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
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作者Author单位AddressE-Mail
李旭升 LI Xu-sheng 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
陈慧 CHEN Hui 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
甄平 ZHEN Ping 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
李慎松 LI Shen-song 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
周胜虎 ZHOU Sheng-hu 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
田琦 TIAN Qi 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China  
石杰 SHI Jie 甘肃省中医药大学, 甘肃 兰州 730000  
何晓乐 HE Xiao-le 第四军医大学西京医院老年病科, 陕西 西安 710032  
刘军 LIU Ju 兰州军区总医院全军骨科中心关节外科, 甘肃 兰州 730050 Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, Gansu, China tutuhehtt@126.com 
期刊信息:《中国骨伤》2016年,第29卷,第12期,第1104-1109页
DOI:10.3969/j.issn.1003-0034.2016.12.008
基金项目: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)
中文摘要:

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。
【关键词】骨关节炎  姜黄素  软骨细胞  代谢
 
JAK2/STAT3 signal pathway mediating curcumin in cartilage cell metabolism of osteoarthritis
ABSTRACT  

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 C57BL/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 protein expression 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.
KEY WORDS  Osteoarthritis  Curcumin  Chondrocytes  Metabolism
 
引用本文,请按以下格式著录参考文献:
中文格式:李旭升,陈慧,甄平,李慎松,周胜虎,田琦,石杰,何晓乐,刘军.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[J].中国骨伤,2016,29(12):1104~1109
英文格式:LI Xu-sheng,CHEN Hui,ZHEN Ping,LI Shen-song,ZHOU Sheng-hu,TIAN Qi,SHI Jie,HE Xiao-le,LIU Ju.JAK2/STAT3 signal pathway mediating curcumin in cartilage cell metabolism of osteoarthritis[J].zhongguo gu shang / China J Orthop Trauma ,2016,29(12):1104~1109
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