沙格列汀对2型糖尿病模型小鼠肾组织单核细胞趋化蛋白1表达的影响  

Effects of saxagliptin on expression of renal tissue monocyte chemotactic protein-1 in mice model of type 2 diabetes mellitus

作　　者：薛竞帆 张启伦 毕双杰 温文杰 周婉 王炜 叶山东[1,2] XUE Jing-fan;ZHANG Qi-lun;BI Shuang-jie;WEN Wen-jie;ZHOU Wan;WANG Wei;YE Shan-dong(Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei ANHUI 230022,China;Department of Endocrinology,the First Affiliated Hospital of USTC,Hefei ANHUI 230001,China)

机构地区：[1]中国科学技术大学生命科学与医学部,安徽合肥230022 [2]中国科学技术大学附属第一医院内分泌科,安徽合肥230001

出　　处：《中国新药与临床杂志》2022年第2期104-109,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：安徽省中央引导地方科技发展专项(2017070802D147);国家自然科学基金(81800713)。

摘　　要：目的观察沙格列汀对2型糖尿病(T2DM)模型小鼠肾脏的保护作用及其对肾组织单核细胞趋化蛋白(MCP)-1表达的影响。方法将38只8周龄C57BL/6J小鼠分为正常对照组(n=8,常规饲料喂养)和高脂喂养组(n=30)。连续饲养4个月后,给予高脂喂养组小鼠链脲佐菌素(STZ)45 mg·kg^(-1)·d^(-1)腹腔注射,共3 d。选取造模成功小鼠24只,随机分成模型组、格列本脲组和沙格列汀组,每组8只,每日分别灌胃给予无菌生理盐水、格列本脲(2.5 mg·kg^(-1))和沙格列汀(5 mg·kg^(-1))。8周后称重,检测尿白蛋白(ALB)、视黄醇结合蛋白(RBP)、足细胞标志蛋白(PCX)、MCP-1和空腹血糖(FBG)、糖化血红蛋白(HbA_(1c))水平和肾组织MCP-1蛋白及m RNA表达情况,并观察肾组织病理学改变。结果与正常对照组比较,模型组小鼠体重降低,FBG、HbA_(1c)和尿ALB、RBP、PCX和MCP-1水平均升高,肾组织MCP-1蛋白和mRNA表达水平升高,差异均有显著意义(P<0.05),且模型组小鼠肾脏病理损伤及炎症明显加重。与模型组比较,格列本脲组、沙格列汀组小鼠体重升高,FBG、HbA_(1c)和尿ALB、RBP和MCP-1降低,肾组织MCP-1蛋白和m RNA表达水平降低,均差异显著(P<0.05),沙格列汀组尿PCX也显著降低(P<0.05),且沙格列汀组尿ALB、RBP、PCX、MCP-1以及肾组织MCP-1蛋白和m RNA水平低于格列本脲组(P<0.05),肾脏病理损伤及炎症明显减轻,小鼠体重、FBG和HbA_(1c)组间比较无显著差异(P>0.05)。结论沙格列汀可减轻T2DM小鼠肾脏损伤,这可能与其下调肾组织MCP-1的表达有关。AIM To observe the protective effect of saxagliptin on the kidney of type 2 diabetes mellitus(T2DM)mice and its effect on the expression of monocyte chemotactic protein(MCP)-1 in renal tissue.METHODS Thirty-eight8-weeks old SPF C57BL/6J mice were divided into normal control group(n=8,conventional feed)and high-fat feeding group(n=30).After continuous feeding for 4 months,mice in the high-fat feeding group were intraperitoneally injected with streptozotocin(STZ)45 mg·kg^(-1)·d^(-1) for consecutive 3 days.Twenty-four successful modeled mice were randomly divided into model group,glibenclamide group and saxagliptin group,with 8 mice in each group,and were given sterile normal saline,glibenclamide(2.5 mg·kg^(-1))and saxagliptin(5 mg·kg^(-1))by intragastric administration every day,respectively.After8 weeks of intragastrical administration,bodyweight,the albumin(ALB),retinol binding protein(RBP),podocalyxin(PCX),MCP-1 in urine,fasting blood-glucose(FBG)and glycosylated hemoglobin(HbA_(1c)),and the protein and m RNAexpression level of MCP-1 in renal tissue were detected.Besides,the histopathological changes of kidney were observed.RESULTS Compared with the normal control group,the bodyweight of mice in the model group was decreased,the levels of FBG,HbA_(1c),urinary ALB,RBP,PCX and MCP-1 were increased,and the protein and m RNA expression levels of MCP-1 in renal tissues were increased,with significant differences(P<0.05).In addition,the pathological damage and inflammation of kidney in the model group were significantly aggravated.Compared with the model group,the bodyweight of mice in the glibenclamide group and saxagliptin group was increased,FBG,HbA_(1c),urinary ALB,RBP and MCP-1 were decreased,the protein and m RNA expression levels of MCP-1 in renal tissues were decreased,with significant differences(P<0.05),and urinary PCX was also significantly decreased in the saxagliptin group(P<0.05).Besides,the urinary ALB,RBP,PCX and MCP-1 excretion levels and the protein and m RNA expression levels of MCP-1 in renal t

关 键 词：糖尿病 肾疾病 沙格列汀 单核细胞趋化蛋白1 

分 类 号：R977[医药卫生—药品]