脐带间充质干细胞联合利拉鲁肽对2型糖尿病大鼠模型胰腺炎症损伤的保护作用  

Protective effects of combining human umbilical cord mesenchymal stem cells and glucagon like peptide-1 receptor agonist on the islet inflammatory injury in rat model of type 2 diabetes mellitus

作　　者：陈频[1] 黄山[3] 温代芬 黄梁浒[2] 邵珠林 徐向进[1] 黄勤[4] Chen Pin Huang Shan Wen Daifen Huang Lianghu Shao Zhulin Xu Xiangjin Huang Qin(Department of Endocrinology, Fuzhou General Hospital of Nanfing Command, Fuzhou 350025, Chin)

机构地区：[1]南京军区福州总医院内分泌科,福州350025 [2]南京军区福州总医院干细胞中心,福州350025 [3]福建医科大学分子生物学教研组,福州350004 [4]长海医院内分泌科,上海200433

出　　处：《中华内分泌代谢杂志》2016年第12期1003-1009,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：全军医学科学技术研究“十二五”计划（CWSIIJ254）;福建省自然科学基金面上项目（2012J01403）

摘　　要：目的探讨脐带间充质干细胞联用利拉鲁肽对2型糖尿病SD大鼠胰岛功能的作用及其可能的机制。方法以高糖高脂/链脲佐菌素的方法制备2型糖尿病模型，随机分为4组：糖尿病对照组（T2DM组）、脐带间充质干细胞治疗组（T2DM＋UC-MSCs组）、利拉鲁肽治疗组（T2DM＋LIRA组）及利拉鲁肽和脐带间充质干细胞联合治疗组（T2DM＋LIRA＋UC-MSCs组）。每组10只，相应治疗8周。定期检测大鼠HbA1C、胰岛素、C肽、胰升糖素，免疫组织化学法检测胰岛素和胰升糖素表达，TUNEL法检测胰岛细胞凋亡及Western印迹检测胰腺组织核因子-κB（nuclear factor-κB, NF-κB）、Toll样受体4（Toll-like recpter 4, TLR4）蛋白表达。结果治疗8周末，与T2DM组比较，T2DM＋UC-MSCs组、T2DM＋LIRA组和T2DM＋LIRA＋UC-MSCs组大鼠HbA1C均明显降低，以T2DM＋LIRA＋UC-MSCs组降低最大[（9.1±0.4）%对（7.2±0.4）%、（3.9±0.3）%、（3.1±0.3）%, P〈0.05]；T2DM＋UC-MSCs组胰岛素和C肽增加，T2DM＋LIRA组和T2DM＋LIRA＋UC-MSCs组胰岛素和C肽升高且胰升糖素降低，并以T2DM＋LIRA＋UC-MSCs组改善最明显（P〈0.05）。胰腺组织胰岛素阳性面积占胰岛总面积百分比明显增高，而胰升糖素表达明显降低；胰岛细胞凋亡减轻（P〈0.05）。胰腺组织NF-κB和TLR4蛋白表达均有不同程度降低，分别为[（0.75±0.10）对（0.60±0.08）、（0.47±0.08）、（0.31±0.04），F＝37.175，P〈0.05]和[（1.24±0.12）对（0.93±0.10）、（0.95±0.09）、（0.74±0.07），F＝46.902，P〈0.05]，上述指标的改善以T2DM＋LIRA＋UC-MSCs组最明显（P〈0.05）。结论脐带间充质干细胞和利拉鲁肽联用对2型糖尿病SD大鼠胰岛功能的改善作用优于两者单用，其机制可能与其下调TLR4/NF-κB炎症信号通路相关。Objective To investigate the effects and mechanism of combining human umbilical cord mesenchymal stem cells and liraglutide on the islet function of type 2 diabetes mellitus SD rats. Method Type 2 diabetes mellitus rats were established by giving high carbonhydrate and fat diet for 4 weeks to SD rats, and then 30 mg/kg streptozotocin was injected intraperitoneally. Type 2 diabetes mellitus rats were randomly divided into four groups according the table of random number： Type 2 diabetes mellitus group （T2DM group）, umbilical cord mesenchymal stem cells treatment group （ T2DM ＋ UC-MSCs group ）, liraglutide treatment group （ T2DM ＋ LIRA group） and liraglutide combined umbilical cord mesenchymal stem ceils treatment group （T2DM ＋ LIRA＋UC-MSCs group）. Each group included 10 rats, and rats were given the appropriate drug therapy for 8 weeks. HbAic, insulin, C-peptide, and glucagon levels were measured. The expressions of insulin and glucagon in pancreas tissue were measured through immunohistochemistry analysis. The apoptosis status of the islet cells in pancreas tissue were evaluated through TUNEL. And the expressions of the nuclear factor-κB （NF-κB） and Toll-like recpter 4 （ TLR4 ） protein in pancreas tissue were determined by Western blot. Result After 8 weeks treatment, compared with T2DM group, HbAlc of T2DM ＋ UC-MSCs group, T2DM ＋ LIRA group and T2DM ＋ LIRA ＋ UC-MSCs group decreased significantly, and it was lowest in T2 D M ＋LIRA＋UC-MSCs group [ （ 9.1±0.4 ） % vs （ 7.2 ±0.4 ） %, （ 3.9± 0.3 ） %, （3.1±0.3 ）%, respectively, P〈0.05 ]. The insulin and C-peptide of T2DM ＋UC-MSC group were significantly increased （ P〈0.05 ）. The insulin and C-peptide were increased while the glucagon was significantly decreased in T2DM＋LIRA group and T2DM＋LIRA＋UC-MSCs group （P〈0.05）. The ratio of insulin positive area in pancreas tissue was obviously rised, while the ratio of glucagon positive area in pancreas tissue was clearly descended in T2DM

关 键 词：糖尿病 2型 利拉鲁肽 间充质干细胞 胰岛功能 TLR4/NF-κB通路 

分 类 号：R587.1[医药卫生—内分泌] R-332[医药卫生—内科学]