美金刚对大鼠蛛网膜下腔出血后脑血管痉挛的作用

The effects of memantine on cerebral vasospasm after subarachnoid hemorrhage in rats

目的:研究美金刚(MEM)对大鼠蛛网膜下腔出血(SAH)后脑血管痉挛的作用及其机制。方法:42只SD大鼠随机分为3组:假手术组(sham),蛛网膜下腔出血模型组(SAH),蛛网膜下腔出血给药组(SAH+MEM),采用颈内动脉穿刺法制作SAH大鼠模型。SAH+MEM组在手术3 h以及后续每天静脉给予一次美金刚,连续给药7 d。根据Garcia神经功能评分检测SAH大鼠的神经功能;尼氏染色和免疫组化染色观察大鼠皮层、海马区域的神经元细胞和星形胶质细胞;HE染色评估大鼠基底动脉痉挛程度;Western Blot检测大鼠基底动脉p⁃Akt和内皮型一氧化氮合酶(eNOS)表达。结果:美金刚可以促进大鼠SAH后神经功能恢复(P<0.05),减少皮层和海马区神经元细胞变性(P<0.05)以及星形胶质细胞聚集(P<0.05),减轻脑组织损伤;与SAH组相比,美金刚治疗组大鼠基底动脉管腔增大(P<0.05),管壁变薄(P<0.05),改善血管痉挛;同SAH组相比,SAH+MEM组大鼠基底动脉p⁃Akt和eNOS蛋白表达上调(P<0.05)。结论:美金刚可能通过上调基底动脉p⁃Akt和eNOS蛋白表达,缓解SAH后血管痉挛,也具有改善脑组织损伤和神经功能障碍的作用。

Objective:To study the effects and mechanism of memantine(MEM)on cerebral vasospasm after sub⁃arachnoid hemorrhage(SAH)in rats.Method:Forty⁃two SD rats were randomly divided into 3 groups:Sham group,SAH group,SAH+MEM group,and the rat SAH model was made by internal carotid artery puncture.Three hours after surgery,rats in the SAH+MEM group were administered intravenously with MEM.The injections were administered once a day for 7 days.The neurological function of SAH rats was detected according to the Garcia neurobehavioral score.The number of neuron and astrocyte in cortex and hippocampus were assessed by Nissl staining and immunohisto⁃chemistry,respectively.The degree of basilar artery(BA)spasm in SAH rats was evaluate by HE staining.The expressions of p⁃Akt and endothelial nitric oxide synthase(eNOS)in BA was detected by Western Blot.Results:MEM treatment promoted the recovery of neurological dysfunction(P<0.05),reduced the degeneration of neurons(P<0.05)and aggregation of astrocytes(P<0.05),and alleviated brain tissue damage in SAH rats.Compared with the SAH model group,the rats in SHA+MEM group showed mild vasospasm,which is characterized by increased perimeter and reduced wall thickness of BA(P<0.05).Moreover,the expression of p⁃Akt and eNOS in BA was upregulated af⁃ter treatment memantine(P<0.05).Conclusion:MEM could attenuate vasospasm by up⁃regulating the expressions of p⁃Akt and eNOS in BA,which has the effect of improving brain tissue damage and neurological dysfunction.