牛磺酸联合安定治疗脑缺血再灌注损伤的实验研究

Combination of taurine and diazepam has neuroprotective effect on focal cerebral ischemia-reperfusion in rats

目的:研究牛磺酸联合安定对实验性脑缺血再灌注损伤大鼠的神经保护作用。方法:SD雄性大鼠随机分为假手术组、脑缺血再灌注损伤组、牛磺酸治疗组(200mg·kg-1)、安定治疗组(10mg·kg-1)、联合治疗组(牛磺酸100mg·kg-1+安定5mg·kg-1),每组12只。采用大脑中动脉栓塞法(MCAO)建立大鼠局灶性脑缺血模型,2h后拔出栓线形成再灌注,再灌注时各组分别给药,脑缺血再灌注损伤组注射等剂量的生理盐水,12h后各组重复注射1次。另分批实验同样5组动物,每组16只,分别于再灌注后10h给药,12h后重复治疗1次。各组中12只动物同先前5组于再灌注后48h观测神经行为学评分、脑梗死体积以及脑含水量测定。每组中余下4只大鼠,2周后行尼氏染色观察脑组织病理学改变。结果:与脑缺血再灌注损伤组相比,缺血后2h、12h联合治疗均能显著降低大鼠神经行为学评分、减少脑含水量、缩小脑梗死体积,同时能明显减轻海马神经元变性坏死(P<0.01或P<0.05),且其保护作用优于牛磺酸或安定单用组。结论:缺血性脑损害所致急、慢性损伤时牛磺酸联合安定具有明显的神经保护作用。

AIM：To observe the neuroprotective effect of combined treatment with taurine and diazepam against focal cerebral ischemia-reperfusion in rats. METHODS： Sixty male Sprague-Dawley rats were randomly divided into five groups： sham-operation group,vehicle group,taurine group （200 mg/kg,ip）,diazepam group （10 mg/kg,ip） and combined treatment group （taurine 100 mg/kg＋diazepam 5 mg/kg）. Focal cerebral ischemia was induced by the method of middle cerebral artery occlusion （MCAO） in rats,and reperfusion was emerged by removing the thread 2 h later. The drugs were administered respectively at the time of reperfusion,and subsequently repeated once 12 h later. The animals in vehicle group were intraperitoneally injected with isodose normal saline. The neurological deficit score,the brain water content and cerebral infarction were measured 48 h after MCAO. Other 5 group animals of focal cerebral ischemia-reperfusion （n=16 in each group） were set up as mentioned above and accepted treatments 10 h after reperfusion,likewise repeated once 12 h later. Twelve animals in each group were adopted the same management as the previous 5 groups at 48 h after MCAO. The remained 4 animals in each group were sacrificed until two weeks after MCAO to observe the histopathological changes by nissl staining. RESULTS： Compared to vehicle group,the animals in combined treatment group at 2 h or 12 h after MCAO both decreased the neurological deficit score,reduced the brain water content and infarct volume （P0.01 or P〈0.05）. The combined treatment significantly alleviated the neurological necrosis as well. The neuroprotective effect of the combined treatment was superior to that of using taurine or diazepam alone. CONCLUSION： These results suggest that combination of taurine and diazepam treatment has a coordinate neuroprotective effect on both the acute and chronic brain damage of focal cerebral ischemia-reperfusion.