L-电压门控钙通道在糖尿病大鼠局灶性脑缺血中的变化及意义

Change of L-type voltage-gated Ca^(2+) channel current during focal brain ischemia in diabetic rats

目的:检测单纯局灶性脑缺血和糖尿病局灶性脑缺血大鼠不同时间L-电压门控钙通道电流的变化,通过比较探讨其在糖尿病局灶性脑缺血中的意义。方法:应用高脂饮食联合链脲佐菌素(STZ)制备糖尿病大鼠模型,线栓法制备单纯局灶性脑缺血模型及糖尿病大鼠局灶性脑缺血模型,根据缺血不同时间分为正常假手术组、单纯脑缺血1 h、3 h、6 h、24 h;糖尿病假手术组、糖尿病脑缺血1 h、3 h、6 h、24 h共计10组。对单纯缺血24 h及糖尿病局灶性脑缺血24 h大鼠进行神经功能评分;应用全细胞膜片钳技术检测各组缺血周围皮层神经元细胞上电压门控钙通道电流的变化。结果:糖尿病组大鼠术后清醒较晚,肢体偏瘫程度重于单纯缺血组(P<0.05);随着缺血时间的延长,单纯局灶性脑缺血及糖尿病局灶性脑缺血各组L-电压门控钙通道电流呈逐渐增大趋势(P<0.05),其中糖尿病局灶性脑缺血各组电压门控钙通道电流分别高于单纯局灶性脑缺血各组(P<0.05)。结论:与正常大鼠局灶性脑缺血相比,糖尿病大鼠局灶性脑缺血加重的原因可能与膜上钙通道开放电流增大导致的细胞内钙超载有关。

AIM：To observe the change of L-type voltage-gated Ca2＋ channel current during focal brain ischemia in the normal rats and the rats with diabetes mellitus（DM）.METHODS： Combination of high-fat diet with streptozotocin（STZ） was used to establish DM animal model.The operation of middle cerebral artery occlusion（MCAO） with monofilament on the rats was performed.The animals were divided into sham operation group,MCAO 1 h group,MCAO 3 h group,MCAO 6 h group,MCAO 24 h group,DM sham operation group,DM＋MCAO 1 h group,DM＋MCAO 3 h group,DM＋MCAO 6 h group and DM＋MCAO 24 h group.The score of neural function was determined to judge the degree of palsy in the rats in MCAO 24 h group and DM＋MCAO 24 h group.The changes of L-type voltage-gated Ca2＋ channel current of cortex neurons during ischemia were measured using the whole-cell patch clamp technique.RESULTS： The rats in DM＋MCAO 24 h group awaked slowly,and the degree of semiplegia was more serious than that in the rats in MCAO 24 h group.The score of neural function in DM＋MCAO group was higher than that in MCAO group（P〈0.05）.The longer the ischemic time was,the higher L-type voltage-gated Ca2＋ channel current was observed in MCAO group and DM＋MCAO group（P〈0.05）.L-type voltage-gated Ca2＋ channel current in DM＋MCAO group was higher than that in MCAO group at each time point（P〈0.05）.CONCLUSION： The aggratation of ischemic injury during DM＋MCAO is probably associated with Ca2＋ overload induced by calcium channel opening and current increasing.