氨溴索对胃内容物吸入性肺损伤中c-Jun氨基末端激酶信号通路的影响  

Effects of Ambroxol on JNK Signaling Pathway in Gastric Aspiration Induced Lung Injury in Rats

作　　者：张衍民[1] 贾晓民[1] 赵杰[1] 李海泉[1] 马雷[1] 徐俊马[1] 杭文璐[1] 

机构地区：[1]徐州医学院第二附属医院呼吸内科,江苏徐州221006

出　　处：《中国呼吸与危重监护杂志》2015年第4期368-371,共4页Chinese Journal of Respiratory and Critical Care Medicine

摘　　要：目的探讨氨溴索对大鼠胃内容物吸入后损伤肺组织中c-Jun氨基末端激酶(JNK)信号通路的影响。方法 40只健康SD雄性大鼠随机分为对照组、损伤组、SP600125组和氨溴索组,每组10只。复制大鼠胃内容物吸入性肺损伤动物模型,SP600125组术前给予尾静脉注射JNK特异性抑制剂SP600125(3 mg/100 g),氨溴索组于损伤发生后2 h给予尾静脉注射氨溴索(50 mg/kg)。检测各组大鼠支气管肺泡灌洗液(BALF)中性粒细胞计数与丙二醛(MDA)活性、肺组织湿/干重比值(W/D)、髓过氧化物酶(MPO)活性变化。蛋白免疫印迹法(Western blot)检测肺组织中JNK、磷酸化JNK(p-JNK)及诱导型一氧化氮合酶(i NOS)的蛋白表达。光镜下观察肺组织结构变化。结果与对照组比较,损伤组BALF中性粒细胞计数与丙二醛(MDA)活性、肺组织W/D及MPO活性显著增加(均P<0.05);p-JNK与i NOS蛋白表达均显著增高(均P<0.05);肺组织出现明显病理组织学损伤。与损伤组比较,SP600125组和氨溴索组BALF中性粒细胞计数与MDA活性、肺组织W/D及MPO活性显著下降(均P<0.05);p-JNK与i NOS蛋白表达显著下降(均P<0.05);肺组织病理学损伤减轻。Western blot结果显示各组大鼠肺组织中JNK蛋白表达差异无统计学意义。结论 JNK参与胃内容物吸入性肺损伤炎症反应。氨溴索可能通过抑制JNK信号通路、抑制i NOS表达发挥抗炎、抗氧化保护作用。Objective To investigate the effect of ambroxol hydrochloride on c-Jun N-terminal kinase（ JNK） signal pathway in gastric aspiration lung injury. Methods Forty healthy male SpragueDawley rats were randomly divided into a control group,an injury group,a SP600125（ JNK specific inhibitor） group and an ambroxol group. The model of gastric aspiration lung injury was established by aspiration of gastric contents. The rats in the SP600125 group preoperatively received intravenous injection of JNK specific inhibitor SP600125（ 3 mg /100 g）. The rats in the ambroxol group received intravenous injection of ambroxol hydrochloride（ 50 mg / kg） 2 hours after the damage occurred. The neutrophil count and malondialdehyde（ MDA） activity in bronchoalveolar lavage fluid（ BALF）,the lung wet weight / dry weight ratio（ W / D）,and myeloperoxidase（ MPO） activity were measured. The protein expressions of JNK and phosphorylated JNK（ p-JNK） and inducible nitric oxide synthase（ i NOS） in lung tissue were detected by Western blot method. The changes of lung tissue structure were observed under light microscope. Results In the injury group,the neutrophil counts and MDA activity in BALF,W / D,MPO activity,p-JNK and i NOS protein expression increased significantly,lung tissue appeared obvious histopathological injury compared with the control group. In the SP600125 group and the ambroxol group,neutrophil count and MDA activity in BALF,lung W / D,MPO activity,p-JNK and i NOS protein expression were significantly decreased compared with the injury group（ P 0. 05）,and the damage of the lung tissue pathology was reduced. The expression of JNK protein in lung tissue was not different in all groups（ P 0. 05）. Conclusions JNK is involved in inflammatory reaction of gastric aspiration lung injury. The protective effect of ambroxol may be related to the inhibition of JNK signaling pathway and the inhibition of i NOS expression.

关 键 词：氨溴索 急性肺损伤 C-JUN氨基末端激酶 

分 类 号：R563[医药卫生—呼吸系统]