Effects and mechanisms of Rapamycin on renal interstitial fibrosis in rats

Abstract

Objective To discuss the intervention effects and mechanisms for Rapamycin on renal interstitial fibrosis in rats. Methods A total of 72 Wistar male rats were randomly divided into 3 groups, normal group(n=24), model group(n=24), treatment group(n=24). The model group and treatment group received adenine 200 mg/kg daily, and the treatment group was also given Rapamycin 5 mg/(kg·d) at the 8th day, the normal group was just given the same amount of normal saline for 6 weeks.In the end of the 2nd, 4th and 6th week, 8 rats in each group were sacrificed respectively.The expression of hepatocyte growth factor(HGF), transforming growth factor-β(TGF-β)and neutrophils gelatinases related apolipoprotein(NGAL)in each group were observed.The software of image analysis system was used for semi-quantitative analysis. Results HE and Masson staining results showed that the renal tubular were progressive swelling, and changed with interstitial fibrosis, atrophy and even necrosis in model group from 2 weeks to 6 weeks.The pathological changes of kidney were more ease in the treatment group compared with those in model group.Immunohistochemical staining results showed that HGF expression levels of renal interstitial tissue in model group and treatment group at the 2nd week were significantly higher than those of normal group(P<0.05), and were significantly decreased at the 4th week and 6th week(P<0.05); HGF expression levels of renal interstitial tissue in treatment group were significantly higher than those in model group(P<0.05). NGAL expression levels of renal interstitial tissue in model group and treatment group at the 2nd week were significantly higher than those in normal group(P<0.05), and were significantly decreased at the 4th week and 6th week(P<0.05); NGAL expression levels of renal interstitial tissue in treatment group were significantly higher than those in model group(P<0.05). TGF-β expression levels of renal interstitial tissue in model group and treatment group at the 2nd, 4th, and 6th week were significantly higher than those in normal group(P<0.05), while TGF-β expression levels of renal interstitial tissue in treatment group were significantly lower than those in model group(P<0.05). Conclusion Rapamycin could improve the rat kidney tissue pathology, relieve renal tubular expansion, and slow progression of renal interstitial fibrosis, and has certain protective effect to the kidney. Key words: Rapamycin; Renal interstitial fibrosis; Intervention mechanism