氟伐他汀对大鼠脑缺血再灌注损伤后caspase-12、CHOP及JNK表达的影响  

Effect of fluvastatin on the expressions of caspase-12, CHOP and JNK in ischemia-reperfusion brain injury in rats

作　　者：朱海英[1] 陈艳萍[1] 马英文[1] 

机构地区：[1]济南市第四人民医院神经内一科,济南250031

出　　处：《中国医师杂志》2015年第11期1665-1668,共4页Journal of Chinese Physician

基　　金：济南市科技发展计划资助项目（201121025）

摘　　要：目的 观察氟伐他汀对大鼠脑缺血再灌注损伤后caspase-12、C/EBP同源蛋白（CHOP）及c-Jun-N-末端激酶（JNK）表达的影响.方法 42只大鼠按随机数字表法分为假手术（sham）组6只,缺血再灌注（I/R）组18只,他汀（Flu）组18只;后两组采用线栓法制模后于脑缺血2h再灌注24 h处理观察.采用免疫组织化学染色、免疫印迹法检测脑组织中caspase-12、CHOP及JNK的表达.结果 大鼠脑组织缺血再灌注24 h caspase-12、CHOP及JNK阳性细胞数及蛋白定量均明显增加（P＜0.01）;他汀组脑缺血再灌注24 h caspase-12、CHOP的阳性细胞数及蛋白定量较缺血再灌注组明显减少（均P ＜0.01）,而JNK表达在两组间比较差异无统计学意义（P＞0.05）.结论 caspase-12、CHOP及JNK在脑缺血再灌注损伤大鼠脑组织中的表达明显增加,表明内质网应激参与了脑缺血再灌注损伤的病理过程;氟伐他汀可抑制caspase-12、CHOP的表达,从而减轻脑缺血再灌注后的内质网应激.Objective To investigate the effect of fluvastatin on the expressions of caspase-12,CCAAT/enhancer-binding protein homologous protein（CHOP）, and c-Jun N-terminal kinases （JNK） in ischemia-reperfusion brain injury in rats.Methods Forty two rats were randomly divided into sham operation group （6 rats）, ischemia-reperfusion （I/R） group （18 rats）, and fluvastatin （Flu） group （18 rats）.The rats of I/R and Flu groups were molded by modified Longa intraluminal thread, then put to death at 2 h occlusion and 24 h reperfusion point.Expressions of caspase-12, CHOP, and JNK were detected with immunohistochemistry and Western blot.Results Immunohistochemistry and Western blot showed that the expressions of caspase-12, CHOP, and JNK were increased at 24 h reperfusion.Compared to I/R group, the expressions of caspase-12 and CHOP in Flu group were decreased significantly （all P 〈0.01）;and the expression of JNK had no difference between I/R and Flu groups（P 〉 0.05）.Conclusions The increased expression of caspase-12, CHOP, and JNK showed that endoplasmic reticulum stress was involved in the pathological process of ischemia-reperfusion brain injury.Fluvastatin could inhibit the expression of caspase12 and CHOP, and could delete endoplasmic reticulum stress （ERS） in ischemia-reperfusion brain injury.

关 键 词：普伐他丁/药理学 脑缺血/药物疗法/代谢 再灌注损伤/药物疗法/代谢 半胱氨酸天冬氨酸蛋白酶12/代谢 转录因子CHOP/代谢 JNK丝裂原活化蛋白激酶类/代谢 

分 类 号：R965[医药卫生—药理学]