人尿激肽原酶对大鼠局灶性脑缺血再灌注损伤的保护作用及对Caspase-3表达的影响  

Protective function of human urinary kallidinogenase in rats after focal cerebral ischemic reperfusion and its effect on caspase-3 expression

作　　者：陆伶俐[1] 刘振华[1] 谢惠芳[1] 宋学萍[1] 魏继鹏[1] 

机构地区：[1]南方医科大学珠江医院神经内科,广州510280

出　　处：《中华神经医学杂志》2012年第9期887-890,共4页Chinese Journal of Neuromedicine

摘　　要：目的观察人尿激肽原酶（HUK）对局灶性脑缺血再灌注损伤大鼠神经细胞凋亡及Caspase-3表达的影响。方法66只SD大鼠按随机数字表法分为假手术组（n=6）、缺血再灌注损伤组和HUK处理组，后两组又按不同观察时间点分为再灌注6h、12h、24h、72h、168h共5个亚组fn=6）。缺血再灌注损伤组和HUK处理组采用线栓法建立大鼠大脑中动脉局灶性脑缺血再灌注损伤模型，HUK处理组按浓度17．5×10^-3PNAU／mL，1．0mL／kg，于再灌注后3h尾静脉注射给药，1次／d。采用TUNEL法及免疫组化染色检测各组大鼠脑组织中凋亡细胞及Caspase-3阳性细胞的数量变化。结果脑缺血再灌注损伤后6h即有细胞凋亡．于24h达到高峰，至168h仍可见凋亡细胞。Caspase-3阳性细胞表达均于再灌注24h达高峰，至168h仍有较多表达。除168h时间点外，其余各时间点HUK处理组大鼠神经细胞凋亡数量、Caspase-3阳性细胞数量均明显低于缺血再灌注损伤组，差异均有统计学意义（P〈0．05）。结论HUK在大鼠局灶性脑缺血再灌注损伤早期（6～72h）时能抑制细胞凋亡，推测与其减少Caspase-3的表达有关。Objective To study the effect of human urinary kallidinogenase （HUK） on neural cell apoptosis in rats after focal cerebral ischemia-reperfusion （FCIR） injury and on Caspase-3 expression. Methods Sixty-six SD rats were randomly divided into sham-operated group （n=6）, ischemic-reperfusion group and HUK treatment group. The latter 2 groups were subdivided into 6, 12, 24, 72 and 168 h reperfusion groups （n=6）. Middle cerebral artery occlusion models of transient focal cerebral ischemia in the latter 2 groups were established by suture-occluded method. Rats of the HUK treatment group were given tail vein injection of HUK once daily at dosage of 17.5×10^-3 PNAU/mL and at 1.0 mL/kg manner 3 h after reperfusion. The numbers of apoptotic cells and Caspase-3 positive cells in the cerebral cortex were evaluated with terminal dUTP nick end labeling （TUNEL） assay and immunohistochemistry. Results Cell apoptosis was noted 6 h after the focal cerebral ischemia-reperfusion, reaching its peak level at 24 h, and the apoptotic cells could still be seen at 168 h after the injury. And the expression of Caspase-3 positive cells peaked at 24 h after the injury, and high expression was still noted at 168 h after the injury. The levels of apoptotic cells and the expression of Caspase-3 positive cells in HUK treatment group at different time points （except for 168 h subgroup） decreased significantly as compared with those in ischemic-reperfusion group （P〈0.05）. Conclusion HUK may decrease the number of apoptotic cells in the initial 72 h of FCIR injury by down-regulating the Caspase-3 expression.

关 键 词：人尿激肽原酶 脑缺血再灌注 细胞凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]