CAJ | 학술논문

目的探讨利拉鲁肽(liraglutide)与骨髓间充质干细胞(bone marrow mesenchymal stem cells,BM-MSCs)联合治疗对1型糖尿病(T1DM)大鼠模型糖代谢的影响.方法以60 mg/kg剂量腹腔注射链脲佐菌素制备T1 DM大鼠模型,随后按随机数字表法分为(1)T1DM组(n=10)、(2)BM-MSCs治疗组(n=10)、(3)利拉鲁肽治疗组(LIRA,n=10)、(4)利拉鲁肽联合BM-MSCs治疗组(LIRA+BM-MSCs,n=10),给予相应干预8周.测定各组大鼠随机血糖、HbA1C、24 h尿量和24 h尿蛋白;采用ELISA法检测血清胰岛素、C肽、胰升糖素、胃泌素、胆囊收缩素和胰升糖素样肽l(GLP-1)等激素水平;免疫组化测定胰腺组织中胰岛素和胰升糖素的表达.结果 8周后,LIRA+BM-MSCs组大鼠血糖、HbA1C、24 h尿量和24h尿蛋白较其他3组均明显降低(P＜0.05);分别与T1DM组和BM-MSCs组比较,LIRA+BM-MSCs组血清胰岛素、C肽、胃泌素、胆囊收缩素和GLP-1水平均明显升高,胰升糖素水平降低(均P＜0.05);与LIRA组比较,LIRA+BM-MSCs组血清胰岛素、C肽、胃泌素和胆囊收缩素水平均明显升高(P＜0.05),胰升糖素和GLP-1水平无差异(P＞0.05);相关分析发现,血清胰岛素水平分别与胃泌素(r=0.544,P＜0.01)、胆囊收缩素(r=0.710,P＜0.01)和GLP-1 (r=0.669,P＜0.01)水平呈正相关,与胰升糖素水平呈负相关(r=-0.506,P＜0.01),胰升糖素与胃泌素(r=-0.364,P＜0.05)、胆囊收缩素(r=-0.433,P＜0.01)和GLP-1(r=-0.591,P＜0.01)呈负相关;免疫组化显示,LIRA+BM-MSCs组大鼠胰腺组织胰岛素的阳性面积比例较其他3组均明显升高,胰升糖素比例降低(均P＜0.05).结论利拉鲁肽联合骨髓间充质干细胞可能比两者单独治疗能够更好地介导胃肠激素分泌而改善T1DM大鼠的糖代谢.
목적 탐토리랍로태(liraglutide)여골수간충질간세포(bone marrow mesenchymal stem cells,BM-MSCs)연합치료대1형당뇨병(T1DM)대서모형당대사적영향.방법 이60 mg/kg제량복강주사련뇨좌균소제비T1 DM대서모형,수후안수궤수자표법분위(1)T1DM조(n=10)、(2)BM-MSCs치료조(n=10)、(3)리랍로태치료조(LIRA,n=10)、(4)리랍로태연합BM-MSCs치료조(LIRA+BM-MSCs,n=10),급여상응간예8주.측정각조대서수궤혈당、HbA1C、24 h뇨량화24 h뇨단백;채용ELISA법검측혈청이도소、C태、이승당소、위비소、담낭수축소화이승당소양태l(GLP-1)등격소수평;면역조화측정이선조직중이도소화이승당소적표체.결과 8주후,LIRA+BM-MSCs조대서혈당、HbA1C、24 h뇨량화24h뇨단백교기타3조균명현강저(P＜0.05);분별여T1DM조화BM-MSCs조비교,LIRA+BM-MSCs조혈청이도소、C태、위비소、담낭수축소화GLP-1수평균명현승고,이승당소수평강저(균P＜0.05);여LIRA조비교,LIRA+BM-MSCs조혈청이도소、C태、위비소화담낭수축소수평균명현승고(P＜0.05),이승당소화GLP-1수평무차이(P＞0.05);상관분석발현,혈청이도소수평분별여위비소(r=0.544,P＜0.01)、담낭수축소(r=0.710,P＜0.01)화GLP-1 (r=0.669,P＜0.01)수평정정상관,여이승당소수평정부상관(r=-0.506,P＜0.01),이승당소여위비소(r=-0.364,P＜0.05)、담낭수축소(r=-0.433,P＜0.01)화GLP-1(r=-0.591,P＜0.01)정부상관;면역조화현시,LIRA+BM-MSCs조대서이선조직이도소적양성면적비례교기타3조균명현승고,이승당소비례강저(균P＜0.05).결론 리랍로태연합골수간충질간세포가능비량자단독치료능구경호지개도위장격소분비이개선T1DM대서적당대사.
Objective To investigate the effect of liraglutide combined with bone marrow mesenchymal stem cells (BM-MSCs) on glucose metabolism in experimental type 1 diabetic (T1DM) rats.Methods T1 DM rats were established by injecting 60 mg/kg streptozotocin.According to random number table,they were divided into T1DM group (n =10),BM-MSCs group (n =10),LIRA group (n =10),and LIRA+BM-MSCs group (n =10),and were treated for 8 weeks respectively.Random blood glucose,24 h urine volume and protein excretion were tested.Serum concentrations of insulin,C-peptide,glucagon,gastrin,cholecystokinin,and glucagon-like peptid 1 (GLP-1) were assayed by ELISA.Expressions of insulin and glucagon in pancreas were measured by immunohistochemistry.Results After 8 weeks,the levels of random blood glucose,HbA1C,24 h urine volume and 24 h urinary protein excretion in group 4 were significantly decreased compared to the other three groups (P＜0.05).Compared to T1DM group and BM-MSCs group,the levels of insulin,C-peptide,gastrin,cholecystokinin and GLP-1 in LIRA+BM-MSCs group were significantly increased,while glucagon was decreased (P＜0.05).Compared to group LIRA,the levels of insulin,C-peptide,gastrin,and cholecystokinin in LIRA + BM-MSCs group were increased (P ＜ 0.05),there was no significantly difference in glucagon or GLP-1 (P＞0.05).The analysis revealed that the level of insulin was positively correlated with gastrin (r =0.544,P＜0.01),cholecystokinin (r =0.710,P＜0.01) and GLP-1 (r =0.669,P＜ 0.01),but was negatively correlated with glucagon (r =-0.506,P＜0.01);the level of glucagon was negatively correlated with gastrin (r =-0.364,P＜0.05),cholecystokinin (r =-0.433,P＜0.01) and GLP-1 (r =-0.591,P＜ 0.01).Compared to the other three groups respectively,immunohistochemistry displayed that the positive area of insulin in pancreas was significantly increased in LIRA + BM-MSCs group,while that of glucagon was decreased (P＜ 0.05).Conclusions By means of regulating gastrointestinal hormones efficiently,combination of liraglutide withBM-MSCs may improve glucose metabolism more efficaciously than treatment with a single agent in T1DM rats.