Protective effect of ulinastatin combined with adipose-derived stem cell transplantation on renal tissues in rats with endotoxic shock / 国际生物医学工程杂志

ABSTRACT

Objective:To investigate the protective effect of ulinastatin combined with adipose-derived stem cells (ADSCs) transplantation on renal tissue in rats with endotoxic shock.Methods:20 Sprague Dawley rats were randomly selected as normal group from 108 Sprague Dawley rats. The remaining 88 rats were treated with 2 ml lipopolysaccharide (10 mg/kg) via tail intravenous injection to establish endotoxic shock model. The established 80 model rats were randomly divided into model group, ADSCs group, ulinastatin group and combination group (ulinastatin combined with ADSCs). All the rats were treated once a day for 3 days. Three days after transplantation, the renal tissues of each group were stained with hematoxylin-eosin staining to observe the pathological changes. The distribution of CM-Dil labeled ADSCs in the kidney of rats was observed by fluorescence microscope. The levels of nitric oxide synthase (NOS), nitric oxide (NO), creatinine and urea nitrogen in rat serum were measured. The reverse transcription PCR and Western Blot were used to detect the level of Bax and Caspase-3 in rat kidney tissue. Three days after transplantation, inflammatory cell infiltration and necrosis were occasionally seen in model group. Compared with the model group, the kidney damage in the ADSCs group and the ulinastatin group was significantly reduced, and kidney damage in the combined group was the least.Results:CM-Dil-labeled positive cells were found by microscope in the ADSCs group and the combined group, while CM-Dil-labeled ADSCs were not found in the kidney tissues of the normal group, model group and ulinastatin group. Compared with the normal group, the levels of NOS, NO, creatinine and urea nitrogen in the model group were significantly increased (all P<0.05). Compared with the model group, the levels of NOS, NO, creatinine and urea nitrogen in the ADSCs group, the ulinastatin group and the combination group were significantly increased (all P<0.05), in which the combined group has a further reduction in these related protein levels than the ADSCs group and the Ulinastatin group (all P<0.05). The mRNA and protein expressions of Bax and Caspase-3 in the kidney tissues of the model group were significantly higher than those in the normal group (all P<0.05). The Bax and Caspase levels in the kidney tissues of the ADSCs group, Ulinastatin group and combination group -3 mRNA and protein expression were significantly lower than those of the model group (all P<0.05), in which the combined group has a further reduction in these related protein levels than the ADSCs group and the Ulinastatin group (all P<0.05). Conclusions:Ulinastatin combined with ADSCs transplantation has a protective effect on kidney damage caused by endotoxin shock, which may be related to alleviating renal cell injury.