姜黄素对NASH肝细胞凋亡及JNK信号通路的影响

Study on the effect of nonalcoholic steatohepatitis on the curcumin apoptosis of hepatocyte and JNK pathway

目的:探讨姜黄素对非酒精性脂肪性肝炎(NASH)的抗肝细胞凋亡作用及其对JNK信号通路的影响。方法:将HL-7702细胞分为对照组、模型组、低剂量治疗组及高剂量治疗组,对照组予普通培养液培养,模型组培养液中加入浓度为1.0 mmol/L的游离脂肪酸(FFA)诱导NASH模型,高、低剂量治疗组在模型组的基础上分别加入浓度为10μmol/L、20μmol/L的姜黄素干预,48 h后采用流式细胞术检测细胞凋亡情况,Western Blot法检测p-JNK蛋白的表达情况。结果:模型组肝细胞的早期及总凋亡率均明显高于对照组(均P<0.05),高、低剂量治疗组与模型组相比,肝细胞早期及总凋亡率均明显降低(均P<0.05)。模型组肝细胞的p-JNK蛋白表达明显高于对照组(P<0.05),治疗组的p-JNK表达较模型组显著下降(P<0.05),且呈剂量相关。结论:姜黄素可抑制JNK的活化,这可能是其抗细胞凋亡、延缓NASH进展的机制之一。

Objective:To investigate the anti-apoptosis effects of curcumin on hepatocytes in nonalcoholic steatohepatitis and the influence on c-Jun N-terminal kinase(JNK)pathway.Methods:HL-7702 cells were divided into control group,model group,low dose treatment group,and high dose treatment group.Cells in the control group were cultured with the standard medium while those in other groups were incubated with 1mmol/L FFA(model group),and 1mmol/L FFA together with 10μmol/L,20μmol/L curcumin respectively(low and high dose treatment groups)for 48 hours.The rates of cell apoptosis were evaluated by flow cytometry,and the protein expressions of p-JNK were determined by Western blot.Results:The early and total apoptosis rates in the model group were significantly higher than those in the control group(P<0.05),while the two apoptosis rates were lower in low and high dose treatment groups than in the model group(P<0.05).The protein expression of p-JNK was significantly higher in the model group than in control group,while lower in treatment group than in model group(P<0.05),especially in the high dose treatment group.Conclusion:Curcumin can intervene in apoptosis of hepatocyte in nonalcoholic steatohepatitis,which may be related to its inhibition of the JNK pathway.