Pdx-1、Ngn3联合MafA诱导干细胞分化为胰岛素分泌细胞移植治疗1型糖尿病大鼠的效果  

Effect of Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells Via Transfection of Pdx-1,Ngn3 and MafA on Treatment of Type 1 Diabetic Rats

作　　者：闫淑芳 袁慧娟[2] YAN Shufang;YUAN Huijuan(Department of Endocrinology,Huaihe Hospital of Henan University,Zhengzhou 475000,China;Department of Endocrinology,the People’s Hospital of Henan Province,Zhengzhou 450003,China)

机构地区：[1]河南大学淮河医院内分泌科,河南开封475000 [2]河南省人民医院内分泌科,河南郑州450003

出　　处：《河南医学研究》2024年第9期1553-1557,共5页Henan Medical Research

摘　　要：目的通过胰十二指肠同源盒1(Pdx-1)、神经元素3(Ngn3)联合V型肌腱膜纤维肉瘤癌基因同源基因A(MafA)共转染大鼠骨髓间充质干细胞(BMSCs)诱导分化为胰岛素分泌细胞(IPCs),移植治疗1型糖尿病大鼠并观察其疗效。方法Pdx-1、Ngn3和MafA共转染BMSCs诱导为IPCs,链脲佐菌素(STZ)制备45只1型糖尿病SD大鼠模型,BMSCs组(15只)肾被膜下移植2×10^(6) BMSCs,IPCs组(15只)大鼠肾被膜下移植2×10^(6) IPCs,sham-operation组(15只)大鼠肾被膜下注入等量生理盐水,另取15只健康SD大鼠肾被膜下注入等量生理盐水作为normal组。监测各组大鼠移植第0、7、14、21、28 d空腹血糖及体重;第21天对各组大鼠均行葡萄糖耐量试验;第28天取各组大鼠肾脏组织进行免疫组化。结果BMSCs和IPCs组大鼠血糖随时间下降,移植第21天两组大鼠空腹血糖低于移植第0天,且均低于同期sham-operation组(P<0.05),移植第28天IPCs组大鼠空腹血糖低于BMSCs组(P<0.05)。糖尿病大鼠中IPCs组和BMSCs组腹腔葡萄糖耐量实验曲线下面积小于sham-operation组,且IPCs组曲线下面积最小(P<0.05)。BMSCs组和IPCs组大鼠肾脏组织可见棕色荧光的胰岛素表达,且IPCs组胰岛素荧光光密度高于BMSCs组(P<0.05)。结论Pdx-1-Ngn3联合MafA诱导BMSCs形成的IPCs移植后在糖尿病大鼠体内可降低糖尿病大鼠的空腹血糖。Objective Pancreatic duodenal homeobox 1(Pdx-1),neurogenin(Ngn3)and V-type tendon fibrosarcoma oncogene homolog A(MafA)co-transfected bone marrow mesenchymal stem cells(BMSCs)into insulin-producing cells(IPCs),transplanted to treat type 1 diabetic rats and observe its effect.Methods Pdx-1,Ngn3 and MafA trans-differentiation BMSCs into IPCs.There were 45 SD rat models of type 1 diabetes were prepared by Streptozotocin(STZ),then divided into BMSCs group(15 cases):subrenal capsule transplantation 2×10^(6) BMSCs.IPCs group(15 cases):subrenal capsule transplantation 2×10^(6) IPCs.Sham-operation group(15 cases):subrenal capsule transplantation equal saline.There were 15 healthy SD rats were taken as normal group:an equal amount of saline was injected subrenal capsule.Fast blood glucose and body weight were monitored at 0,7,14,21,and 28 days after transplantation of rats in each group.Peritoneal glucose tolerance test was performed on rats in each group after transplantation 21 day.Kidney tissues of each group were taken for immunohistochemistry after transplantation 28 day.Results The blood glucose levels of rats in the BMSCs and IPCs groups decreased over time.On day 21 of transplantation,the fasting blood glucose levels of rats in both groups were significantly lower than those on day 0 of transplantation,and both were lower than those in the sham-operation group during the same period(P<0.05).On day 28 of transplantation,the fasting blood glucose levels of rats in the IPCs group were lower than those in the BMSCs group(P<0.05).In diabetes rats,the area under the curve of intraperitoneal glucose tolerance test in IPCs group and BMSCs group was smaller than that in sham-operation group,and the area under the curve in IPCs group was the smallest(P<0.05).Brown fluorescent insulin expression was observed in the renal tissue of rats in the BMSCs and IPCs groups,and the insulin fluorescence optical density in the IPCs group was higher than that in the BMSCs group(P<0.05).Conclusion IPCS trans-differentiation from BMSCs b

关 键 词：胰十二指肠同源盒1 神经元素3 V型肌腱膜纤维肉瘤癌基因同源基因A 大鼠骨髓间充质干细胞 胰岛素分泌细胞 1型糖尿病 

分 类 号：R587[医药卫生—内分泌]