异氟醚通过BMP4/Smad信号通路对自发性高血压大鼠脑损伤的作用机制研究  

Effect of Isoflurane on Cerebral Injury in Spontaneously Hypertensive Rats through BMP4/Smad Signaling Pathway

作　　者：杨雪梅 杨康明[1] 李娜[2] YANG Xuemei;YANG Kangming;LI Na(Ganzi Tibetan Autonomous Prefecture People′s Hospital,Ganzi 626000,Sichuan,China)

机构地区：[1]甘孜藏族自治州人民医院,四川甘孜626000 [2]海南省人民医院,海口572000

出　　处：《中西医结合心脑血管病杂志》2024年第4期640-645,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:探究异氟醚通过调节骨发生形态蛋白4(BMP4)及其下游Smad蛋白对自发性高血压大鼠(SHR)脑损伤的作用机制。方法:采用随机数字表法将48只SHR分为模型组、异氟醚组、阳性药物组、异氟醚+LDN193189组,健康大鼠作为健康对照组,每组12只。各组大鼠分别放入氧气箱中,健康对照组、模型组、阳性药物组大鼠通入特殊气体(30%O_(2)、70%N_(2))1 h,异氟醚组、异氟醚+LDN193189组通入混杂2%异氟醚的特殊气体1 h,通过麻醉气体检测仪检测异氟醚含量,确保异氟醚浓度始终保持在2%。通气结束后,异氟醚+LDN193189组大鼠腹腔内注射BMP4/Smad通路抑制剂溶液20μL(LDN193189,5 mg/kg),阳性药物组大鼠腹腔内注射缬沙坦溶液20μL(10 mg/kg),健康对照组、模型组、异氟醚组大鼠腹腔内注射等量的生理盐水。氧气箱通气实验及注射每日1次,持续10 d。无创血压检测仪检测尾动脉收缩压变化;神经学行为评分评价行为功能;脑含水量检测脑水肿程度;原位末端转移酶标记法(TUNEL)染色和尼氏染色观察海马组织病理学变化及神经元损伤情况;荧光定量聚合酶链式反应(PCR)及蛋白免疫印迹(Western Blot)法检测海马组织BMP4、Smad2 mRNA及蛋白表达水平。结果:与模型组比较,异氟醚组、阳性药物组、异氟醚+LDN193189组大鼠海马神经细胞凋亡减少,尼氏小体增多,血压、神经学评分、脑组织含水量显著降低,BMP4、Smad2 mRNA及蛋白表达量显著升高(P<0.05);与异氟醚组比较,异氟醚+LDN193189组大鼠神经细胞凋亡增多,尼氏小体急剧减少,血压、神经学评分、脑组织含水量显著升高,BMP4、Smad2 mRNA及蛋白表达量显著降低(P<0.05);异氟醚组与阳性药物组各项数据差异均无统计学意义(P>0.05)。结论:异氟醚可通过促进BMP4/Smad信号通路减轻SHR脑损伤。Objective:To explore the effect of isoflurane on brain injury in spontaneously hypertensive rats(SHR)by regulating bone morphogenetic protein 4(BMP4)and its downstream Smad protein.Methods:Forty-eight SHR rats were randomly divided into model group,isoflurane group,positive drug group,isoflurane+LDN193189 group,and healthy rats were used as healthy control group,with 12 rats in each group.Rats in each group were placed into oxygen tanks,healthy control group,model group and positive drug group were injected with special gas(30%O_(2),70%N_(2))for 1 h,isoflurane group and isoflurane+LDN193189 group were injected with special gas mixed with 2%isoflurane for 1 h,and isoflurane content was detected by anesthesia gas detector.Ensure isoflurane concentration was maintained at 2%at all times.After ventilation,rats in isoflurane+LDN193189 group were intraperitoneally injected with BMP4/Smad pathway inhibitor solution of 20μL(LDN193189,5 mg/kg),the positive drug group was intraperitoneally injected with 20μL(10 mg/kg)of valsartan solution,and the healthy control group,model group and isoflurane group were intraperitoneally injected with the same volume of normal saline water.Oxygen tank ventilation test and injection were once a day for 10 days.The changes of tail artery systolic blood pressure were detected by non-invasive blood pressure detector.Neurological behavior score was used to evaluate behavioral function.Cerebral water content was used to measured the degree of cerebral edema.The histopathological changes and neuronal injury of hippocampus were detected by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)and Nysch staining.Fluorescence quantitative polymerase chain reaction(PCR)and Western Blot were used to detect the mRNA and protein expression levels of BMP4 and Smad2 mRNA and protein in hippocampus.Results:Compared with the model group,the apoptosis of hippocampal nerve cells in isoflurane group,positive drug group and isoflurane+LDN193189 group decreased,the number of ni

关 键 词：自发性高血压 脑损伤 异氟醚 骨发生形态蛋白4 SMAD蛋白 

分 类 号：R544.1[医药卫生—心血管疾病]