川芎嗪对膝骨性关节炎大鼠软骨VEGF表达的影响

Effect of ligustrazine on the expression of VEGF in the cartilage in rats with knee osteoarthritis

目的观察川芎嗪治疗膝骨关节炎大鼠(KOA)模型关节软骨中VEGF蛋白表达的变化,并探讨川芎嗪治疗KOA的作用机制。方法制作大鼠膝关节炎模型,将建模成功的大鼠纳入模型对照组,常规饲养,川芎嗪高剂量组、川芎嗪低剂量组、阳性对照组分别行川芎嗪和塞来昔布灌胃干预,正常组和模型组行等量生理盐水,予以干预6周,实验结束后,分别行各组大鼠HE切片软骨Mankin评分、Western Blot检测软骨组织VEGF表达的变化。结果软骨Mankin评分中,川芎嗪各剂量组和阳性对照组均高于正常组、且均低于模型组(P<0.05),而阳性对照组评分低于川芎嗪低剂量组,但高于川芎嗪高剂量组(P<0.05)。正常组、川芎嗪各剂量组及阳性对照组中软骨VEGF相对表达量均低于模型组,差异有统计学意义(P<0.05);与阳性对照组相比,川芎嗪高剂量组VEGF表达量明显低于阳性对照组(P<0.05)、而川芎嗪低剂量组其表达则高于阳性对照组。结论川芎嗪对可能通过下调早期KOA大鼠VEGF的表达,抑制早期软骨血管新生而减轻炎症,这可能是在某种程度上减轻关节软骨退变、修复软骨损伤的作用机制之一。

Objective To observe the changes of the expression of bone morphologic VEGF protein in the joint cartilage of rat knee osteoarthritis（KOA） model treated with ligustrazine,and to investigate the mechanism of ligustrazine in the treatment of KOA. Methods Rat knee arthritis model was established. Rats with successful modeling were included in the model control group,with conventional breeding. Rats in ligustrazine high-dose group,ligustrazine low-dose group,and positive control group received ligustrazine and celecoxib lavage intervention,respectively. Rats in normal group and model group received same amount of normal saline for 6 weeks. At the end of the experiment,HE slices from rats of each group were used for cartilage Mankin score.Western blotting was used to test the changes of VEGF expression in the cartilage tissue. Results The cartilage Mankin scores in each ligustrazine dose group and positive control group were higher than in the blank group,but were lower than in the model group（P 〈 0. 05）. The scores in positive control group were lower than in ligustrazine low-dose group,but higher than in ligustrazine high-dose group（P 〈 0. 05）. The relative expressions of cartilage VEGF in the normal group,each ligustrazine dose group,and the positive control group were lower than in the model group,and the differences were statistically significant（P 〈 0. 05）. The expression of cartilage VEGF in the high-dose ligustrazine group was significantly lower than that in the positive control group（P 〈0. 05）,but the expression in low-dose group was higher than that in the positive control group. Conclusion Ligustrazine inhibitsearly angiogenesis of cartilage to reduce inflammation by down-regulation of VEGF expression in KOA rats,which to some extent may be one of the mechanisms of reducing joint cartilage degeneration and repairing cartilage damage.