锌对SD大鼠膝骨关节炎早中期关节软骨的作用及对MMP-13表达的影响

摘要

Objective To study the effect of different doses of zinc on articular cartilage of Sprague-Dawley(SD) rat with osteoarthritis in early,middle phases and the expression of matrix metalloproteinase-13(MMP-13). Mehtods 64 SD rats were randomly diveded into four groups after had been an Modified Hulth modelling surgery on their knee joints,as follow:control group,low-dose zinc group,middle-dose zinc group and high-dose zinc group. The control group were treated with the normal sa-line at the same dose,and the cartilage sections were stained with hematoxylin-eosin(HE) and observed by light microscope, Mankin's score system was applied to analyze the degree of cartilage damage. The expression of MMP-13 in cartilage were detected using immunohistochemistry method. Positive expression was quantified by IOD score. Results At 4,8 weeks postoperatively, the degree of cartilage injury were more worse in the operation sides compared with the uninjured sides in control group,and there was a significant difference of Mankin scores between the two sides(P<0. 05). At 4 weeks postoperatively,there were no signifi-cant difference between the groups except the uninjured sides of control group. At 8 weeks postoperatively,Mankin scores was higher and the levels of MMP-13 expression was markedly lower in high-dose zinc group than that in control group(P<0.05).Conclusions OA model was established successfully. Early interventiobn with high-dose zinc for 8 weeks could protect the carti-lage in SD rats models of OA,and inhibited the expression of MMP-13 in cartilage tissue.%目的探讨不同剂量的锌对SD大鼠膝骨关节炎早中期软骨的作用及对MMP-13表达的影响。方法64只SD大鼠均行改良Hult法复制骨关节炎( OA)模型,随机分为对照组、低锌组、中锌组和高锌组,于术后第2天开始每天分别灌胃给予生理盐水、锌5 mg/kg、10 mg/kg、20 mg/kg,用药干预直到实验处死。分别于术后4周、8周光镜下对HE染色软骨组织标本行组织形态学观察及行Mankin评分比较,术后8周对软骨组织MMP-13免疫组化染色切片的灰度值行半定量分析。结果术后4周与8周,对照组术侧的软骨损伤明显比对照组健侧严重,Mankin评分比较差异有显著性(P<0.05)；术后4周,低锌组术侧、中锌组术侧和高锌组术侧软骨损伤与对照组术侧比较无明显差异,均为轻度软骨损伤,Mankin评分比较无统计学意义；术后8周,高锌组术侧的软骨损伤轻于对照组术侧,Mankin评分比较差异有显著性(P<0.05),MMP-13免疫组化染色切片的灰度值比较差异有显著性(P<0.05),其它各组在软骨损伤及MMP-13灰度值比较均无统计学意义。结论 SD大鼠膝骨关节炎造模成功；高剂量锌(每天20 mg/kg)给予8周对SD大鼠OA软骨具有保护作用,且能减少软骨组织MMP-13的表达。