JNK信号通路在慢性乙型肝炎患者外周血单个核细胞中的活化  

Role of the JNK signal pathway in activation-induced cell death in PBMC from patients with chronic hepatitis B

作　　者：侯炳旭[1] 冯丽英[1] 

机构地区：[1]河北医科大学第二医院消化科河北省消化病重点实验室河北省消化病研究所,河北省石家庄市050000

出　　处：《世界华人消化杂志》2011年第29期3075-3080,共6页World Chinese Journal of Digestology

摘　　要：目的:研究c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)信号通路在慢性乙型肝炎患者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)激活诱导细胞死亡(activation induced cell death,AICD)过程中的作用.方法:选取慢性乙型肝炎患者40例,采用完全随机化方法随机分为2组,慢性乙肝组(n=20),慢性乙肝+抑制剂组(n=20),选取健康对照组(n=20).体外分离培养PBMC,模拟细胞在体内的AICD过程,其中慢性乙肝+抑制剂组在重新刺激凋亡前用JNK特异性抑制剂SP60012520μmol/L预处理2h.应用Western blot检测各组中磷酸化JNK(p-JNK)、总JNK、磷酸化c-jun(p-c-jun)、Bim(bcl-2 interacting mediator of cell death)的表达,流式细胞术检测PBMC凋亡.结果:慢性乙肝组PBMC凋亡率高于健康对照组,也高于慢性乙肝+抑制剂组,差异有统计学意义(P<0.05).慢性乙肝+抑制剂组PBMC凋亡率高于健康对照组,差异有统计学意义(P<0.05).慢性乙肝组p-J N K的表达高于健康对照组(t=5.885,P<0.01),也高于慢性乙肝+抑制剂组(t=11.502,P<0.01).总JNK在三个组的表达无统计学差异.慢性乙肝组p-c-jun的表达高于健康对照组(t=5.477,P<0.01),也高于慢性乙肝+抑制剂组(t=12.899,P<0.01).慢性乙肝组Bim的表达高于健康对照组(t=9.133,P<0.01),也高于慢性乙肝+抑制剂组(t=10.086,P<0.01).慢性乙肝组PBMC凋亡率与p-JNK蛋白的表达成正相关(r=0.823,P<0.01).结论:JNK信号通路参与介导了慢性乙型肝炎患者PBMC的AICD过程,是其凋亡增多的机制之一.AIM： To study the role of the JNK signal pathway in activation-induced cell death （AICD） in peripheral blood mononuclear cells （PBMC） from patients with chronic hepatitis B （CHB）. METHODS： Forty CHB patients were randomly and equally divided into two groups： CHB group and CHB＋inhibitor group. The normal control group was composed of twenty healthy blood donors. PBMC were isolated, cultured in vitro, and used to stimulate AICD. The CHB＋inhibitor group was pretreated with the JNK specific inhibitor SP600125（20 μmol/L） for 2 h before re-stimulation of apoptosis. The expression of p-JNK, total JNK, p-c-Jun and Bim proteins was detected by Western blot, and the apoptosis of PBMC was measured by flow cytometry. RESULTS： The apoptosis rate of PBMC was significantly higher in the CHB＋inhibitor group than in the healthy control group, and in the CHB group than in the healthy control group and CHB＋inhibitor group （all P 0.05）. The expression of p-JNK, p-c-Jun and Bim was significantly higher in the CHB group than in the healthy control group and in the CHB＋inhibitor group （all P 0.01）. No significant differences were observed in the expression of total JNK among the three groups. The apoptosis rate of PBMC had positive correlation with the expression of p-JNK in CHB patients （r = 0.823, P 0.01）. CONCLUSION： The JNK signal pathway is involved in mediating AICD in PBMC from CHB patients.

关 键 词：慢性乙型肝炎 外周血单个核细胞 激活诱导细胞死亡 C-JUN氨基末端激酶 C-JUN Bim 

分 类 号：R512.62[医药卫生—内科学]