硫化氢供体在小鼠缺血性脑卒中模型抗再灌注损伤研究

Study on the anti-reperfusion effect of H2S donor in mice with ischemic stroke

目的探讨硫化氢(H2S)供体靶向抗缺血性脑卒中的脑部保护机制.方法60只C57B1/6雌性小鼠,采取MCAO方法建立缺血性脑卒中模型,随机分为3组:药物组(H2S供体组),假手术组,空白组,每组20只.静脉注射4-氯-7-硝基苯并-2-氧杂-1,3-二唑;4-氯-7-硝基苯呋咱(NBD)荧光标记的H2S供体.蛋白质印迹法(Western blot)检测小鼠脑组织应急损伤指标S-100B变化,神经功能缺损评分,脑组织梗死面积及脑组织含水量测定评估H2S供体治疗前后小鼠脑组织形态及功能变化.结果Western blot结果显示,药物组S-100B表达较假手术组降低,差异有统计学意义(t=4.120,P<0.05).H2S供体及生理盐水干预脑卒中模型后,与假手术组脑梗死面积(43.0%,42.5%)比较,H2S供体药物组脑梗死面积(30.0%,31.5%),脑卒中后脑梗死面积有减少.3组小鼠脑组织水含量减少,分别为76.5%、84%、78.5%,差异比较均有统计学意义(t=3.027,P<0.05).假手术组神经功能缺失评分(1.98±0.76)、(1.97±0.81),H2S供体药物组神经功能缺失评分(1.01±0.39)、(1.15±0.32),两组差异有统计学意义(t=2.561,P<0.05).结论H2S供体降低卒中后脑缺血再灌注损伤S-100B表达,减轻脑梗死面积及脑水肿体积,从而改善神经功能,减轻脑缺血性损伤.

Objective To explore the brain protective mechanism of H2 S targeted anti-ischemic stroke.Methods 60 C57BL/6 female mice were randomly divided into three groups:drug group(H2S donor group),sham operation group and blank group,with 20 rats in each group.4-Chloro-7-nitro-1,2,3-benzoxadiazole(NBD)labeled H2S donors were injected intravenously.Western blotting was used to detect mice model on the expression changes of S-100B gene;Neurological deficit score,infarct area and water content of brain tissue were evaluated the treatment efficency.Results Western blotting re・suits showed that the expression of S-100B in the drug group was lower than that in the sham operation group(t=4.120,P<0.05).Compared with sham operated group(43%,42.5%),the cerebral infarc・tion area of mice in drug group(30%,31.5%)was reduced.The water volume of mice brain tissue in the three groups decreased,76.5%,84%and 78.5%respectively,the difference was statistically significant(t=3.027,P<0.05).The scores of neurological deficit in sham operation group(1.98±0.76),(1.97±0.81)and H2S donor drug group(1.01±0.39),(1.15±0.32)were statistically significant(t=2.561,P<0.05).Conclusion H2S donor can reduce the expression of S-100B,reduce the area of cerebral infarction and the volume of cerebral edema,improve the neurological function and reduce the cerebral ischemic injury.