GLP-1/GIP双靶点受体激动剂DA5-CH对脑缺血再灌注损伤大鼠脑组织的作用及其机制研究  

Effect and mechanism of dual GIP/GLP-1 receptor agonist DA5-CH on cerebral ischemia-reperfusion injury in rats

作　　者：董丽荣[1] 徐娜[1] 吕建东 Dong Li-rong;Xu Na;LüJian-dong(Department of Pharmacy,The Second Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075100,China;Department of TCM,The Second Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075100,China)

机构地区：[1]河北北方学院附属第二医院药剂科,河北张家口075100 [2]河北北方学院附属第二医院中医科,河北张家口075100

出　　处：《中国现代医学杂志》2023年第6期25-29,共5页China Journal of Modern Medicine

基　　金：河北省自然科学基金面上项目(No:H2019423074);张家口市重点研发计划项目(No:1921017D)。

摘　　要：目的研究胰高血糖素样肽-1/抑胃肽(GLP-1/GIP)双靶点受体激动剂DA5-CH对脑缺血再灌注损伤(I/R)大鼠脑组织的作用及其可能机制。方法将30只脑I/R大鼠随机分为模型组、DA5-CH组、DA5-CH+SB431542组,每组10只。另取10只大鼠仅做假手术(假手术组)。DA5-CH组腹腔注射10 nmol/kg DA5-CH;DA5-CH+SB431542组腹腔注射10 nmol/kg DA5-CH和5 mg/kg SB431542,假手术组、模型组腹腔注射等体积生理盐水。检测各组大鼠脑组织含水量;免疫组织化学染色检测海马CA1区神经核抗原(NeuN)阳性细胞数;Western blotting检测脑组织转化生长因子β1(TGF-β1)、Smad3、p-Smad3蛋白的表达。结果与假手术组比较,模型组脑组织含水量增加,海马CA1区每个视野NeuN阳性细胞数减少,脑组织TGF-β1、p-Smad3/Smad3蛋白表达升高(P<0.05);与模型组比较,DA5-CH组脑组织含水量降低,海马CA1区NeuN阳性细胞数增加,脑组织TGF-β1、p-Smad3/Smad3蛋白表达降低(P<0.05);与DA5-CH组比较,DA5-CH+SB431542组脑组织含水量增加,海马CA1区NeuN阳性细胞数减少,脑组织TGF-β1、p-Smad3/Smad3蛋白表达升高(P<0.05)。结论GLP-1/GIP双靶点受体激动剂DA5-CH可保护脑I/R大鼠神经功能,减少脑组织含水量及神经元坏死,减轻海马区病理改变,其作用机制可能与激活TGF-β1/Smads通路有关。Objective To study the effect of dual GIP/GLP-1 receptor agonist DA5-CH on cerebral ischemiareperfusion(I/R)injury in rats and the potential underlying mechanisms.Methods Thirty cerebral I/R injury rat models were randomly divided into model group,DA5-CH group,and DA5-CH+SB431542 group,with 10 rats in each group.Another 10 rats only underwent sham operation and were set as sham group.Rats in the DA5-CH group were intraperitoneally injected with DA5-CH at a dose of 10 nmol/kg,those in the DA5-CH+SB431542 group were intraperitoneally injected with DA5-CH at a dose of 10 nmol/kg and SB431542 at a dose of 5 mg/kg,while those in the sham group and model group were intraperitoneally injected with an equal volume of normal saline.The water content of the brain tissues of rats was detected.The number of neuronal nuclear antigen(NeuN)-positive cells in hippocampal CA1 area was determined by immunohistochemical staining.The protein expressions of transforming growth factorβ1(TGF-β1),Smad3,and p-Smad3 in brain tissues were detected by Western blotting.Results Compared with the sham group,the water content of brain tissues was increased,the number of NeuN-positive cells in each field of hippocampal CA1 area was decreased,and the protein expressions of TGF-β1and p-Smad3/Smad3 in brain tissues were increased in the model group(P<0.05).Compared with the model group,the water content of brain tissues was decreased,the number of NeuN-positive cells in each field of hippocampal CA1 area was increased,and the protein expressions of TGF-β1and p-Smad3/Smad3 in brain tissues were decreased in the DA5-CH group(P<0.05).Compared with DA5-CH group,the water content of brain tissues was increased,the number of NeuN-positive cells in each field of hippocampal CA1 region was decreased,and the protein expressions of TGF-β1and p-Smad3/Smad3 in brain tissues were increased in the DA5-CH+SB431542 group(P<0.05).Conclusions The dual GIP/GLP-1 receptor agonist DA5-CH can protect the neurological function of rats with cerebral I/R injury,reduce

关 键 词：脑缺血再灌注 胰高血糖素样肽-1/抑胃肽双靶点受体激动剂 DA5-CH 神经功能 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]