GABAA受体与地西泮的缺血后脑保护作用有关

研究GABAA受体是否参与地西泮的缺血后脑保护作用。SD雄性大鼠24只,用光化学法制作脑梗死模型。根据给药的不同将动物随机分为4组,每组6只。地西泮组腹腔注射地西泮10mg/kg;地西泮+bicuculline组腹腔注射地西泮10mg/kg和bicuculline2.1mg/kg;bicuculline组腹腔单独注射bicuculline2.1mg/kg;对照组腹腔注射等量的生理盐水。从术前24h开始注射,每8h一次,直至处死。术后动物存活24h,然后在深麻下灌流固定、取脑、切片。在Nissl染色的切片上计算最大脑梗死面积,用TUNEL染色计数梗死区凋亡细胞数。地西泮组最大脑梗死面积和TUNEL阳性细胞数明显少于其它三组(P<0.01)。地西泮的脑保护作用可被GABAA受体拮抗剂bicuculline部分抵消,因而地西泮可能部分通过GABAA受体发挥脑保护作用。

GABAA RECEPTOR IS INVOLVED IN THE PROTECTIVE EFFECT OF DIAZEPAM ON NEURONS AGAINST CEREBRAL ISCHEMIA

To elucidate the role of GABA_A receptor in the protective effect of diazepam on neurons against cerebral ischemia. Photothrombosis was carried out to produce a local cerebral ischemia in the parietal cortex of 24 male SD rats. The rats were randomly divided into 4 groups averagely according to reagents administered. The rats in the first group received an injection of 10 mg/kg of diazepam intraperitoneally; In the second group, 10 mg/kg of diazepam and 2.1 mg/kg of bicuculline were injected into the rats; In the third group, 2.1 mg/kg of bicuculline was injected into the rats; The control group only received an injection of same amount of saline. Drug administration was started 24 hours before surgery and performed once every 8 hours until the rats were sacrificed. Twenty-four hours after surgery, the rats were perfused with aldehyde and their brains were sectioned. The maximum infarction areas were measured in Nissl-stained sections and the numbers of apoptotic cells in the periphery of infarction areas was counted on TUNEL-stained sections. The maximum infarction areas were reduced following diazepam administration. The number of TUNEL-stained apoptotic cells was also decreased in diazepam groups compared to all others (P<0.01). The protective effect of diazepam against cerebral ischemia can be partly abolished by GABA_A receptor antagonist bicuculline. Thus, GABA_A receptor might play a role in the protective effect of diazepam.