西地那非对脑出血所致病理损伤和神经功能缺损的影响OACSTPCD
Effect of sildenafil on pathological damage and neurological deficits after intracerebral hemorrhage
目的 探讨血管活性药物西地那非(SDNF)对脑出血小鼠脑影像、病理损伤及神经功能的影响.方法 24只2~3月龄C57Bl/6小鼠,采用脑立体注射胶原酶法构建脑出血(ICH)模型,随机分为溶剂组、SDNF组,分别给予生理盐水或等体积0.5 mg/kg的SDNF连续灌胃7d,之后分别在第3、7、14天进行mNSS神经功能评分,第7天采用脑磁共振检查脑血肿体积,激光散斑脑血流仪检测脑血流.造模后第14天处死小鼠,采用血红蛋白检测试剂盒检测脑内血红蛋白含量,采用免疫荧光法检测血肿周围血管内皮细胞标记CD31的表达量.结果 SDNF组小鼠mNSS评分在第7、14天的评分(分别为6.17±1.19、2.75±1.21)较溶剂组(分别为8.50±1.12、4.83±0.93)显著减小(F 交互=6.49,P<0.001).SDNF组小鼠脑内血肿体积、校正脑组织水肿率在第7天(分别为2.94±1.05、5.37±1.26)较溶剂组(分别为6.03±1.23、8.01±1.75)显著减小(t值分别为4.66、2.99,均P<0.05),相对脑血流量(82.50±5.17)显著高于溶剂组(73.50±7.56,P<0.05).SDNF治疗组小鼠脑内血红蛋白含量在第14天(36.98±12.31)显著小于溶剂组(66.00±17.21,P<0.05),病理结果显示SDNF治疗组小鼠脑内血管内皮标记物CD31的表达量(34.72±8.22)显著高于溶剂组(23.00±8.60,P<0.05).结论 SDNF可减轻小鼠脑出血后神经功能缺损症状,改善脑血流,促进血肿吸收,降低脑内血红蛋白的含量,促进血管内皮细胞再生,在脑出血治疗中具有潜在的临床应用价值.
Objective To investigate the effects of silndenafil on brain damage and neurological function in mice with cerebral hemorrhage.Methods Twenty-four C57Bl/6 mice aged 2 to 3 months were used to construct an intracerebral hemorrhage(ICH)model using stereotaxic frame injection of collagenase into the brain.The ICH mice were randomly divided into the vehicle group and the sildenafil group,and were respectively given normal saline and equal volume of 0.5 mg/kg sildenafil in normal saline by oral dosage in 7 days following ICH.Then,mNSS scores were performed on days 3,7 and 14.Brain magnetic resonance imaging was performed on day 7 to detect cerebral hematoma volume,and laser speckle flowmeter was used to analyze cerebral blood flow.The mice were sacrificed on the 14th day after modeling,and the hemoglobin content in the brain was detected using a hemoglobin detection kit.Results The neurological deficit scores of the mice in the sildenafil treatment group(6.17±1.19,2.75±1.21)were significantly smaller than those in the vehicle group(8.50±1.12,4.83±0.93)on days 7 and 14(F=6.49,P<0.001).The intracerebral hematoma volume and the corrected brain swelling in the sildenafil group(2.94±1.05,5.37±1.26)were significantly smaller than that of the vehicle-treated group(6.03±1.23,8.01±1.75)on day 7(t=4.66,2.99,respectively,P<0.05).Relative cerebral blood flow in the sildenafil group(82.50±5.17)was significantly higher than that of the vehicle group(73.50±7.56,P<0.05).The hemoglobin content in the brain of mice in the sildenafil treatment group(36.98±12.31)was significantly reduced compared with the vehicle group(66.00±17.21,P<0.05).In addition,pathology investigation revealed that the immunoactivity of the endothelial cell marker CD31 was significantly higher in the SDNF group(34.72±8.22)than that of the vehicle treated group(23.00±8.60)on the 14th day(P<0.05).Conclusion Sildenafil can improve the symptoms of neurological deficit in mice after cerebral hemorrhage,improve cerebral blood flow,promote hematoma absorption,and reduce the content of hemoglobin in the brain.Sildenafil has potential clinical application value in the treatment of cerebral hemorrhage.
郑娜;张丹丹;刘希;李文才
郑州市第三人民医院,河南 郑州 450000郑州大学第一附属医院,河南 郑州 450052
脑出血西地那非PDE5抑制剂磁共振脑血流病理损伤血红蛋白
Cerebral hemorrhageSildenafilPDE5 inhibitorMRICerebral blood flowpathological damageHemoglobin
《中国实用神经疾病杂志》 2024 (005)
542-546 / 5
河南省高等学校重点科研项目(编号:22B320013)
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