盐酸戊乙奎醚抑制脂多糖致急性肺损伤大鼠肺组织p38丝裂原活化蛋白激酶的活化  

Penehyclidine hydrochloride inhibits activation of p38MAPK in rat lung tissue with ALI induced by LPS

作　　者：沈伟锋[1] 赵晓刚[1] 丁玲[2] 杨波[2] 江观玉[1] 

机构地区：[1]浙江大学医学院附属第二医院急诊中心,浙江杭州310009 [2]浙江大学药学院药理及毒理实验室,浙江杭州310031

出　　处：《中国病理生理杂志》2009年第3期551-554,共4页Chinese Journal of Pathophysiology

摘　　要：目的:观察盐酸戊乙奎醚(PHC)对脂多糖(LPS)致急性肺损伤(ALI)大鼠肺组织p38丝裂原活化蛋白激酶(p38MAPK)、c-jun氨基末端激酶(JNK)活化的影响。方法:SD大鼠随机分为对照组、LPS模型组(5mg/kgLPS,iv)和LPS+PHC高、中、低(3.0、1.0和0.3mg/kg)3个剂量组,每组6只,进行PHC对肺组织p38MAPK、JNK表达的量效性分析;另取大鼠在注入NS后即刻0(对照组)和注射LPS后2h、4h、6h和12h共5个时点,每时点6只,进行肺组织p38MAPK、JNK表达的时效性分析。蛋白免疫印迹法检测肺组织p38MAPK、JNK的表达。结果:LPS模型组大鼠肺组织磷酸化p38MAPK、JNK的表达显著高于对照组(P<0.05);PHC高剂量组显著抑制LPS诱导的大鼠肺组织磷酸化p38MAPK表达(P<0.05);PHC在造模后6h时最能有效抑制磷酸化p38MAPK上调。与LPS模型组相比,PHC高、中、低剂量组磷酸化JNK的表达均无显著差异(均P>0.05);造模后不同时点,PHC对磷酸化JNK的表达均无抑制作用。结论:PHC抑制LPS诱导的ALI大鼠肺组织p38MAPK活化,但不能抑制JNK活化,PHC对LPS诱导大鼠ALI的拮抗作用可能与其抑制p38MAPK的活化有关。AIM： To investigate the effects of penehyclidine hydrochloride （PHC） on lipopolysaccharide （LPS） induced activation of p38 mitogen - activated protein kinase （p38MAPK） and c - Jun N - terminal kinase （JNK） in lung tissue in rats. METHODS： Acute lung injury （ALI） was induced successfully by intravenous administraiton of LPS （5 mg/kg） in rats. PHC （3.0, 1.0, and 0. 3 mg/kg） was administered to rats 0. 5 h prior and then again concomitant with LPS exposure. Western blotting analysis was performed to determine the phosphorylations of p38MAPK and JNK in lung tissue at 6 h after LPS application. To examine whether the effects of PHC on activation of p38MAPK and JNK was in a time - dependent manner, lung tissues at 0 h, 2 h, 4 h, 6 h, and 12 h were collected for measuring the levels of phosphorylated p38MAPK and JNK. RESULTS： Challenge with LPS alone triggered the activation of p38MAPK and JNK in 2 h. Pretreatment with PHC effectively inhibited the activation of p38MAPK induced by LPS at 6 h. However, PHC did not efficiently inhibit the activation of JNK induced by LPS. CONCLUSION ： These results suggest that the protective effect of PHC in LPS - induced ALl in rats is partly responsible for the inhibition of the activation of p38MAPK by LPS.

关 键 词：急性肺损伤 盐酸戊乙奎醚 脂多糖类 P38MAP激酶 c—jun氨基末端激酶 

分 类 号：R363[医药卫生—病理学]