摘要
目的 探究miR-124在右美托咪啶(Dex)减轻缺血性卒中大鼠神经功能损伤中的作用。方法 将36只雄性SD大鼠分为假手术组(Sham组)、缺血性卒中组(MCAO组)、缺血性卒中+右美托咪啶组(MCAO+Dex组)各12只。取MCAO组与MCAO+Dex组大鼠构建大脑中动脉缺血模型,Sham组大鼠分离颈动脉,不插入线栓。MCAO+Dex组大鼠模型构建成功后连续腹腔注射Dex注射液50 mg/kg治疗3 d。模型构建后3 d,评估各组大鼠神经功能。将大鼠处死,取全血和缺血侧脑组织用于检测miR-124表达,取全脑组织行TTC染色检测各组大鼠脑梗死面积,取全脑组织行TUNEL染色检测各组大鼠神经细胞凋亡情况,取缺血侧脑组织行Western blot检测观察各组大鼠PI3K/Akt信号通路和凋亡相关蛋白表达情况。结果 与Sham组相比,MCAO组大鼠神经功能评分及脑梗死面积占比升高(P<0.01);与MCAO组相比,MCAO+Dex组大鼠神经功能评分及脑梗死面积占比降低(P<0.01)。与Sham组相比,MCAO组血浆和脑组织中miR-124表达均明显增加,脑组织神经细胞中TUNEL染色阳性细胞占比及Cleaved-caspase-3、Bax蛋白表达升高,脑组织PI3K、p-Akt、Bcl-2蛋白表达明显减少(P<0.01);与MCAO组相比,MCAO+Dex组血浆和脑组织中miR-124表达均进一步增加,脑组织神经细胞中TUNEL染色阳性细胞占比及PI3K、p-Akt、Bcl-2蛋白表达升高,Cleaved-caspase-3与Bax蛋白表达明显减少(P<0.05,P<0.01)。结论 Dex通过增加miR-124、PI3K/Akt信号通路蛋白表达,抑制凋亡相关蛋白表达,达到减轻缺血性卒中大鼠神经细胞凋亡、减少脑梗死面积、改善神经功能的目的。
Objective To explore the effect of miR-124 on Dexmedetomidine(Dex)in reducing neurological impairment in ischemic stroke rats.Methods A total of 36 male SD rats were divided into Sham group(Sham group),ischemic stroke group(MCAO group)and ischemic stroke+Dex group(MCAO+Dex group),with 12 rats in each group.MCAO group and MCAO+Dex group were used to establish middle cerebral artery ischemia model,and the carotid artery was separated from the rats in Sham group without insertion of thread plug.After the successful establishment of rat model in MCAO+Dex group,continuous intraperitoneal injection of Dex 50 mg/kg was given for 3 days.The neurological function of each group was evaluated at 3 d after the model was established.The rats were sacrificed,and the whole blood and whole brain tissues were collected for the detection of miR-124 expression.The neural function of each group was evaluated at 3 d after the model was established.The rats were sacrificed,and the whole blood and ischemic brain tissues were collected to detect the expression of miR-124.The whole brain tissues were collected for TTC staining to detect the infarct area of the rats in each group,and collected for TUNEL staining to detect the apoptosis of nerve cells in the rats in each group.Ischemic brain tissues were collected for Western blot to observe the PI3K/Akt signaling pathway and apoptosis-related protein expression of rats in each group.Results Compared with Sham group,the neurological function score and infarct area ratio of rats in MCAO group were increased(P<0.01).Compared with MCAO group,neurological function score and infarct area ratio of rats in MCAO+Dex group were decreased(P<0.01).Compared with Sham group,the expression of miR-124 in plasma and brain tissue of MCAO group was significantly increased,and the percentage of TUNEL stained positive cells and Cleaved caspase-3 and Bax protein expression were increased,while the expressions of PI3K,P-Akt and Bcl-2 in brain tissue were significantly decreased(P<0.01).Compared with MCAO group,the expression of miR-124 in plasma and brain tissue was further increased in MCAO+Dex group,and the ratio of TUNEL stained positive cells and Cleaved caspase-3 and Bax protein expression were increased,while expression of Cleaved caspase-3 and Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion By increasing the expression of miR-124 and PI3K/Akt signaling pathway protein,Dex can inhibit the expression of apoptosis-related proteins,which can reduce the apoptosis of nerve cells and the area of cerebral infarction,and improve the neurological function of ischemic stroke rats.
作者
王珊
崔晓光
周期
李媛
WANG Shan;CUI Xiaoguang;ZHOU Qi;LI Yuan(Department of Anesthesiology,the First Affiliated Hospital of Hainan Medical College,Haikou 570000,China)
出处
《临床误诊误治》
CAS
2023年第3期143-148,共6页
Clinical Misdiagnosis & Mistherapy
基金
海南省自然科学基金青年基金项目(820QN397)。
