地黄梓醇对大鼠脑缺血再灌注损伤后PI3K/Akt/mTOR信号通路的影响  

Effects of Catalpol of Rehmannia Glutinosa on the PI3K/Akt/mTOR Signaling Pathway Following Ischemia-Reperfusion Injury in Rats

作　　者：乔园 吴启航 杨洁[1] QIAO Yuan;WU Qihang;YANG Jie(Institute of Chinese Materia Medica,Shaanxi Academy of Tranditional Chinese Medicine,Xi'an 710003,China)

机构地区：[1]陕西省中医药研究院中药研究所,陕西西安710003

出　　处：《中医药信息》2024年第12期6-10,共5页Information on Traditional Chinese Medicine

基　　金：陕西省自然科学基金资助项目(2019JQ-995);西安市创新能力强基计划-医学研究项目(22YXYJ0114)。

摘　　要：目的:基于PI3K/Akt/mTOR信号通路探究地黄梓醇对脑缺血再灌注损伤大鼠的神经保护作用。方法:36只SPF级雄性SD大鼠,随机分为假手术组、模型组和地黄梓醇组(5 mg/kg),每组12只。除假手术组外,模型组和地黄梓醇组采用线栓法复制大鼠脑缺血再灌注损伤模型,大鼠术后清醒后,地黄梓醇组腹腔注射地黄梓醇生理盐水溶液,假手术组和模型组腹腔注射等体积生理盐水,连续7 d,1次/d。随后采用Longa评分标准评估大鼠神经功能恢复情况;干/湿称重法检测实验大鼠脑含水量;ELISA法检测大鼠缺血侧脑组织丙二醛(malondialdehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)水平;蛋白免疫印迹法(Western blot)检测大鼠脑缺血侧皮层PI3K/Akt/mTOR通路相关蛋白表达情况。结果:与假手术组比较,模型组大鼠出现明显的神经功能缺损症状,神经功能缺损评分显著升高(P<0.01);与模型组比较,地黄梓醇组大鼠神经功能缺损评分显著降低(P<0.05)。与假手术组比较,模型组大鼠脑含水量明显增加(P<0.01),表现出一定的水肿症状;与模型组比较,地黄梓组大鼠脑含水量明显降低(P<0.01)。与假手术组比较,模型组大鼠缺血侧脑组织SOD水平明显降低、MDA含量明显升高(P<0.01);与模型组比较,地黄梓组大鼠缺血侧脑组织中SOD水平明显升高、MDA含量明显降低(P<0.01)。与假手术组比较,模型组大鼠缺血侧脑组织p-PI3K、p-Akt、p-mTOR蛋白水平升高(P<0.05,P<0.01);与模型组比较,地黄梓醇组p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白水平升高(P<0.05)。结论:地黄梓醇可明显改善模型组大鼠神经功能损伤,减轻脑水肿程度,显著上调脑组织中SOD、p-PI3K/PI3K、p-Akt/Akt和p-mTOR/mTOR的水平,显著下调MDA的水平。地黄梓醇对脑缺血再灌注损伤的保护作用可能是与促进PI3K/Akt/mTOR信号通路的激活有关。Objective:To explore the neuroprotective effects of Catalpol of Rehmannia Glutinosa based on the PI3K/Akt/mTOR signaling pathway in rats with brain ischemia-reperfusion injury.Methods:Thirty-six male SPF-grade SD rats were randomly divided into three groups:Sham surgery group,Model group,and Catalpol of Rehmannia Glutinosa group(5 mg/kg),with 12 rats in each group.Except for the Sham surgery group,the Model group and the Catalpol of Rehmannia Glutinosa group underwent a middle cerebral artery occlusion(MCAO)procedure to create a brain ischemia-reperfusion injury model.After the procedure,the Catalpol of Rehmannia Glutinosa group received intraperitoneal injections of Catalpol of Rehmannia Glutinosa in saline solution,while the Sham surgery and Model groups received intraperitoneal injections of saline.Treatments were administered daily for 7 days.Neurological function recovery was assessed using the Longa scoring system.Brain water content was measured using the dry/wet weight method.ELISA was used to measure malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity in the ischemic brain tissue.Western blot analysis was employed to assess the expression of proteins related to the PI3K/Akt/mTOR pathway in the ischemic brain cortex.Results:Compared to the Sham surgery group,the Model group exhibited significant neurological deficits with increased neurological impairment scores(P<0.01).The Catalpol of Rehmannia Glutinosa group showed significantly reduced neurological impairment scores compared to the Model group(P<0.05).Brain water content was significantly higher in the Model group compared to the Sham surgery group,indicating edema(P<0.01).The Catalpol of Rehmannia Glutinosa group had significantly reduced brain water content compared to the Model group(P<0.01).The Model group had decreased SOD levels and increased MDA levels in the ischemic brain tissue compared to the Sham surgery group(P<0.01).The Catalpol of Rehmannia Glutinosa group had significantly increased SOD levels and decreased MDA levels comp

关 键 词：地黄梓醇 脑缺血再灌注损伤 神经功能 氧化应激 PI3K/Akt/mTOR信号通路 

分 类 号：R285.5[医药卫生—中药学]