戊乙奎醚预处理对脓毒症小鼠肺损伤时MAPK信号转导通路的影响

目的 探讨戊乙奎醚(PHC)预处理对脓毒症小鼠肺损伤时丝裂原活化蛋白激酶(MAPK)信号转导通路的影响.方法 健康雌性昆明小鼠105只,体重20～25 g,随机分为3组(n=35):假手术组(S组)、脓毒症(CLP)组和戊乙奎醚(PHC)组.采用盲肠结扎并穿孔法制备脓毒症模型.PHC组于造模前1 h腹腔注射戊乙奎醚0.45 mg/kg,s组和CLP组于造模前1 h注射等容量生理盐水.于造模后即刻测定肺微血管通透性;造模后12 h时进行动脉血气分析,观察肺组织病理结果,测定肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和磷酸化的p38丝裂原活化蛋白激酶(p38MAPK)、细胞外信号调节激酶(ERK1/ERK2)和c-jun氨基末端蛋白激酶(JNK)表达.结果 与S组比较,CLP组PaO2、PaO2/FiO2和pH值降低,肺微血管通透性和肺组织MDA含量升高,SOD活性降低,磷酸化的p38MAPK、ERK1/ERK2和JNK表达上调(P<0.05或0.01);与CLP组比较,PHC组PaO2、PaO2/FiO2和pH值升高,肺微血管通透性和肺组织MDA含量降低,SOD活性升高,磷酸化的p38MAPK和ERK1/ERK2表达下调(P<0.05或0.01).结论 戊乙奎醚预处理可通过抑制MAPK信号转导通路(p38MAPK和ERK1/ERK2)的激活,从而减轻脓毒症小鼠肺损伤.

Effects of penehyclidine preconditioning on MAPK pathway in lung injury induced by sepsis in mice

Objective To investigate the effects of penehyclidine preconditioning on mitogen-activated protein kinase (MAPK) pathway in the lung injury induced by sepsis in mice. Methods Methods One hundred and five healthy female mice weighing 20-25 g were randomly divided into 3 groups (n=35 each):group Ⅰ sham operation (S);group Ⅱ sepsis and group Ⅲ PHP + sepsis. Sepsis was produced by cecal ligation and puncture (CLP). In group Ⅲ penehyclidine 0.45 mg/kg was administered intraperitoneally 1 h before CLP. Pulmonary microvascalar permeability was determined with intravenous Evans blue given instantly after surgery in 10 animals in each group. Arterial blood gas analysis was performed at 12 h after CLP, and the animals were killed. The lungs were immediately removed for histological examination with light microscope and determination of SOD activity, MDA content, and expression of phosphorylated p38 MAPK, ERK1/ERK2 and JNK in the lung tissue. Results Compared with control group (S), CLP significantly decreased PaO2, PaO2,/FiO2 and pH;increased pulmonary micrevascalar permeability, MDA content and expression of p38 MAPK, ERK1/ERK2 and JNK in the lung tissue. PHP significantly attenuated CLP-induced changes in blood gas, pulmonary microvascular permeability, MDA content and expression of p38 MARK, ERK1/ERK2, and JNK in the lung tissue. Conclusion Penehyclidine preconditioning can ameliorate lung injury induced by sepsis through inhibition of MAPK (p38 MAPK and ERK1/ERK2) activation.