盐酸埃他卡林对大鼠局灶性脑缺血后脑组织损伤和血液流变学的作用

Effects of Iptakalim hydrochloride on brain damage and blood rheology after focal cerebral ischemia in rats

目的研究盐酸埃他卡林(Ipt)对局灶性脑缺血后脑组织损伤保护作用及对血液流变学变化的影响。方法线栓法阻断SD大鼠大脑中动脉造成大鼠局灶性脑缺血。神经功能行为学评分参考Longa法,脑水肿形成检测采用Ellis公式,TTC染色法测定脑梗死范围。以DPH为荧光探针,采用荧光偏振法测定脑缺血6h后红细胞膜脂流动性,微粘度。结果脑缺血6h后,脑梗死范围达对侧脑半球的(24.75±6.66)%,预防性给予Ipt(1.0～4.0mg·kg-1,ip)可使脑梗死范围分别减少0.95%,6.6%(P<0.05),14.34%(P<0.01)。Ipt2.0和4.0mg·kg-1还可降低大鼠的神经功能行为评分及脑组织含水量。尼莫地平(Nim)0.3mg·kg-1也可减少脑梗死范围,降低脑组织含水量,降低神经功能行为评分。脑缺血6h后,红细胞变形能力下降,红细胞膜脂流动性降低,红细胞聚集程度及膜微粘度皆明显提高。预防性给予Ipt(2.0～4.0mg·kg-1,ip)及Nim0.3mg·kg-1可显著改善上述血液流变学指标。Ipt4.0mg·kg-1治疗作用的时间窗为3h,超过4h则治疗作用不显著。Nim0.3mg·kg-1治疗作用不明显。结论盐酸埃他卡林对局灶性脑缺血引起的脑损伤有一定的保护作用。

Aim To investigate the therapeutic effects of Iptakalim hydrochloride on brain damage and blood rheological changes induced by focal cerebral ischemia. Methods The rat model of focal cerebral ischemia was induced by middle cerebral artery occlusion using a suture method. Infarct size was evaluated by TTC staining. Neurological deficit score was evaluated by Longas method. Cerebral water content of the ischemic hemisphere was measured using wet-and-dry-weight method. The erythrocyte membrane fluidity was studied by the fluorescence polarization technique with DPH fluorescence probe. Results Infarct size of the brain was (24.75±6.66)% of contralateral hemisphere 6 h after focal cerebral ischemia.Pretreatment of Ipt 1.0～4.0 mg·kg -1,given inperitoneal,decreased the infarct size by 0.95%,6.6%(P<0.05),14.34%(P<0.01),respectively.The neurological deficit scores and the cerebral water content of the ischemic hemisphere were decreased by Ipt 2.0～4.0 mg·kg -1. Nimodipine 0.3 mg·kg -1 was also shown to reduce infarct size,neurological deficit scores and the cerebral water content. Focal cerebral ischemia for 6 h induced a significant decrease in erythrocyte deformabilitym and the fluidity of erythrocyte membrane,an increase in erythrocyte deformability and blood viscosity. Pretreatment of Ipt 2.0～4.0 mg·kg -1 and Nimodipine 0.3 mg·kg -1 can improve those index of blood rheology. The treatment window of opportunity of Ipt 4.0 mg·kg -1 was 3 h, neither the infarction volumes nor the deficits of sensorimotor behaviors was significantly improved when Ipt was given 4 h after the onset of permanent MCAO. Nimodipine 0.3 mg·kg -1 had no apparent treatment effect.Conclusion Iptakalim hydrochloride has protective effects on brain damage induced by focal cerebral ischemia.