Co-treatment of endothelial progenitor cells and pioglitazone improves kidney function in diabetic rats
10.3969/j.issn.2095-4344.2017.17.013
- VernacularTitle:吡格列酮联合内皮祖细胞移植改善糖尿病肾功能
- Author:
Song WANG
;
Xisheng ZHENG
;
Shan WANG
;
Fang FANG
- From:
Chinese Journal of Tissue Engineering Research
2017;21(17):2702-2707
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Pioglitazone is a common hypoglycemic drug capable of improving proliferation and activation, and inhibiting apoptosis of endothelial progenitor cells (EPCs). We speculated that the combined use of pioglitazone and EPCs transplantation could have significant improving effects on hyperglycemia and kidney function after diabetes mellitus.OBJECTIVE: To investigate the improving effect of EPCs transplantation combined with pioglitazone treatment on the kidney function of diabetic rat models.METHODS: The 15 of 75 Wistar rats were randomly selected and served as normal control group (no treatment). Animal models of type 1 diabetes mellitus were made in the rest 60 rats through the intraperitoneal injection of 40 mg/kg streptozotocin for continuous 5 days. The human EPCs (labeled by CM-Dil) were recovered, cultured and preserved until transplantation. After 4 weeks of modeling, the 60 rat models were randomly divided into model group (PBS injection), pioglitazone group, EPCs transplantation group and combined treatment group, followed by tail vein injection of EPCs suspension and/or intragastric administration of 20 mg/kg pioglitazone for continuous 4 days. After 8 weeks of treatment, the levels of glucose, insulin and creatinine in serum, urea nitrogen and urine protein during 24 hours were determined. The number and distribution of EPCs labeled by CM-Dil were detected by fluorescence microscope, the apoptosis in kidney cells was tested by TUNEL method, and the kidney weight/body weight ratio in rats was calculated.RESULTS AND CONCLUSION: Compared with the model group, the blood glucose and serum creatinine levels and the urea nitrogen and urine protein concentrations during 24 hours were significantly decreased (P < 0.05), and the seruminsulin level was significantly increased (P < 0.05) in the pioglitazone and EPCs transplantation groups. These biochemical indexes in the combined treatment group were more significantly altered compared with the model group (P< 0.01). The kidney weight to the body weight ratio was lowest in the combined treatment group and lower in the pioglitazone and EPCs transplantation groups followed by the model group (P < 0.05). The order of apoptotic kidney cells labeled by TUNEL was as follows: model group > pioglitazone group > EPCs transplantation group > combined treatment group (P < 0.05). To conclude, the EPCs transplantation combined with pioglitazone treatment can decrease the blood glucose and serum creatinine levels and urea nitrogen and urine protein concentrations, improve the serum insulin level, reduce cell apoptosis in the kidney, and remit the kidney dysfunction of diabetic rats to a certain extent.
