丙泊酚衍生物cqmu-039对大鼠脑缺血再灌注损伤的保护作用及其对胶质细胞的影响

Protective role of propofol derivative compound cqmu-039 against cerebral ischemia-reperfusion injury of rats and its effects on gliocyte

摘要:

目的：观察丙泊酚衍生物cqmu-039对大鼠脑缺血再灌注损伤的保护作用，探讨 cqmu-039对脑缺血再灌注的保护机制。方法：雄性SD大鼠40只，随机分为假手术组、模型组、药物低、中、高（6、12、24 mg/kg）剂量组。模型组采用大脑中动脉栓塞法（middle cerebral artery occlusion，MCAO）线栓法制备脑缺血模型，缺血 2 h后再灌注 24 h取脑；假手术组与模型组采用相同手术方法，不植入栓子，药物处理组系在脑缺血模型建立后立即腹腔注射给药。结果：与模型组相比，药物处理组能显著改善大鼠神经缺损症状，其行为学评分降低，脑梗死面积明显缩小，皮层、CA1区与CA3区治疗组大鼠胶质细胞源性神经营养因子（lial cell line-derived neurotrophic factor，GDNF）阳性细胞数量明显增加（P<0.05，P<0.01，P<0.01）；CA1区、CA3区及齿状回胶质原纤维酸性蛋白（glial fibrillary acidic protein，GFAP）表达明显减少。结论：丙泊酚衍生物cqmu-039能通过提高GDNF表达同时降低GFAP的表达从而明显改善大鼠脑缺血再灌注时的损伤。

Abstract:

Objective：To investigate the protective effects of propofol derivative cqmu-039 on cerebral ischemia-reperfusion injury in SD rats and its mechanisms. Methods：A total of 40 SD rats were randomly divided into 5 groups：sham surgery group，cerebral is－chemia-reperfusion（IR） model group，low（6 mg/kg），medium（12 mg/kg） and high（24 mg/kg） doses of cqmu-039 groups. IR model was generated via the surgery of middle cerebral artery occlusion（MCAO） for 2 h and then reperfusion of blood for 24 h. Sham surgery was performed in the same way as IR model without implanting the embolus. Three different doses of cqmu-039 were injected imme－diately after the IR surgery was performed. Protective effects of cqmu-039 were evaluated through the neurological behavioral score，2，3，5-triphenyltetrazolium chloride（TTC） staining and expressions of glial cell derived neurotrophic factor（GDNF） and glial fibril－lary acidic protein（GFAP） in the hippocampus. Results：Neuronal injury was significantly improved in cqmu-039 groups than in model group. In addition，lower neurological behavioral scores，smaller cerebral infarct size and higher expressions of GDNF in CA1，CA3 and cortex regions were observed in cqmu-039 groups than in model group（P<0.05，P<0.01，P<0.01）. Expressions of GFAP in CA1，CA3 and dentate gyrus regions in cqmu-039 groups were decreasent in a dose-dependent manner. Conclusions：Propofol deriva－tive cqmu-039 can effectively improve cerebral ischemia-reperfusion injury of rats through increasing expressions of GDNF and de－creasing expressions of GFAP.