【摘要】 目的 在小鼠骨性关节炎(OA)模型中观察Janus酪氨酸蛋白激酶2/信号转导子与转录激活子蛋白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,探讨JAK2/STAT3信号通路在此过程中的作用。方法 将10只C57BL/6小鼠随机分为两组,选择其中一组小鼠建立OA模型,3周后取材,培养软骨细胞作为实验组,其余小鼠正常培养细胞作为对照组。在对照组和实验组中分别加入JAK2/STAT3信号通路激动剂SC-39100,运用蛋白印迹法(Western blotting)检测各组细胞p-JAK2、p-STAT3、B淋巴细胞瘤-2(Bcl-2)蛋白和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)、细胞色素c氧化酶(COX)、丙二醛(MDA)改变。结果 与对照组相比,OA模型组软骨细胞p-JAK2、p-STAT3、Bcl-2蛋白的表达偏低(P<0.05)、Bax蛋白的表达水平偏高(P<0.05),且OA模型组软骨细胞SDH和COX的表达水平均偏低(P<0.05)、MDA的含量偏高(P<0.05);当OA模型组加入SC-39100后,p-JAK2、p-STAT3、Bcl-2表达均较OA模型组升高(P<0.05)、Bax蛋白表达下降(P<0.05),SDH和COX的表达水平均较OA模型组升高(P<0.05),MDA的含量较OA模型组降低(P<0.05);对照组中加入SC-39100后的各指标与加入SC-39100前比较,差异均无统计学意义(P>0.05);OA模型加入SC-39100组后的各指标与对照组加入SC-39100比较,差异均有统计学意义(P<0.05)。结论 JAK2/STAT3信号通路和OA中软骨细胞变化密切相关,JAK2/STAT3信号通路激活后可抑制软骨细胞的凋亡;当激活的JAK2/STAT3信号通路活化时会增加软骨细胞线粒体抗氧化应激能力。更多还原

【Abstract】 Objective To determine the effect of Janus activated tyrosine kinase 2 and signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway on the metabolism and mitochondrial oxidative stress in the chondrocytes of osteoarthritis(OA) mice in order to explore the role of the signaling pathway in this process.Methods Ten C57BL/6 mice were randomly and equally divided into OA model group and normal control group.In 3 weeks after the establishment of OA model,all mice were sacrificed and their knee joint synovium tissues were harvested to isolate chondrocytes.SC-39100,a JAK2/STAT3 Signaling pathway agonist,was used to treat the obtained chondrocytes from the both groups of mice.The expression of p-JAK2,p-STAT3,Bcl-2,Bax,succinate dehydrogenase(SDH),and cytochrome c oxidase(COX) was detected by Western blotting.The content and activity of malondialdehyde(MDA) were measured.Results Compared with the chondrocytes derived from control group,the OA chondrocytes had significantly lower protein levels of p-JAK2,p-STAT3 and Bcl-2,higher level of Bax,lower SDH and COX,and increased content of MDA(all P< 0.05).The treatment of SC-39100 enhanced the expression of p-JAK2,p-STAT3 and Bcl-2,decreased the expression of Bax,up-regulated the levels of SDH and COX,and reduced the content of MDA(all P< 0.05).However,the treatment had no effect on all indices in the chondrocytes from control group(all P>0.05).Significant differences were found in the above all indices between the OA chondrocytes after SC-39100 treatment and the chondrocytes from control group(P < 0.05).Conclusion The JAK2/STAT3 signaling pathway is closely associated with OA chondrocytes.Its activation can suppress apoptosis in chondrocytes and enhance the anti-oxidative stress capacity of chondrocyte mitochondria.更多还原