摘要
目的探讨胰高血糖素样肽I（GLP．1）受体激动剂利拉鲁肽（LIRA）或脐带间充质干细胞（UC．MSCs）单用及联用对2型糖尿病（T2DM）SD大鼠糖代谢及胰岛分泌功能的作用及其与胃肠激素相关性。方法以高糖高脂喂养及链脲佐菌素（STZ）腹腔注射制备SD大鼠T2DM模型，将40只成模大鼠随机分为4组：T2DM组、T2DM＋UC．MSCs组、T2DM＋LIRA组、T2DM＋LIRA＋UC．MSCs组；每组均为10只。分别给予相应干预治疗，共8周，其中利拉鲁肽按200μg/kg，每日皮下注射2次；UC．MSCs以尾静脉注射细胞5×10个。定期检测各组大鼠一般状况、糖化血红蛋白（HbA1c）；ELISA法检测血清C肽（C-P）、胰高血糖素（Glu）、GLP-1、胃泌素（GAS）及胆囊收缩素（CCK）。组间均数比较采用单因素方差分析。结果治疗8周后，与T2DM组比较，T2DM＋UC—MSCs、T2DM＋LIRA和T2DM＋LIRA＋UC—MSCs组大鼠HbA1c均呈明显降低[（9．1±0．4）％比（7．2±O．4）%、（3．9±0．3）％、（3．1±0．3）％，F=815．220，P〈0．05]；且T2DM＋LIRA＋UC．MSCs组HbA1c低于T2DM＋UC—MSCs组和T2DM＋LIRA组t=-28．105、-5．918，P〈0．05）。与T2DM组比较，T2DM＋UC—MSCs组C—P明显增加（t=8．774，P〈0．051，而Glu、GLP-1、GAS及CCK差异无统计学意义（t=2．168、1．894、1．768、1．516，P〉O．05）；T2DM＋LIRA组和T2DM＋LIRA＋UC．MSCs组C-P、GLP-1、GAS和CCK水平均明显升高（t=-18．115～35．732，均P〈0．05），Glu降低（￡=3．022、11.859，均P〈0．051；与T2DM＋LIRA组比较，T2DM＋LIRA＋uc．MSCs组C-P、GLP-1、GAS和CCK明显升高（t=9．107、7．635、9．870、19．152，均P〈0．05），Glu降低t=-13．976，P〈0．05）。Pearson双变量分析发现，大鼠空腹血清C-P与GLP-1、GAS及CCK呈正相关（r=0．401、0．628、0．619，均P〈0．01），与Glu呈负相关（r=-0．603，P〈0．01）。大鼠空腹血清Glu水平与GLP-1、GAS及CCK呈负相关
Objective To observe the efficacy of glucagon like peptide-1（GLP-1） receptor agonist liraglutide（LIRA） combined with umbilical cord mesenchymal stem cells（UC-MSCs） on the glucose metabolism and islet 13 cell function in type 2 diabetic SD rats. Methods Type 2 diabetic SD rats models were established by giving high-carbonhydrate-fat diet and then intraperitoneal injecting of streptozotocin. The rats models were randomly divided into four groups according the table of random number： type 2 diabetes mellitus（T2DM）, T2DM＋UC-MSC, T2DM＋LIRA, T2DM＋LIRA＋UC-MSCs, 10 rats in each group. Rats of each group were given the appropriate drug therapy for 8 weeks respectively. Liraglutide was given by subcutaneous injection with 200 μg/kg dosage. UC-MSCs were given by tail vein injection with 5 × 106 ceils. During the treatment period, the general condition indexs of each group were monitored. The serum glycated hemoglobin A1c（HbA1c）, peptide C（C-P）, glucagon（Glu）, GLP-1, gastrin（GAS） and cholecystokinin （CCK） were measured respectively. Mean data between groups was compared with one-way ANOVA. Results After 8-week of treatment, compared with T2DM group, HbA1c of the T2DM ＋ UC-MSCs, T2DM＋LIRA and T2DM＋LIRA＋UC-MSCs group decreased significantly（（9.1±0.4）% vs （7.2±0.4）%, （3.9±0.3）%, （3.1±0.3）%, respectively, F=815.220, P〈0.05）, and it was lowest in T2DM＋LIRA＋UC-MSCs group （t=-28.105, -5.918, both P〈0.05）. Compared with T2DM group, the C-P of T2DM＋UC-MSC group increased significantly（t=8.774, P〈0.05）, while there were no much changes in Glu, GLP-1, GAS and CCK（t=2.168, 1.894, 1.768, 1.516, all P〉0.05）; but the C-P, GLP-1, GAS and CCK in T2DM＋LIRA group and T2DM＋ LIRA ＋ UC-MSCs group increased markably（t=-18.115- 35.732, all P〈0.05）, while the Glu decreased remarkably （t=3.022, 11.859, both P〈0.05）. Compared with T2DM＋LIRA group, the C-P, GLP-1, GAS and CCK in T2DM＋LIRA＋UC-MSCs group also increased signifi
出处
《中华糖尿病杂志》
CAS
CSCD
2015年第12期735-740,共6页
CHINESE JOURNAL OF DIABETES MELLITUS
基金
福建省自然科学基金面上项目（2012J01403）
全军医学科学技术研究“十二五”计划（CWSIIJ254）
关键词
糖尿病
2型
胰高血糖素样肽1受体激动剂
脐带间充质干细胞
胰岛B细胞功能
胃肠激素
Diabetes mellitus, type 2
cord mesenchymal stem cells
Islet β cell function
Glucagon like peptide-1 receptor agonist
Umbilical Gastrointestinal hormone
