c-Jun氨基末端激酶信号通路在血管紧张素Ⅱ诱导腹主动脉瘤小鼠模型中的作用机制研究  

Mechanism of the c-Jun N-terminal kinase signaling pathway in the angiotensin II-induced abdominal aortic aneurysm mouse model

作　　者：李会朋[1] 肖影[1] 王国华[1] 陈智年[1] LI Huipeng;XIAO Ying;WANG Guohua;CHEN Zhinian(Xinxiang Central Hospital,Xinxiang 453000,China)

机构地区：[1]新乡市中心医院,普通外科二,河南新乡453000

出　　处：《中国比较医学杂志》2020年第7期96-103,共8页Chinese Journal of Comparative Medicine

摘　　要：目的探讨c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)信号通路在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导腹主动脉瘤(abdominal aortic aneurysm,AAA)小鼠模型中的作用机制。方法将C57BL/6 ApoE-/-(ApoE knock out,ApoE KO)雄性小鼠随机分为3组,假性手术组、模型组和抑制剂组;假性手术组背部肩胛间皮下手术植入预装生理盐水微量缓释泵,模型组、抑制剂组小鼠背部肩胛间皮下手术植入AngⅡ的痕量缓释泵(1000 ng/(min·kg)),造模周期为28 d,抑制剂组术前48 h腹腔注射JNK抑制剂SP600125(2 mg/kg)1 mL/d进行预处理,假性手术组和模型组给予等体积的生理盐水。苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察小鼠炎性反应指标,双氯荧光素(2′,7′-dichlorfluorescein-diacetate,DCFH-DA)染色检测活性氧(reactive oxygen species,ROS)的荧光强度,蛋白免疫印迹检测p-JNK、p-c-Jun蛋白表达。结果与假性手术组相比,模型组小鼠AAA病理症状明显,AAA组织中绿色荧光明显增强,ROS含量明显升高,p-JNK及p-c-Jun的表达出现了明显的增强,差异均具有统计学意义(均P<0.05);与模型组相比,抑制剂组小鼠AAA病理症状相对好转,AAA组织中荧光强度明显减弱,ROS含量明显降低,p-JNK及p-c-Jun的表达水平明显降低,差异具有统计学意义(P<0.05)。结论JNK信号通路在血管紧张素Ⅱ诱导小鼠腹主动脉瘤模型中起着重要的调控作用,抑制该通路能抑制氧化应激反应,改善AAA症状。Objective To investigate the expression and significance of the JNK/c-Jun pathway in the angiotensin II-induced abdominal aortic aneurysm mouse model.Methods C57BL/6 Apoe-/-male mice were randomly divided into three groups:sham model,and inhibitor groups.Mice in the sham group were implanted with a preloaded saline microrelease pump in the subscapular scapula,whereas mice in model and inhibitor groups were implanted with an Ang II trace release pump(1000 ng/min·kg).The modeling cycle was 28 days.The inhibitor group was pretreated by intraperitoneal injection of 1 mL/day JNK inhibitor SP600125(2 mg/kg)for 2 days before surgery.Sham and model groups were administered an equal volume of normal saline.Hematoxylin-eosin staining was used to observe the inflammatory response index of mice.2′,7′-Dichlorofluorescein-diacetate(DCFH-DA)staining was used to detect the fluorescence intensity of reactive oxygen species(ROS).Western blotting was used to detect expression of p-JNK and p-c-Jun proteins.Results Compared with the sham group,pathological symptoms of AAA tissue in the model group were obvious.Green fluorescence in AAA tissue was enhanced significantly and ROS content was increased significantly.Expression levels of p-JNK and p-c-Jun in AAA tissues were enhanced significantly(all P<0.05).Compared with the model group,the pathological symptoms of AAA tissue were relatively improved.Green fluorescence in AAA tissue was weakened significantly and ROS content was decreased significantly.The levels of p-JNK and p-c-Jun in AAA tissues were decreased significantly(P<0.05).Conclusions The JNK signaling pathway plays an important role in regulation of angiotensin II-induced abdominal aortic aneurysm in mice.Inhibition of this pathway suppresses oxidative stress and improves AAA symptoms.

关 键 词：c-Jun氨基末端激酶信号通路 血管紧张素Ⅱ 腹主动脉瘤 作用机制 小鼠模型 

分 类 号：R-33[医药卫生]