HPK1在缺血性脑损伤中的作用

目的观察HPK1对sD大鼠全脑缺血／再灌注后海马CA1区锥体细胞的作用。方法采用四动脉结扎法建立大鼠全脑缺血模型，缺血15min后分别灌注30min、3h、6h、24h、3天和5天。大鼠随机分为假手术组、缺血／再灌注组、缺血／再灌注给药组和缺血／再灌注溶剂对照组。缺血／再灌注给药组再分为2组，分别脑室注射100g／L的HPK1 AS—ODNs、HPK1 MS—ODNs，每24h注射1次，连续3天，在最后一次注射24h后行四动脉结扎全脑缺血。使用免疫沉淀和焦油紫染色法等技术检测相关信号蛋白的表达、活化水平及神经元细胞的死亡。结果在大鼠海马神经元中有HPK1的表达，脑室注射AS—ODNs大鼠海马CA1区存活锥体细胞明显增多。结论HPK1反义寡核苷酸对缺血／再灌注引起的海马神经元凋亡具有保护作用。

The role of HPK1 in ischemic brain injury

Objective To investigate the role of HPK1 in the pyramidal cells in CA1 region of the rat hippocampus after hrain ischemia/reperfusion. Methods Transient brain ischemia （ 15 rain） and reperfusion was induced by the four -vessel occlusion method （4- VO） to establish rat brain ischemia model, followed by reperfusion of 0 rain, 30 min, 3 h, 6 h, 24 h , 3 d and 5 d, respectively. Rats were randomly assigned to 4 groups： sham - operaiion group, isehemia/ reperfusion group, drug test group and vehicle control group. The drug test group was injected with 100 g/L HPK1 AS - ODNs, MS - ODNs into the cerebral ventricle, every 24 h for 3 days, and 24 h after the final administration was subjec- ted to 4 - VO. Immunoprecipitation and cresyl fast violet staining were employed to detect the expression of relevant mes- sage proteins, activation and the death of the hippocampal neurons. Results It was found that HPK1 was expressed in rat hippocampus neurons. Conclusions Administration of HPK1 antisense oligodeoxynucleotides can significantly pro- tect hippoeampus neurons from apoptosis without dose -dependence.