摘要
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.
出处
《中国骨伤》
CAS
2016年第12期1104-1109,共6页
China Journal of Orthopaedics and Traumatology
基金
国家自然科学基金资助项目(编号:81371983)
甘肃省科技支撑计划(编号:S04671)
甘肃省自然科学基金项目(编号:1606RJZA208)
甘肃省青年科技基金项目(编号:1606RJYA300)~~
关键词
骨关节炎
姜黄素
软骨细胞
代谢
Osteoarthritis
Curcumin
Chondrocytes
Metabolism