脑缺血再灌注损伤中FKBP51对JNK通路的影响

目的 探讨脑缺血再灌注损伤中FK506结合蛋白51（FKBP51）对c-Jun氨基末端激酶（JNK）信号通路的影响.方法 采用四血管阻塞制作大鼠全脑缺血模型.将体质量220 ～ 250 g健康雄性清洁级SD大鼠按随机数字表法进行分组：假手术组、缺血再灌注组、FKBP51反义寡核苷酸组、FKBP51错义寡核苷酸组、溶剂对照组.假手术组仅电凝双侧椎动脉,不夹闭双侧颈总动脉;缺血再灌注组电凝双侧椎动脉,夹闭双侧颈总动脉;FKBP51反义寡核苷酸组在电凝双侧椎动脉时侧脑室注射反义寡核苷酸进行干预,连续注射3d,第4天夹闭双侧颈总动脉;FKBP51错义寡核苷酸组和溶剂对照组侧脑室分别注射等体积错义寡核苷酸和TE buffer.除假手术组外,其余各组均缺血15 min后复灌不同时间点,然后分别断头取海马用于免疫印迹和免疫沉淀,检测各组中FKBP51蛋白表达;检测FKBP51反义寡核苷酸对FKBP51蛋白表达和JNK、c-Jun磷酸化的影响.结果 （1）FKBP51反义寡核苷酸组的FKBP51蛋白表达量明显减少,与假手术组差异有统计学意义（P＜0.05）.（2）各组之间JNK总蛋白的表达差异均无统计学意义（P＞0.05）.假手术组p-JNK的表达量明显少于其他组,差异有统计学意义（P＜0.05）;缺血再灌注3h组、溶剂对照组、FKBP51错义寡核苷酸组p-JNK的表达较高,三组之间的差异无统计学意义（P＞0.05）;与FKBP51错义寡核苷酸组比较,FKBP51反义寡核苷酸组p-JNK的表达量较少,差异具有统计学意义（P＜0.05）.（3）各组之间c-Jun总蛋白的表达差异均无统计学意义（P＞0.05）.假手术组p-c-Jun的表达量明显少于其他各组,差异有统计学意义（P＜0.05）;缺血再灌注6h组、溶剂对照组、FKBP51错义寡核苷酸组p-c-Jun的表达量较高,三组之间的差异无统计学意义（P＞0.05）;与FKBP51错义寡核苷酸组比较,FKBP51反义寡核苷酸组p-c-Jun的表达量较少,差异具有统计学意义（P?

Effect of FKBP51 on JNK pathway in cerebral ischemia-reperfusion injury

Objective To investigate effect of FK506 binding protein 51 （FKBP51） on the c-JunN-terminal kinase （JNK） pathway in cerebral ischemia-reperfusion injury.Methods Transient global cerebral ischemia rat models were made by four-vessel method.Healthy male SD （Sprague Dawley） rats were randomly divided into：sham group,ischemia/reperfusion group （I/R group）,FKBP51 antisense oligonucleotide group （FKBP51 ASODN group）,FKBP51 missense oligonucleotide group （FKBP51 MSODN group）,and solvent control group （TE group）.The effect of FKBP51 ASODN on expression of FKBP51 protein and JNK was detected,and c-Jun phosphorylation was detected by Western blot.Results （1） FKBP51 protein expression in the FKBP51 ASODN group was reduced.The change of FKBP51 protein expression between the FKBP51 ASODN and sham groups was statistically significant （P ＜ 0.05）.（2） The expression differences of total JNK protein between all the groups were not statistically significant （P ＞ 0.05）.The expression of p-JNK in sham group was significantly less than the other groups （P ＜ 0.05）.The expressions of p-JNK in I/R 3d,TE,and FKBP51 MSODN groups were higher relative to Sham group; however,the differences among those three groups were not statistically significant （P ＞ 0.05）.The expression of p-JNK in FKBP51 ASODN group was significantly less than FKBP51 MSODN group （P ＜ 0.05）.（3） The expression differences of total c-Jun protein among all groups were not statistically significant （P ＞ 0.05）.The expression of p-c-Jun in sham group was significantly less than the other groups （P ＜ O.05）.The expressions of p-c-Jun in I/R 6 h,TE,and FKBP51 MSODN groups were higher relative to the sham group; however,the differences among those three groups were not statistically significant （P ＞ 0.05）.The expressions of p-c-Jun in FKBP51 ASODN group was significantly less than FKBP51 MSODN group （P ＜ 0.05）.Conclusions FKBP51 might activate JNK signaling pathway in cerebral ischemia-