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作 者:李浩[1] 李晓淼[1] 沈奕[1] 王伟力[1] Li Hao;Li Xiaomiao;Shen Yi(Department of Orthopaedics,Nanyuan Hospital,Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 201112,China)
机构地区:[1]上海交通大学医学院附属仁济医院南院,201112
出 处:《医学研究杂志》2020年第10期62-66,共5页Journal of Medical Research
基 金:上海市卫生和计划生育委员会科研基金资助项目(201840273)。
摘 要:目的探讨瘦素通过JAK/STAT途径对IL-1β诱导的软骨细胞增殖和炎性反应的影响及机制研究。方法提取SD大鼠的软骨细胞并进行鉴定;CCK-8筛选瘦素最佳浓度;集落形成实验检测细胞增殖能力;ELISA检测炎性细胞因子(IL-6、IL-8、TNF-α)的表达;Western blot法检测JAK/STAT途径相关蛋白的表达。结果瘦素的最佳作用浓度为10、20、40ng/ml;瘦素呈剂量依赖性使IL-1β刺激诱导的软骨细胞的增殖能力增强(P<0.05),且抑制了由IL-1β刺激诱导的软骨细胞中炎性细胞因子的上调(P均<0.05)。此外,瘦素抑制IL-1β刺激诱导JAK/STAT途径的激活,JAK和STAT3蛋白的磷酸化水平降低(P均<0.05)。结论瘦素通过抑制JAK/STAT途径的激活,从而提高软骨细胞的增殖能力,抑制炎性反应,从而对骨关节炎具有潜在的治疗作用。Objective To investigate the effects and mechanisms of leptin on IL-1β-induced chondrocyte proliferation and inflammatory response through the JAK/STAT pathway.Methods Extraction and identification of chondrocytes from SD rats.CCK-8 was used to select the optimal concentration of leptin.Colony formation experiments was used to determine cell proliferation capacity.ELISA was used to detect the expression of inflammatory cytokines(IL-6,IL-8,TNF-α).Western blot was used to detect the expression of JAK/STAT pathway related proteins.Results The optimal concentration of leptin was 10,20,40 ng/ml.Leptin enhanced the proliferation of chondrocytes induced by IL-1βstimulation in a dose-dependent manner(P<0.05),and inhibited the up-regulation of inflammatory cytokines in chondrocytes induced by IL-1βstimulation(all P<0.05).In addition,leptin inhibited the activation of the JAK/STAT pathway induced by IL-1βstimulation,and reduced the phosphorylation levels of JAK and STAT3 proteins(both P<0.05).Conclusion By inhibiting the activation of the JAK/STAT pathway,leptin can increase the value-added capacity of chondrocytes,inhibit inflammatory response of chondrocytes,and thus has potential therapeutic effects on osteoarthritis.
关 键 词:瘦素 骨关节炎 增殖 炎症 JAK/STAT途径
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