脐带间充质干细胞不同模式干预对2型糖尿病大鼠胰岛细胞凋亡的作用比较  

Effects of umbilical cord mesenchymal stem cell on islet cell apoptosis of diabetes mellitus rats:a comparision of multiple doses and single dose

作　　者：陈频[1] 黄山[2] 徐向进[1] 黄梁浒[1] 邵珠林 温代芬 

机构地区：[1]南京军区福州总医院内分泌科,福州350025 [2]福建医科大学分子生物学系,福州350005

出　　处：《中华细胞与干细胞杂志（电子版）》2016年第1期36-41,共6页Chinese Journal of Cell and Stem Cell（Electronic Edition）

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)

摘　　要：目的对比脐带间充质干细胞(UCMSC)不同模式干预对2型糖尿病(T2DM)大鼠胰岛细胞凋亡的作用及其与TLR4/NF-κB炎症通路的关系。方法将SD大鼠分为正常对照组(NC组)、T2DM组、UCMSC A组和UCMSC B组,每组8只,予相应干预8周:UCMSC以尾静脉输注方式干预,其中UCMSC A组采用单次大量模式(细胞数20×106个);UCMSC B组采用多次足量序贯模式(每次细胞数5×106个,每两周干预1次共4次)。定期检测各组大鼠空腹血糖(FBG)、胰岛素(INS)、C肽(C-P);观察胰腺组织形态变化;TUNEL法检测胰岛细胞凋亡;Western blot法检测胰腺组织TLR4、NF-κB及IL-6蛋白表达水平。组间比较采用单因素方差分析。结果治疗8周末,与T2DM组比较,UCMSC A组和UCMSC B组大鼠FBG均呈明显下降,其中UCMSC B组明显低于UCMSC A组[(20.0±3.5)比(13.1±1.7)、(7.2±2.2)],P<0.05;与T2DM组比较,两个治疗组大鼠INS和C-P水平呈不同程度增高;T2DM组大鼠胰腺组织形态紊乱,仅见少量胰岛细胞团存在,而两个治疗组大鼠胰腺组织形态呈不同程度改善;与T2DM组比较,两个治疗组大鼠胰岛细胞凋亡指数明显降低,以UCMSC B组为甚;与T2DM组比较,两个治疗组大鼠胰腺组织TLR4、NF-κB及IL-6蛋白表达降低,以UCMSC B组为甚,分别为(1.58±0.43)比(1.15±0.27)、(0.96±0.20),(1.06±0.22)比(0.80±0.15)、(0.62±0.10),(0.91±0.10)比(0.77±0.09)、(0.60±0.16),均P<0.05。结论多次足量序贯输注干预模式对2型糖尿病大鼠糖代谢和胰岛分泌功能具有较好的改善作用,其机制可能与其下调TLR4/NF-κB炎症通路抑制胰岛β细胞凋亡相关。Objective To compare the effects of different umbilical cord mesenchymal stem cell（UCMSC）intervenings on the islet cell apoptosis of type 2 diabetes mellitus（T2DM）rats and the role of the TLR4/NF-κB inflammatory pathway. Method SD rats were randomly divided into four NC, T2 DM, UCMSC A and UCMSC B groups（n = 8）. Rats of each group were given the appropriate therapy for 8 weeks respectively. The rats of UCMSC A were given by tail vein injection with 20 × 10~6 cells once while UCMSC B were given with 5 × 10~6 cells once every two week for four times. During the treatment period, the serum fasting blood glucose（FBG）, insulin（INS） and peptide C（C-P） were monitored. The changes of pancreatic tissue pathology were observed. The apoptosis status of the islet cells were evaluated through TUNEL. And the expressions of the TLR4, NF-κB and IL-6 protein in pancreas were determined by Western blot. Mean data between groups was compared with one-way ANOVA. Result After 8-week treatment, compared with T2 DM group, the FBG of both intervening groups were significantly decreased, and it was lowest in the UCMSC B group.[（20.0 ± 3.5）vs（13.1 ± 1.7）,（7.2 ± 2.2）, P〈0.05]. While The INS and C-P were increased in both intervening groups. The islet architecture was impooved and cell unite numbers were significantly increased in the two treatment groups. The same trend in islet cell apoptosis by TUNEL could be observed. The expressions of the TLR4, NF-κB and IL-6 protein in pancreas tissue were significantly reduced in the two treatment groups. And the above indexes in UCMSC A were significantly ameliorated compared to those in the UCMSC B group[（1.58 ± 0.43）vs（1.15± 0.27）,（0.96 ± 0.20）;（1.06 ± 0.22）vs（0.80 ± 0.15）,（0.62 ± 0.10）;（0.91 ± 0.10）vs（0.77± 0.09）,（0.60 ± 0.16）,P〈0.05 for all]. Conclusions Repeated administration of UCMSC is superior to single administration in improving the glucose metabolish and islet β cell function on type 2 diabetic

关 键 词：糖尿病 2型 脐带 间充质干细胞 胰岛 细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]