返回 
加入收藏
基于SIRT1/Akt/GSK3β/β-catenin信号通路研究右美托咪定对脓毒症模型大鼠脑损伤的保护机制
x
请在关注微信后，向客服人员索取文件
| 篇名： | 基于SIRT1/Akt/GSK3β/β-catenin信号通路研究右美托咪定对脓毒症模型大鼠脑损伤的保护机制 |
| TITLE： | Study on Protective Mechanism of Dexmedetomidine on Cerebral Injury in Sepsis Model Rats Based on SIRT 1/ Akt/GSK3β/β-catenin Signaling Pathway |
| 摘要： | 目的：通过右美托咪定（Dex）对脓毒症模型大鼠脑损伤中沉默信息调节因子1（SIRT1）/蛋白激酶B（Akt）/糖原合酶激酶3β（GSK3β）/β-连环蛋白（β-catenin）信号通路的影响，探究其对脑损伤的保护作用机制。方法：选取雄性SD大鼠80只，随机分为假手术组（Sham组）、脓毒症组（CLP组）、CLP+Dex组（10μg/kgDex）、CLP+Dex+Sirtinol组（10μg/kgDex+2μL/100gSIRT1抑制剂Sirtinol），每组20只。造模前2h，CLP+Dex+Sirtinol组大鼠经侧脑室注射给予Sirtinol；各组大鼠采用盲肠结扎穿孔法制备脓毒症模型（Sham组仅手术但不结扎穿孔）。造模结束后0、3、6h，CLP+Dex组、CLP+Dex+Sirtinol组大鼠分别腹腔注射Dex（10μg/kg），Sham组和CLP组大鼠腹腔注射等体积生理盐水。末次给药24h后，检测大鼠脑组织含水量、伊文思蓝（EB）含量、大脑皮层组织细胞凋亡情况和脑组织中白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）表达水平，以及海马组织中SIRT1、p-Akt、p-GSK3β、β-catenin蛋白表达水平。结果：与Sham组比较，CLP组大鼠脑组织含水量、EB含量、大脑皮层组织凋亡细胞数及脑组织中IL-1β、TNF-α表达水平显著增加或升高（P＜0.05）；海马组织SIRT1、p-Akt、p-GSK3β、β-catenin蛋白表达水平显著降低（P＜0.05）。与CLP组比较，CLP+Dex组大鼠脑组织含水量、EB含量、大脑皮层组织凋亡细胞数及脑组织中IL-1β、TNF-α表达水平显著减少或降低（P＜0.05）；海马组织中SIRT1、p-Akt、p-GSK3β、β-catenin蛋白表达水平均显著升高（P＜0.05）。而Sirtinol可显著逆转Dex的上述脑保护和因子调节作用（P＜0.05）。结论：Dex对脓毒症模型大鼠具有脑保护作用，该作用可能是通过激活SIRT1/Akt/GSK3β/β-catenin信号通路而发挥抗炎、抗凋亡等作用，从而减轻脑水肿、保护血脑屏障并减轻脑损伤。 |
| ABSTRACT： | OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury. |
| 期刊： | 2020年第31卷第21期 |
| 作者： | 董晓柳，宋丽华，董伟，高铭，张秀清，刘蔚然，徐士军，刘铁军，崔璐莎 |
| AUTHORS： | DONG Xiaoliu， SONG Lihua，DONG Wei，GAO Ming，ZHANG Xiuqing，LIU Weiran，XU Shijun，LIU Tiejun，CUI Lusha |
| 关键字： | 右美托咪定；脓毒症；脑损伤；脑保护作用；SIRT1/Akt/GSK3β/β-catenin信号通路；炎症反应；机制；大鼠 |
| KEYWORDS： | Dexmedetomidine； Sepsis； Cerebral injury ； Brain protection effect ； SIRT1/Akt/GSK3 β/β-catenin signaling |
| 阅读数： | 412 次 |
| 本月下载数： | 5 次 |
* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！
