JAK2/STAT3信号通路介导姜黄素在骨性关节炎软骨细胞代谢中的影响

JAK2 / STAT3 signal pathway mediating curcumin in cartilage cell metabolism of osteoarthritis

目的 ：探讨酪氨酸蛋白激酶2/信号转导和转录激活子3（JAK2/STAT3）信号通路对软骨细胞代谢的影响以及线粒体抗氧化应激能力的改变,及JAK2/STAT3信号通路在此过程中的作用以及姜黄素对其影响。方法：选取雄性SPF级C57BL/6小鼠15只,体重10.05~15.00 g,平均12.80 g,随机分为对照组、OA组（Glasson法建立OA模型）及姜黄素＋OA组（在OA组处理的基础上,术后每日腹腔注射100 mg/kg姜黄素）,每组各5只。4周后用脱颈法处死3组小鼠取材,观察各组大体标本形态学变化及采用免疫组织化学法观察标本改变;采用Western blot蛋白印迹法检测各组p-JAK2、p-STAT3和Bax蛋白的表达,同时检测各组线粒体氧化应激指标琥珀酸脱氢酶（SDH）及细胞色素C氧化酶（COX）改变。结果：4周后,在软骨组织标本形态学方面,对照组软骨组织呈半透明状,无肿胀、充血,软骨细胞数量多,胞核呈椭圆形,染色质分布均匀;姜黄素＋OA组关节轻微肿胀,无充血,软骨细胞形态较规则,细胞数量略减少;OA组关节面粗糙,表面变薄、有轻度破损现象,细胞排列稍紊乱,视野下可见核消失,染色不均匀。与对照组相比,OA组和姜黄素＋OA组软骨细胞p-JAK2、p-STAT3蛋白表达降低（P〈0.05）、Bax蛋白表达升高（P〈0.05）,SDH和COX蛋白水平表达均降低（P〈0.05）;与OA组比较,姜黄素＋OA组软骨细胞p-JAK2、p-STAT3蛋白表达升高,Bax蛋白表达降低,SDH和COX蛋白水平表达均升高,差异有统计学意义（P〈0.05）。结论：JAK2/STAT3信号通路与骨性关节炎软骨退变的病理过程密切相关,姜黄素可激活JAK2/STAT3信号通路,增加软骨细胞线粒体抗氧化应激能力,明显缓解关节软骨的退变,降低OA进展水平。

Objective：To observe influence of JAK2 / STAT3 signal pathway mediating curcumin in cartilage cell metabolism of osteoarthritis and mitochondria oxidative stress resistance;also explore the role of JAK2 / STAT3 signal pathway and effect of curcumin in this process. Methods：Fifteen male SPF C57 BL / 6 rats rweighted from 10.05 to 15.00 g with an average of 12.80 g were collected and randomly divided into control group,OA group（modeled as OA by Glasson SS）,curcumin with OA group（100 mg / kg curcumin were performed intraperitoneal injection every day based on OA group）,5 rats in each group. Rats were taken off the neck after 4 weeks, morphologic change were observed,specimens changes were observed by histochemical methods;p-JAK2,p-STAT3 and Bax protein expression were detected by Western blot;At the same time,the changes of mitochondria oxidative stress index such as succinate dehydrogenase（SDH） and cytochrome C oxydase（COX） in each group were detected. Results：After 4 weeks,cartilage tissue showed translucent shape,no swelling and congestion,the number of cartilage cell increased,nuclei liked oval,chromatin arranged uniform in control group;in curcumin with OA group,joint showed slightly swelling without congestion,the formation of cartilage cell was regular,and number of cell decreased;while in OA group,the surface of joint was roughness with mild damage,cell arrangement was a bit disorder,nuclear was disappeared under vision and dyeing was uneven. Compared with control group,p-JAK2,p-STAT3 protein expression was decreased in OA and curcumin with OA group（P〈0.05）,Bax protein expression was increased（P〈0.05）,SDA and COX proteinexpression were reduced（P〈0.05）. Compared with OA group,p-JAK2,p-STAT3 protein expression was increased in curcumin with OA,Bax protein expression was decreased（P〈0.05）,SDA and COX protein expression were increased（P〈0.05）,and had statistical differences among three groups. Conclusion：JAK2 / STAT3 signal pathway is closely associated with pathology course of osteoarthritis,curcumin could stimulate JAK2 / STAT3 signal pathway and promote mitochondria oxidative stress. It could obviously relieve degeneration of articular cartilage and slow lower progress of OA.