摘要
目的探讨蛋白激酶B(protein kinase B,Akt)/雷帕霉素靶分子(molecular target of rapamycin,mTOR)信号通路介导的小鼠海马区神经胶质细胞激活在心力衰竭(heart failure,HF)引起认知功能障碍中的作用。方法将22只成年雄性C57BL/6小鼠按随机数字表法分为两组:假手术组(Sham组,10只)、慢性心力衰竭组(HF组,12只)。HF组小鼠行左冠状动脉前降支结扎,Sham组小鼠仅开胸不结扎。造模后1个月,对两组小鼠进行超声心动图检查,记录其左室舒张末期内径、左室收缩末期内径、左室舒张末期容积、左室收缩末期容积、左室射血分数及左室缩短分数。随后进行水迷宫实验,记录逃避潜伏期、穿越平台次数和目标象限停留时间。水迷宫实验结束后处死小鼠,取两组小鼠心脏组织和海马组织。心脏组织进行马松染色,并用免疫组织化学法检测小鼠海马组织胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、离子化钙结合接头分子1(ionized calcium binding adapter molecule 1,Iba1)、少突胶质细胞转录因子2(oligodendrocyte lineage transcription factor 2,Olig2)水平;Western blot法检测海马组织Akt、磷酸化蛋白激酶B(p⁃Akt)、mTOR、磷酸化雷帕霉素靶分子(p⁃mTOR)水平。结果马松染色结果显示HF组小鼠心肌出现明显的纤维化,Sham组心肌呈现正常状态。与Sham组小鼠比较:HF组小鼠左室舒张末期内径、左室收缩末期内径、左室舒张末期容积、左室收缩末期容积明显增加(P<0.05),逃避潜伏期明显增长(P<0.05),海马组织GFAP、Iba1、Olig2、p⁃Akt/Akt、p⁃mTOR/mTOR水平明显升高(P<0.05),左室射血分数、左室缩短分数明显降低(P<0.05),穿越平台次数、目标象限停留时间减少(P<0.05)。结论慢性HF小鼠在造模1个月后出现了认知功能障碍,并伴有海马组织神经胶质细胞激活,且Akt/mTOR信号通路也呈现出激活状态。
Objective To explore the effect of mouse hippocampal glial activation mediated by the protein kinase B(Akt)/molec⁃ular target of rapamycin(mTOR)signaling pathway on cognitive dysfunction caused by heart failure(HF).Methods A total of 22 adult male C57BL/6 mice were divided into two groups according to the random number table method:a sham operation(Sham)group(n=10)and a heart failure(HF)group(n=12).Mice in the HF group underwent ligation of the left anterior descending of the coronary artery,while those in the Sham group only underwent thoracotomy without ligation.One month after modeling,echocardiography was performed to re⁃cord the left ventricular end⁃diastolic diameter,left ventricular end⁃systolic diameter,left ventricular end⁃diastolic volume,left ventricu⁃lar end⁃systolic volume,left ventricular ejection fraction and left ventricular fractional shortening.Then,the water maze test was per⁃formed.The escape latency,the number of crossing the platform,and the residence time in the target quadrant were recorded.After the wa⁃ter maze test,the mice were sacrificed and the heart tissues and hippocampal tissues were collected.The heart tissue was stained with Masson's trichrome,and the levels of glial fibrillary acidic protein(GFAP),ionized calcium binding adapter molecule 1(Iba1)and oligo⁃dendrocyte lineage transcription factor 2(Olig2)in hippocampal tissue were detected by immunohistochemistry.The levels of Akt,phos⁃phorylated Akt(p⁃Akt),mTOR and phosphorylated mTOR(p⁃mTOR)in hippocampal tissue were measured by Western blot.Results According to Masson staining,the HF group showed obvious fibrosis in the myocardium,while normal fibrosis was seen in the Sham group.Compared with the Sham group,HF group presented significant increases in the left ventricular end⁃diastolic diameter,left ventric⁃ular end⁃systolic diameter,left ventricular end⁃diastolic volume and left ventricular end⁃systolic volume(P<0.05),increases in escape la⁃tency(P<0.05),remarkable increases in the levels of
作者
吴亚男
钟锋
周凯意
刘柏杨
雷黎明
王晟
Wu Yanan;Zhong Feng;Zhou Kaiyi;Liu Baiyang;Lei Liming;Wang Sheng(School of Medicine,South China University of Technology,Guangzhou 510006,China;Department of Anesthesiology,GuangdongProvincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China;De-partment of Oncology,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000,China;Anaesthesia Center of BeijingAnzhen Hospital,Capital Medical University,Beijing 100029,China)
出处
《国际麻醉学与复苏杂志》
CAS
2023年第3期232-237,共6页
International Journal of Anesthesiology and Resuscitation
基金
国家自然科学基金地区科学基金项目(82160157)。
