首页|右美托咪定通过α7nAChR介导的PI3K/Akt通路改善糖尿病大鼠术后认知功能

右美托咪定通过α7nAChR介导的PI3K/Akt通路改善糖尿病大鼠术后认知功能

Dextrmedetomidine Improves Postoperative Cognitive Function of Diabetes Rats Through α7nAChR Mediated PI3K/Akt Pathway

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目的 研究右美托咪定对糖尿病大鼠术后认知功能的影响及其机制.方法 将30只SD大鼠随机分为对照组(CG组)、糖尿病组(DM组)、糖尿病+右美托咪定组(DM+Dex组)、糖尿病+右美托咪定组+甲基牛扁亭柠檬酸盐组(DM+Dex+MLA组)和糖尿病+右美托咪定+LY294002组(DM+Dex+LY组).CG组为正常对照处理;其余各组糖尿病造模.DM+Dex组、DM+Dex+MLA组和DM+Bex+LY294002组于麻醉前腹腔注射右美托咪定;DM+Dex+MLA组在输注右美托咪定前腹腔注射MLA;DM+Dex+LY组在输注右美托咪定前腹腔注射LY294002.各组大鼠麻醉后,行剖腹探查术.手术后1周进行水迷宫实验.处死大鼠后分离其海马组织,Western blot检测海马组织中α7nAChR、p-PI3K、p-Akt的相对表达量,HE染色观察海马组织损伤情况.结果 与CG组相比,DM组大鼠Morris水迷宫实验找到平台所需时间显著增加(P<0.05),平台穿越次数显著减少(P<0.05),海马组织中α7nAChR、p-PI3K、p-Akt蛋白表达明显降低(P<0.05),DM组海马组织神经元萎缩、坏死,排列紊乱,部分神经元细胞核固缩、深染,甚至消失;与DM组相比,DM+Dex组大鼠找到平台所需时间显著缩短(P<0.05),平台穿越次数显著增加(P<0.05),海马组织中α7nAChR、p-PI3K、p-Akt蛋白表达明显升高(P<0.05),DM+Dex组较DM组海马损伤明显减轻;而右美托咪定的作用可被α7nAChR的抑制剂即MLA和PI3K抑制剂LY294002部分逆转.结论 右美托咪定通过α7nAChR介导的PI3K-Akt信号通路改善糖尿病大鼠术后认知功能.
Objective To study the effect of dexmedetomidine on postoperative cognitive function in dia-betes rats and its mechanism.Methods Thirty SD rats were randomly divided into control group(CG group),diabetes group(DM group),diabetes+dexmedetomidine group(DM+Dex group),diabetes+dexmedetomi-dine group+methyl niupingting citrate group(DM+Dex+MLA group)and diabetes+dexmedetomidine+LY294002 group(DM+Dex+LY group).The CG group was treated as a normal control group;Diabetes model was established in other groups.The DM+Dex group,DM+Dex+MLA group,and DM+Dex+LY294002 group received intraperitoneal injection of dexmedetomidine before anesthesia;The DM+Dex+MLA group re-ceived intraperitoneal injection of MLA before infusion of dexmedetomidine;The DM+Dex+LY group received intraperitoneal injection of LY294002 before infusion of dexmedetomidine.After anesthesia,each group of rats underwent laparotomy exploration.Conduct a water maze experiment one week after surgery.After euthanizing the rats,the hippocampal tissue was isolated,and the relative expression levels of α 7nAChR,p-PI3K,and p-Akt in the hippocampal tissue were detected by Western blotting.HE staining was used to observe the dam-age to the hippocampal tissue.Compared with the CG group,the Morris water maze experiment in the DM group showed a significant increase in the time required to find the platform(P<0.05),a significant decrease in the number of platform crossings(P<0.05),and a significant decrease in the expression of α 7nAChR,p-PI3K,and p-Akt proteins in the hippocampus(P<0.05).In the DM group,neurons in the hippocampus showed atrophy,necrosis,disordered arrangement,and some neurons had nuclear condensation,deep staining,or even disappearance;Compared with the DM group,the DM+Dex group rats showed a significant decrease in the time required to find the platform(P<0.05),a significant increase in the number of platform crossings(P<0.05),a significant increase in the expression of α 7nAChR,p-PI3K,and p-Akt proteins in the hip-pocampus(P<0.05),and a significant reduction in hippocampal damage compared to the DM group through HE staining;The effect of dexmedetomidine can be partially reversed by inhibitors of α 7nAChR,namely MLA and PI3K inhibitors LY294002.Conclusion Dextrmedetomidine can improve the postoperative cognitive func-tion of diabetes rats through the PI3K Akt signal pathway mediated by α 7 nAChR.

diabetescognitive impairmentdexmedetomidinePI3K Akt signaling pathway

赵梦玉、白栓成

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包头医学院中心临床医学院,内蒙古包头 014010

包头市中心医院麻醉科,内蒙古包头 014040

糖尿病 认知功能障碍 右美托咪定 PI3K-Akt信号通路

包头市卫生健康科技计划项目

2024wsjkkj104

2024

内蒙古医学杂志
内蒙古自治区医学会

内蒙古医学杂志

影响因子:0.537
ISSN:1004-0951
年,卷(期):2024.56(9)