Sleeve gastrectomy attenuates diabetic nephropathy by upregulating nephrin expressions in diabetic fatty rats

Abstract BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and sleeve gastrectomy (SG) is considered to be an effective strategy to improve pre-existing DN. However, the mechanism remains unknown. METHODS: Animal model of DN was induced by high fat diet (HFD) and streptozotocin (STZ). SG or sham surgery was performed and rats were sacrificed at 4, 8 and 12 weeks after surgery. The basic parameters(blood glucose, body weight, kidney weight), indicators of renal function including serum creatinine(Scr), blood urea nitrogen(BUN), urine microalbumin, urine creatinine(Ucr), microalbumin creatinine ratio(UACR), ultrastructural changes of glomerulus and the expression of nephrin gene and protein in glomerular podocytes were compared among groups. RESULTS: Blood glucose and body weight of SG rats were significantly lower than those of the sham-operated rats, and renal function of SG group were also significantly improved within the postoperative period of 12 weeks. The results of Periodic acid-Schiff staining(PAS) and transmission electron microscopy(TEM) showed that glomerular hypertrophy and accumulation of extracellular matrix proteins were significantly alleviated after SG, and the thickness of basement membrane and the fusion or effacement of foot processes were also significantly improved. The mRNA and protein expression of nephrin in SG group was significantly higher than that in the Sham group. CONCLUSIONS: These results suggest that SG attenuates DN by upregulating the expression of nephrin and improving the ultrastructure of glomerular filtration membrane