摘要
目的骨髓间充质干细胞(BMSCs)移植入糖尿病模型鼠胰腺包膜下,观察BMSCs的分布及对糖尿病的治疗效果。方法利用绿色荧光蛋白(EGFP)标记雄性SD大鼠BMSCs,以多点注射的方法移植入糖尿病大鼠胰腺包膜下,血糖仪监测血糖,ELISA法检测胰岛素和C-肽水平。移植后8周,通过EGFP示踪植入的BMSCs的分布,取EGFP标记的胰腺组织,免疫荧光染色检测是否存在EGFP和胰岛素共表达,荧光原位杂交检测是否存在EGFP和PDX1共表达。结果胰腺包膜下移植BMSCs有效降低糖尿病鼠血糖,升高血清胰岛素和C-肽水平(P<0.05)。至移植后8周,植入细胞稳定表达绿色荧光蛋白,EGFP标记细胞分布于胰岛(12.46%)、血管(4.4%)、腺泡(9.24%)、导管(3.21%),或集中分布于局部(70.69%)。免疫组化发现EGFP和胰岛素共表达细胞(5.16%),荧光原位杂交发现EGFP和PDX1共表达细胞(0.96%)。结论BMSCs胰腺包膜下移植后在胰腺中发生再分布,在胰腺微环境中能够分化为胰岛素分泌细胞,有效逆转血糖、胰岛素和C-肽水平。
Objective To investigate the cell distrubution and the therapeutic outcome of BMSCs injection into subcapsular pancreas of diabetic rats model. Methods BMSCs of male SD rat were labeled with enhanced green fluorescent protein （EGFP）, administered them to diabetic rats by injecting into subcapsular pancreas at multiple points. Blood glucose levels, blood insulin levels and blood C-peptide levels were monitored. Distribution of BMSCs were monitored by EGFP detection 8 weeks after transplantation, EGFP and insulin double-positive cells were detected by immunofluorescence, EGFP and PDX1 double-positive cells were detected by fluorescence in situ hybridization （FISH）. Results Transplantation of BMSCs into pancreas reduced blood glucose, increased blood insulin and C-peptide in experimental diabetic rats was significantly differently from that of control group （P 〈 0. 05 ）. Up to 8 weeks after transplantation, cells of donor origin stabely expressed EGFP, and EGFP labled ceils were distributed in islets （ 12. 46% ） ,blood vessel（4. 4% ）, acinus（9. 24% ） and duct（3. 21% ）, the majority of EGFP labled cells were distributed in local focus （70. 69% ）. Immunofluorescence revealed double-positive cells of EGFP and insulin （5. 16% ）, FISH revealed double-positive cells of EGFP and PDX1 （0. 96% ）. Conclusion Transplantation of BMSCs into pancreas effectively reversed hyperglycemia of experimental diabetic rats, transplanted BMSCs redistributed in pancreas, and transplanted BMSCs differentiated into insulin-secreting cells within pancreatic microenvironment.
出处
《基础医学与临床》
CSCD
北大核心
2009年第6期584-588,共5页
Basic and Clinical Medicine
基金
国家973前期专项(2004CCA01500)
广东省自然科学基金(6027540)
关键词
骨髓间充质干细胞
糖尿病
胰腺
移植
胰岛素
分化
bone marrow mesenchymal stem cells
diabetes
pancreas
transplantation
insulin
differentiation
