右美托咪定通过调控PPARγ/NF-κB通路改善糖尿病脑损伤的机制探讨  

Exploration on the mechanism of dexmedetomidine alleviating diabetic brain injury by regulating PPARγ/NF-κB pathway

作　　者：马文俊 陈燕桦[1] 谢玉波[1] 梁东科[1] 冷志伟 黎杏梅 Ma Wenjun;Chen Yanhua;Xie Yubo;Liang Dongke;Leng Zhiwei;Li Xingmei(The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院,南宁530021

出　　处：《广西医科大学学报》2023年第5期807-813,共7页Journal of Guangxi Medical University

基　　金：国家自然科学基金面上项目(No.81373498);广西自然科学基金面上项目(No.2018GXNSFAA294007);广西壮族自治区卫生健康委员会自筹经费科研课题(No.Z-A20220403,No.Z2016317)。

摘　　要：目的:研究右美托咪定(DEX)对2型糖尿病大鼠脑损伤的影响及其机制。方法:选择48只SPF级雄性SD大鼠随机分为3组:正常组(control组)、糖尿病组(DM组)、DEX组,每组各16只;除control组外,其余组28只SD大鼠以高脂饲料喂养4周后以40 mg/kg单次腹腔注射链脲佐菌素(STZ)制备2型糖尿病模型;4周后检测随机血糖≥16.7 mmol/L为造模成功;DEX组在DM组造模成功后腹腔注射40μg/kg DEX,每日1次,连续注射2周,DM组给予等量的0.9%生理盐水腹腔注射,观察并记录各组大鼠空腹血糖、体重及生存情况;造模结束后处死大鼠,收集大脑皮层和海马组织,通过苏木精—伊红(HE)法检测大鼠脑组织病理学损伤变化,采用蛋白质免疫印迹(western blotting)和免疫组化法检测p-PPARγ、NF-κB的表达。结果:与control组相比,DM组大鼠的血糖升高、体重降低,可见一定程度的脑组织结构破坏及炎性细胞浸润。除此之外,p-PPARγ蛋白的表达量下降(P<0.05),NF-κB表达升高(P<0.05)。而在给予DEX处理后逆转了以上的变化,与DM组相比,DEX组的血糖下降、脑组织损伤较前改善,p-PPARγ蛋白的表达增加,NF-κB蛋白表达减少(均P<0.05)。结论:DEX可能通过调控PPARγ/NF-κB信号通路减轻2型糖尿病大鼠脑损伤。Objective:To investigate the effect and mechanism of dexmedetomidine(DEX)on brain injury in type 2 diabetic rats.Methods:48 SPF male SD rats were randomly divided into 3 groups:normal group(control group),diabetes mellitus group(DM group)and DEX group,with 16 rats in each group.Except for the control group,28 SD rats in the other groups were fed with high-fat diet for 4 weeks and then streptozotocin(STZ)was injected intraperitoneally at a single dose of 40 mg/kg to establish type 2 diabetes mellitus model.Random blood glucose≥16.7 mmol/L was defined as successful modeling after 4 weeks.The rats in the DEX group were intraperitoneally injected with 40μg/kg DEX once a day for 2 weeks after the DM model was successfully established,while the rats in the DM group were intraperitoneally injected with the same amount of 0.9%normal saline.Fasting blood glucose,body weight,and survival rate of rats in each group were observed and recorded.After the modeling was completed,the rats were sacrificed,and the brain cortex and hippocampal tissues were collected.Hematoxylin and eosin(HE)staining was used to detect histopathological changes in rat brain tissue.Western blotting and immunohistochemistry were used to detect the expressions of p-PPARγand NF-κB.Results:Compared with the control group,the rats in the DM group showed increased blood glucose and decreased body weight,and some degree of structural destruction of brain tissue and inflammatory cell infiltration were observed.In addition,the expression of p-PPARγprotein decreased(P<0.05),and NF-κB expression increased(P<0.05).However,the above changes were reversed after the administration of DEX treatment.Compared with the DM group,the DEX group showed decreased blood glucose,alleviated brain tissue injury,increased P-PPARγprotein expression and decreased NF-κB protein expression(all P<0.05).Conclusion:DEX may alleviate brain injury in type 2 diabetic rats by regulating the PPARγ/NF-κB signaling pathway.

关 键 词：右美托咪定 糖尿病 脑损伤 PPARΓ NF-ΚB 

分 类 号：R587.1[医药卫生—内分泌]