吴门芪藤汤对高脂饮食诱导的肥胖大鼠前交叉韧带横断和内侧半月板切除所致骨关节炎的影响

Effect of Wumen Qiteng decoction on anterior cruciate ligament transection and medial meniscectomy induced osteoarthritis in obese rats induced by high-fat diet

目的探讨吴门芪藤汤对肥胖膝骨关节炎(OA)大鼠膝软骨基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶组织抑制剂-1(TIMP-1)蛋白表达的影响。方法建立高脂饮食诱导的肥胖大鼠前交叉韧带横断和内侧半月板切除所致OA模型,以随机数字法将模型大鼠分为模型组、吴门芪藤汤组[24 g生药/(kg·d)],黄芪组[12 g生药/(kg·d)],黄芪甲苷组[60 mg/(kg·d)],每组10只。另选取10只同龄大鼠为空白组。吴门芪藤汤组、黄芪组、黄芪甲苷组大鼠给予相对应的药物灌胃,1次/d,连续处理4周,空白组与模型组给予等容积的生理盐水。实验结束后,生化法检测大鼠血清TG、TC、HDL-C、LDL-C水平;ELISA法测定SOD活性、MDA、TNF-α、IL-1β水平;HE染色观察大鼠膝关节软骨的病理变化;Western Blot法检测软骨组织中MMP-3和TIMP-1蛋白的表达情况。结果与空白组比较,模型组血清TG、TC、LDL-C、MDA、TNF-α、IL-1β水平以及软骨组织MMP-3和TIMP-1蛋白表达均显著升高,血清HDL-C水平和SOD活性显著降低,差异具有统计学意义(P<0.05);病理组织学检测结果显示模型组大鼠软骨组织存在损伤的病理变化。与模型组比较,吴门芪藤汤组、黄芪组、黄芪甲苷组的相关指标均有不同程度改善,且吴门芪藤汤的效能最为明显。结论吴门芪藤汤能够改善肥胖大鼠前交叉韧带横断和内侧半月板切除所致OA软骨损伤,调节血脂相关指标,抑制炎症反应、氧化反应,其对肥胖性膝OA的改善作用可能是通过降低膝关节软骨组织中MMP-3和TIMP-1蛋白表达而实现。

Objective To investigate the effects of Wumen Qiteng decoction on the expression of matrix metalloproteinase-3(MMP-3)and tissue inhibitor of metalloproteinases-1(TIMP-1)proteins in knee cartilage of obese knee osteoarthritis(OA)rats.Methods The OA model induced by anterior cruciate ligament transection and medial meniscectomy in obese rats induced by high-fat diet was established.The model rats were divided into model group,Wumen Qiteng decoction group[24 g crude drug/(kg·d)],Astragalus membranaceus group[12 g crude drug/(kg·d)]and Astragaloside Ⅳ group[60 mg/(kg·d)]by random number method,with 10 rats in each group.Another 10 rats of the same age were selected as blank group.The rats in the Wumen Qiteng decoction group,Astragalus membranaceus group and Astragaloside Ⅳ group were given the corresponding drugs by gavage,once a day,for 4 weeks,and the blank group and the model group were given the same volume of normal saline.After the experiment,the levels of serum TG,TC,HDL-C and LDL-C were detected by biochemical method;the levels of SOD activity,MDA,TNF-α and IL-1β were detected by ELISA method;the pathological changes of rats'knee cartilage was observed by HE staining;the expressions of MMP-3 and TIMP-1 proteins in cartilage tissue were detected by Western Blot.Results Compared with the blank group,the levels of serum TG,TC,LDL-C,MDA,TNF-α,IL-1β and the expressions of MMP-3,TIMP-1 proteins in cartilage tissue in the model group significantly increased,serum LDL-C level and SOD activity in the model group significantly decreased,and the differences were statistically significant(P<0.05);the histopathological examination showed that there were pathological changes of cartilage tissue damage in rats of the model group.Compared with the model group,relevant indexes could be improved in varying degrees in the Wumen Qiteng decoction group,the Astragalus membranaceus group and the Astragaloside Ⅳ group,and the efficacy of the Wumen Qiteng decoction was the most obvious.Conclusion The Wumen Qiteng decoction can improve OA cartilage injury caused by anterior cruciate ligament transection and medial meniscectomy in obese rats,regulates blood lipid related indexes,and inhibit inflammatory response and oxidation response.Its ameliorative effect on obese knee OA may be achieved by reducing the expression of MMP-3 and TIMP-1 proteins in knee cartilage.