三种不同浓度木瓜蛋白酶建立SD雌性大鼠膝骨关节炎模型的比较研究

Comparison Study on Knee Osteoarthritis Models in SD Female Rats Induced by Three Different Concentrations of Papain

目的对三种不同浓度木瓜蛋白酶所建立的SD雌性大鼠膝骨关节炎模型进行比较研究,以提供不同损伤程度的膝骨关节炎动物模型的建立方法。方法选取健康SD雌性大鼠72只,随机挑选18只为一组,各组在第1、3、5天均按0.1 m L/kg剂量左膝关节腔分别注射0.03 mol/L的L-半胱氨酸与2%、5%、10%(w/v)木瓜蛋白酶混合液,以及生理盐水,依次编为低浓度组、中浓度组、高浓度组和对照组。首次给药后第2、4、6周测量SD大鼠左膝关节宽度,各组随机处死6只大鼠对其进行解剖,观察膝关节滑膜及上下软骨表面,并进行大体及组织病理学评分。结果 SD雌性大鼠注射不同浓度木瓜蛋白酶2周后,出现不同程度的左膝关节宽度增大,左膝关节解剖后,可见滑膜厚度有所增加,软骨层损伤等病变,对照组与部分造模组的差异有统计学意义。结论 SD雌性大鼠按0.1m L/kg剂量膝关节腔注射2%、5%、10%木瓜蛋白酶和0.03 mol/L的L-半胱氨酸混合液,两周后可得到不同损伤程度的膝骨关节炎模型,在研究范围内,随着木瓜蛋白酶注射浓度的升高,所得膝骨关节炎模型的损伤程度加重,此造模方法操作简单、成功率高、周期短。

Objective To compare the knee osteoarthritis（ OA） models in SD female rats induced by three different concentrations of papain and provide methods for establishing different severities models of knee osteoarthritis. Methods Seventy two SD female rats were randomly divided into four groups of 18 each,and given injections into the three experimental groups＇ left knees on days 1,3 and 5 including intra-articular injections of 0. 03 mol / L L-cysteine and 2%（ low concentration group）,5%（ middle concentration group）,or 10%（ high concentration group）（ w / v） papain at the dose of 0. 1 ml / kg.The 0. 9% Na Cl（ w / v） with a dose of 0. 1 ml / kg were injected intra-articularly into the left knees of SD female rats in the control group. The SD female rats were sacrificed at 2,4,6 weeks respectively after the initiation of papain injection and these OA models were evaluated through recording the width of each left knee joint,performing the morphological observation and histological evaluation of articular cartilage and synovium. Results After the second week of the initiation of different concentrations of papain,the width of SD female rats＇ left knees increased by varying degrees,and the anatomy of left knee showed an increase in the thickness of the synovial membrane,cartilage damage and other diseases,none of these changes were found in the control group. In score results,the differences between the control group and part of the model groups were statistically significant. Conclusion Different severities of knee OA in SD female rats are established through intra-articular injections of 2% 5% or 10% papain and 0. 03 mol / L L-cysteine at the dose of 0. 1 ml / kg after the second week of the initiation,and the severities of knee osteoarthritis models are worse as papain injection concentration increases within the scope of the study. This modeling method is simple and has high successful rate and short cycle.