机构地区:[1]电子科技大学附属医院,四川省人民医院细胞移植中心,成都610072 [2]遵义医学院临床医学院
出 处:《中华糖尿病杂志》2018年第3期226-233,共8页CHINESE JOURNAL OF DIABETES MELLITUS
基 金:国家重点研究发展计划项目(973计划)(2015CB964703);四川省科研院所科技成果转化项目(14010127);四川省科技厅应用基础计划项目(2016JY0020)
摘 要:目的探讨Sprague-Dawley(SD)大鼠胰岛与骨髓间充质干细胞(BMSCs)联合移植能否提高治疗糖尿病的远期疗效。 方法体外实验:选健康1周龄SD大鼠4只,分离培养BMSCs,另选健康6~8周龄SD大鼠3只,分离胰岛细胞,将两种细胞分为1640培养基组、BMSCs培养组、胰岛培养组、胰岛与BMSCs联合培养组共4组进行体外细胞培养(所有培养组的培养基均为1640培养基)。各组于培养后的第1、3、7天分别进行细胞形态学观察及胰岛素及C肽水平测定。体内实验:选取体重180~200 g的健康雄性SD大鼠,采用1%链脲佐菌素-柠檬酸盐缓冲液60 mg/kg腹腔注射方法制备1型糖尿病模型。将成模糖尿病大鼠随机分为模型组、BMSCs移植组、胰岛移植组、胰岛与BMSCs移植组(联合移植组)共4组(每组15只)进行体内细胞移植实验。各组于移植后的第1、3、7、14、30天分别检测大鼠的空腹血糖及体重、胰岛素、C肽水平、总胆红素及谷草转氨酶和谷丙转氨酶水平。多组间数据比较采用单因素方差分析,两组间比较采用t检验。 结果与胰岛移植组比较,联合移植组血糖水平降低(t=11.44~28.02,均P〈0.05)、胰岛素(t=10.03~6.86,均P〈0.05)及C肽分泌水平升高(t=1.47~2.59,均P〈0.05)、总胆红素(t=7.67~6.39,均P〈0.05)及谷草转氨酶(t=12.00~8.89,均P〈0.05)和谷丙转氨酶(t=8.08~10.40,均P〈0.05)水平降低、胰岛素的免疫荧光强度表达较亮,模型组与BMSCs移植组比较上述指标差异无统计学意义(均P〉0.05)。 结论胰岛与BMSCs联合移植与单独胰岛移植相比能更好地治疗1型糖尿病,对1型糖尿病可能具有远期疗效。ObjestiveTo explore the long-term therapeutic effects of co-transplantation of Sprague-Dawley (SD) rats islets and bone marrow mesenchymal stem cells (BMSCs) to treat type 1 diabetes mellitus (T1DM). MethodsBMSCs were isolated from 1 week of age of 4 healthy male SD rats while islets were isolated from 6-8 weeks of age of 3 healthy male SD rats BMSCs and islets were both cultured with 1640 nutrient medium in either separately or together in vitro. The cell morphology, levels of insulin and C-peptide in each group were examined at the 1st, 3rd, and 7th day after culture. T1DM model (male SD rats, body weight 180-200 g) was established by administration of 1% streptozotocin (STZ) citrate buffer (60 mg/kg) through intraperitoneal injection. T1DM model rats were randomly divided into 4 groups: model group, BMSCs transplantation group, islets transplantation group, and co-transplantation group (15 rats each group) for the cell transplantation test in vivo. The fasting glucose, body weight, insulin, C-peptide, total bilirubin (TBIL), aspartate transaminase (AST) and alanine aminotransferase (ALT) of each group were examined at the 1st, 3rd, 7th, 14th, and 30th day after transplantation. Data between multigroups were analyzed by ANOVA, and data between two groups were analyzed by t test. ResultsCompared to islets transplantation group, blood glucose in co-transplantation group's was lower (t=11.44-28.02, P〈0.05), and insulin (t=10.03-6.86, P〈0.05) and C-peptide (t=1.47-2.59, P〈0.05). However, the TBIL (t=7.67-6.39, P〈0.05), AST (t=12.00-8.89, P〈0.05), and ALT (t=8.08-10.40, P〈0.05) in co-transplantation group were lower than those in islets transplantation group. The expression intensity of insulin was stronger in co-transplantation group than islets transplantation group. The differences of above indexes between model group and BMSCs group had no statistical significance (all P〉0.05). ConclusionCompared with islets transplant
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