抑制c-Jun蛋白氨基末端激酶信号通路对内毒素血症大鼠肠屏障功能的保护作用  

The protective effects of inhibition of c-Jun N-terminal kinase signal pathway on the intestinal barrier in rats with endotoxemia

作　　者：陈传希[1] 欧阳彬[1] 赖箭波[2] 邱春芳[1] 管向东[1] 

机构地区：[1]中山大学附属第一医院重症医学科,广东510080 [2]深圳市人民医院重症医学科

出　　处：《中国危重病急救医学》2012年第6期327-329,共3页Chinese Critical Care Medicine

基　　金：国家自然科学基金（81071536）;教育部留学回国启动基金（20071108）;广东省科技计划项目（20108031600314）;中山大学5010计划项目资助（2007015）

摘　　要：目的探讨阻断细胞质内应激信号通路c-Jun蛋白氨基末端激酶（JNK）对内毒素血症大鼠肠屏障损伤的保护作用。方法24只雄性SD大鼠，按随机数字表法分为对照组、内毒素血症模型组、JNK抑制剂组3组，每组8只。对照组仅给予生理盐水2ml／kg＋JNK抑制剂SP600125的溶剂PPCES液2．5ml／kg；内毒素血症模型组静脉注射脂多糖（LPS）10mg／kg＋PPCES液2．5ml／kg；JNK抑制剂组静脉注射LPS10mg／kg＋JNK抑制剂SP600125iomg／kg。记录各组大鼠活动和生存情况；并于12h后取大鼠回肠，光镜下观察肠道黏膜病理改变；同时取血，采用酶联免疫吸附试验（ELISA）测定血浆D-乳酸含量。结果对照组大鼠活动正常，无死亡；模型组大鼠精神萎靡、活动减少，12h内死亡1只；JNK抑制剂组大鼠活动较模型组活跃，无死亡。回肠黏膜病理检查显示：与对照组相比，模型组大鼠回肠组织黏膜水肿，绒毛缩短，炎性细胞浸润；JNK抑制剂组回肠组织病变较模型组减轻。模型组大鼠血浆D-乳酸含量（μg／L）较对照组显著升高（943．8±439．6比227．9±130．0，P〈0．05）；JNK抑制剂能显著降低内毒素血症大鼠血浆D-乳酸含量（637．4±114．4比943．8±439．6，P〈0．05）。结论抑制细胞质内应激信号通路JNK能减轻内毒素血症大鼠肠屏障损伤。Objective To examine the protective effects of inhibition of c-Jun N-telninal kinase （JNK） stress signal pathway on the injured intestinal barrier in endotoxemic rats. Methods Twenty-four male Sprague Dwaley （SD） rats were randomly divided into control group, endotoxemia model group and JNK inhibitor group （n = 8 each ） to receive administration of： （1） normal saline 2 ml/kg ＋ PPCES 2.5 ml/kg ~vehicle of JNK inhibitor （SP600125）, control group; （2）lipopolysaccharide （LPS） 10 mg/kg ＋ PPCES 2.5 m]/kg （endotoxemia model group）; （3）LPS 10 mg/kg ＋ JNK inhibitor （SP600125） 10 mg/kg （JNK inhibitor group ）. The activity and survival rate of the rats were recorded. Ileum tissue samples were collected 12 hours after drug administration for pathological examination. Blood samples were collected at the same time for determination of concentration of D-lactate by enzyme linked immunosorbent assay （ELISA）. Results Rats in control group were active normally, and there was no death. The endotoxemic rats became lethargic and the activity was reduced, and a rat died within 12 hours after LPS injection. JNK inhibitor improved the general status and activity of the rats, and there was no death. Pathological examination showed there was edema of ileal mucosa, and shortening of villus and inflammatory cell infiltration in model group as compared with control group. JNK inhibitor greatly ameliorated the lesions compared with model group. The concentration of D-lactate （μg/L） in model group was significantly higher than that in control group （943.8± 439.6 vs. 227.9 ± 130.0, P〈0.05 ）. JNK inhibitor could decrease the plasma D-lactate concentration （637.4 ±114.4 vs. 943.8 ±439.6, P〈0.05）. Conclusion Inhibition of the JNK stress signal pathway could attenuate the intestinal harrier injmy in endotoxemic rats.

关 键 词：内毒素血症 肠屏障 c-Jun蛋白氨基末端激酶信号通路 D-乳酸 

分 类 号：R459.6[医药卫生—治疗学]