浓度碘乙酸钠对家兔早期膝关节骨性关节炎模型的诱导及病理改变
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摘要
目的探讨不同浓度碘乙酸钠对家兔早期膝骨性关节炎(osteoarthritis, OA)模型的诱导及病理改变,确定建立OA模型的最小有效药物浓度。方法将36只新西兰大白兔随机分为正常(A)组、模型(B～F)组,共6组,每组6只。A组左膝关节腔注射0.2 mL无菌生理盐水;B～E组左膝关节腔按照2.5、5、7.5、10 mg/kg剂量各注射0.2 mL的碘乙酸钠溶液,F组注射剂量与E组相同,同时以30 min/d分2次驱赶运动为干预因素。建模14 d后,采用HE染色及骨性关节炎组织病理学评分(Mankin评分)观察各组软骨的病理改变。结果 Mankin评分与A组相比,B、C组差异无统计学意义(P>0.05),D、E、F组差异有统计学意义(P<0.05);与E组比较,F组差异无统计学意义(P>0.05)。结论模型D组药物浓度7.5 mg/kg为建立OA模型的最小有效药物剂量,且模型建立方法操作简单、创伤小,能够保证膝关节稳定性及实验动物的成活率。
Objective To investigate the induction of early knee osteoarthritis(OA) model in rabbits with different concentrations of sodium iodoacetate and its pathological changes, and to identify the minimum effective drug concentration for establishing an OA model. Methods Thirty-six New Zealand white rabbits were randomly divided into one normal group(group A)and five model groups(groups B-F), with 6 rabbits in each group. Group A was injected with 0.2 ml sterile saline into the left knee joint cavity. Groups B-E were injected with 0.2 ml sodium iodoacetate solution into the left knee joint cavity at doses of 2.5, 5, 7.5,and 10 mg/kg, respectively. Group F did driving movement(30 min/d, twice daily) as the intervention factor in addition to the treatment for group E. The pathological changes of cartilage in each group were evaluated by HE staining and the histopathological score of OA(Mankin score). Results There were no significant differences in Mankin score between group A and groups B and C(P>0.05), but there were significant differences in Mankin score between group A and groups D, E, and F(P<0.05). There was no significant difference in Mankin score between group F and group E(P >0.05). Conclusion The drug concentration(10 mg/kg)in group D was the minimum effective dose for establishing OA model. The method of establishing OA model is simple and minimally invasive, which can ensure the stability of knee joint and the survival rate of experimental animals.
Objective To investigate the induction of early knee osteoarthritis(OA) model in rabbits with different concentrations of sodium iodoacetate and its pathological changes, and to identify the minimum effective drug concentration for establishing an OA model. Methods Thirty-six New Zealand white rabbits were randomly divided into one normal group(group A)and five model groups(groups B-F), with 6 rabbits in each group. Group A was injected with 0.2 ml sterile saline into the left knee joint cavity. Groups B-E were injected with 0.2 ml sodium iodoacetate solution into the left knee joint cavity at doses of 2.5, 5, 7.5,and 10 mg/kg, respectively. Group F did driving movement(30 min/d, twice daily) as the intervention factor in addition to the treatment for group E. The pathological changes of cartilage in each group were evaluated by HE staining and the histopathological score of OA(Mankin score). Results There were no significant differences in Mankin score between group A and groups B and C(P>0.05), but there were significant differences in Mankin score between group A and groups D, E, and F(P<0.05). There was no significant difference in Mankin score between group F and group E(P >0.05). Conclusion The drug concentration(10 mg/kg)in group D was the minimum effective dose for establishing OA model. The method of establishing OA model is simple and minimally invasive, which can ensure the stability of knee joint and the survival rate of experimental animals.
引文
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[3]宋寒冰,赵峰,葛圆圆,等.膝关节骨性关节炎动物模型建立的研究现状[J].中国医药导报,2017,14(30):46-49.
[4]柯晖.怀牛膝对兔骨性关节炎软骨组织影响的实验研究[D].武汉:湖北中医药大学,2012.
[5]方锐,艾力江·阿斯拉,卢勇,等.兔骨性关节炎模型构建及早中晚期的特点[J].中国组织工程研究与临床康复,2010,14(7):1218-1222.
[6]孙鲁宁,赵燕华,黄桂成,等.木瓜蛋白酶诱导膝关节骨关节炎模型兔滑膜病理变化与药物注射时间的关系[J].中国组织工程研究与临床康复,2011,15(50):9311-9313.
[7]葛广勇,赵建宁,刘刚.膝骨性关节炎模型的分期特征[J].中国组织工程研究,2006,10(4):47-49.
[8]杨瑞甫,胡蕴玉,吴银松,等.兔骨关节炎两种动物模型的比较[J].中国矫形外科杂志,2006,14(19):1497-1499.
[9]侯婷婷,王岩峰.关节腔内注射医用臭氧对兔膝骨性关节炎模型基质金属蛋白酶-9表达的影响[J].解剖科学进展,2017(1):76-79.
[10]曾俊华,马笃军,彭力平,等.实验兔膝骨关节炎模型的建立及鉴定[J].中国临床研究,2016,29(5):679-682.
[11]李文雄,孙赫,沈玮,等.SD大鼠骨关节炎造模方法的筛选及优化探究[J].畜牧与兽医,2014,46(10):70-73.
[12]陈志达,林瀚洋,余志毅,等.膝骨关节炎动物模型研究进展[J].风湿病与关节炎,2016,5(1):67-70.