吡格列酮联合内皮祖细胞移植改善糖尿病肾功能

发布时间：2018-03-24 06:39

本文选题：内皮细胞　切入点：噻唑烷二酮类　出处：《中国组织工程研究》2017年17期

【摘要】：背景:研究表明,吡格列酮可促进内皮祖细胞增殖活化,抑制内皮祖细胞凋亡。作者推测,吡格列酮干预和内皮祖细胞移植联合治疗可能会更有效地缓解高血糖症状,修复糖尿病肾脏损伤。目的:观察吡格列酮联合内皮祖细胞移植对糖尿病大鼠肾功能的改善作用。方法:(1)体外复苏人内皮祖细胞并进行CM-Dil标记,移植前备用;(2)从75只Wistar大鼠中随机选15只不做任何处理作为正常对照组,余60只连续5 d腹腔注射40 mg/kg链脲佐菌素柠檬酸钠溶液建立1型糖尿病大鼠模型,造模4周后随机分为糖尿病组、吡格列酮组、内皮祖细胞移植组和联合治疗组,经尾静脉注射内皮祖细胞悬液和/或20 mg/kg吡格列酮灌胃,连续治疗4 d;(3)治疗8周后测定各组大鼠血糖、血清胰岛素、血肌酐、尿素氮及24 h尿蛋白水平,荧光显微镜观测CM-Dil标记的内皮祖细胞存活及分布情况,TUNEL法检测肾细胞凋亡情况,并计算肾质量/体质量比值。结果与结论:(1)与糖尿病组比较,内皮祖细胞组、吡格列酮组大鼠血糖、血肌酐、尿素氮及24 h尿蛋白水平明显降低,血清胰岛素明显升高,差异有显著性意义(P0.05),联合治疗组大鼠血糖、血肌酐、尿素氮及24 h尿蛋白水平降低更明显(P0.01),血清胰岛素升高更明显(P0.01);(2)内皮祖细胞组、吡格列酮组大鼠肾质量/体质量比值低于糖尿病组(P0.05),联合治疗组低于内皮祖细胞组、吡格列酮组(P0.05);(3)联合治疗组大鼠CM-Dil标记阳性细胞明显多于内皮祖细胞移植组;(4)正常对照组细胞凋亡数最少,糖尿病模型组细胞凋亡数最多,与糖尿病模型组比较,内皮祖细胞移植组和吡格列酮组凋亡细胞数明显减少,联合组进一步减少;(5)结果表明,吡格列酮联合内皮祖细胞移植能够有效降低大鼠血糖、肌酐、尿素氮及24 h尿蛋白水平,升高血清胰岛素水平,减少肾组织细胞凋亡,在一定程度上改善糖尿病大鼠肾功能紊乱。
[Abstract]:Background: studies have shown that pioglitazone can promote the proliferation and activation of endothelial progenitor cells and inhibit the apoptosis of endothelial progenitor cells. The authors speculate that the combination of pioglitazone and endothelial progenitor cell transplantation may relieve hyperglycemia more effectively. Objective: to observe the effect of pioglitazone combined with endothelial progenitor cell transplantation on renal function of diabetic rats. Before transplantation, 15 Wistar rats were randomly selected as normal control group. The remaining 60 rats were intraperitoneally injected with 40 mg/kg streptozotocin citrate solution for 5 days to establish the model of type 1 diabetes mellitus. After 4 weeks, the model was randomly divided into diabetic group, pioglitazone group, endothelial progenitor cell transplantation group and combined treatment group. Intravenous injection of endothelial progenitor cell suspension and / or 20 mg/kg pioglitazone was administered intragastrically through tail vein. The levels of blood glucose, serum insulin, serum creatinine, urea nitrogen and 24 h urine protein were measured after 8 weeks of continuous treatment. The survival and distribution of endothelial progenitor cells labeled with CM-Dil were observed by fluorescence microscope and apoptosis of renal cells was detected by Tunel method. Results and conclusion compared with the diabetic group, the levels of blood glucose, creatinine, urea nitrogen and 24 h urine protein in the endothelial progenitor cell group and pioglitazone group were significantly decreased, and the serum insulin level was significantly increased. The levels of blood glucose, serum creatinine, urea nitrogen and 24 h urine protein in the combined treatment group were significantly lower than those in the control group (P 0.01), and the serum insulin level was significantly increased in the endothelial progenitor cells group. The ratio of kidney mass to body mass in pioglitazone group was lower than that in diabetic group (P 0.05), and that in combination group was lower than that in endothelial progenitor cell group. Pioglitazone group (P 0.05) the number of CM-Dil labeled positive cells in the combined treatment group was significantly higher than that in the endothelial progenitor cell transplantation group (n = 4) the number of apoptosis in the normal control group was the least, and that in the diabetic model group was the most, compared with that in the diabetic model group. The number of apoptotic cells in endothelial progenitor cell transplantation group and pioglitazone group was significantly decreased, while that in combination group was further reduced. The results showed that pioglitazone combined with endothelial progenitor cell transplantation could effectively reduce the levels of blood glucose, creatinine, urea nitrogen and 24 h urine protein in rats. Increasing serum insulin level, reducing renal cell apoptosis and improving renal dysfunction in diabetic rats to some extent.
【作者单位】：南阳市中心医院内分泌科;南阳市中心医院重症医学科;南阳市中心医院财务科;南阳市中心医院CT室;
【分类号】：R587.2;R692.9

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