基于JAK/STAT3信号通路探讨右归丸对骨关节炎模型大鼠软骨细胞凋亡的影响

Effect of Yougui Pill on Chondrocyte Apoptosis in Osteoarthritis Model Rats Based on JAK/-STAT3 Signal Pathway

目的:探讨右归丸对骨关节炎(osteoarthritis,OA)模型大鼠软骨细胞凋亡的影响及作用机制。方法:48只SD大鼠随机分为假手术组12只和造模组36只,造模组采用改良Hulth法建立膝关节OA模型,假手术组接受假手术。将造模成功的大鼠分为模型组、右归丸组及塞来昔布组各11只,模型组、假手术组给予0.9%氯化钠溶液,右归丸组给予2 g/mL右归丸溶液,塞来昔布组给予0.4 mg/mL塞来昔布悬液灌胃,8周后检测并比较各组大鼠软骨Mankin评分、软骨细胞凋亡指数(apoptosis index,AI)以及软骨组织Janus激酶(janus kinase,JAK)2、信号传导和转录激活因子(signal transducer and activator of transcription,STAT)3、B淋巴细胞瘤(B-lymphoma,Bcl)-2、Bcl-2关联XL蛋白(Bcl-2 associated X protein,Bax-XL)蛋白表达。结果:与假手术组比较,模型组大鼠软骨Mankin评分升高,软骨AI升高,软骨JAK2、STAT3、Bcl-2、Bcl-XL表达降低,差异有统计学意义(P<0.05);与模型组比较,右归丸组及塞来昔布组大鼠软骨Mankin评分降低,软骨AI降低,软骨JAK2、STAT3、Bcl-2、Bcl-XL表达升高,差异有统计学意义(P<0.05);右归丸组上述指标与塞来昔布组比较差异无统计学意义(P>0.05)。结论:右归丸能有效减轻OA大鼠软骨组织损伤,减少软骨细胞凋亡,其作用可能与激活JAK/STAT3信号通路、上调抗凋亡蛋白Bcl-2、Bcl-XL表达有关。

Objective:To investigate the effect and mechanism of Yougui pill on chondrocyte apoptosis in osteoarthritis(OA)model rats.Methods:48 SD rats were randomly divided into sham operation group with 12 rats and model group with 36 rats.The knee OA model was established by modified Hulth method,and the sham operation group received sham operation.The successfully modeled rats were divided into model group(n=11),Yougui pill group(n=11)and celecoxib group(n=11).The model group and sham operation group were given 0.9%sodium chloride solution,Yougui pill group was given 2 g/mL Yougui pill solution,celecoxib group was given 0.4 mg/mL celecoxib suspension.After 8 weeks,the cartilage Mankin score,chondrocyte apoptosis index(AI),and the expression levels of JAK2,STAT3,Bcl-2 and Bax-XL in cartilage were detected and compared.Results:Compared with the sham operation group,the Mankin score of cartilage was higher,the AI of cartilage was higher,and the expression levels of JAK2,STAT3,Bcl-2 and Bcl XL in cartilage were lower in model group,all the differences were statistically significant(P<0.05).Compared with the model group,the Mankin score of cartilage was lower,the AI of cartilage was lower,and the expression levels of JAK2,STAT3,Bcl-2 and Bcl XL in cartilage were higher in Yougui pill group and celecoxib group,all the differences were statistically significant(P<0.05).There was no significant difference in the above indexes between Yougui pill group and celecoxib group(P>0.05).Conclusion:Yougui pill can effectively reduce cartilage injury and chondrocyte apoptosis in OA rats.Its effect may be related to activating JAK/STAT3 signal pathway and up-regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL.