Autophagy Is Involved In The Protective Effect Of Rapamycin On Renal Allograft Injury In Rats

Aims: Rapamycin has potential beneficial effects on interstitial fibrosis and inflammatory cell infiltration in various models of kidney injure. However, its role in renal allograft injury has not been well-defined. This study aimed to investigate whether rapamycin exerts protective effect on tubular atrophy and interstitial fibrosis in a rat model of kidney transplantation. Methods: Recipients were divided into three groups after kidney transplantation: isograft, allograft, and allograft treated with 0.8 mg/kg/d rapamycin. Grafts were harvested at 4 and 8 weeks post-transplantation, and renal function and histopathology were examined. Grafts were also evaluated by electron microscopy. The autophagy-associated molecules LC3-II, Beclin-1, and p62 were measured using western blot analyses, immunohistochemistry, and immunofluorescence staining. Results: Serum creatinine levels were increased significantly at 8 weeks after kidney transplantation. This increase was diminished in the rapamycin group compared with the allograft group (P < 0.05). Histopathology revealed less kidney damage and interstitial collagen deposition at 4 and 8 weeks after transplantation in the rapamycin group compared to the allograft group (P < 0.05). Expression levels of the autophagy markers LC3-II and Beclin-1 were higher, and p62 levels were lower, around tubules in the rapamycin group at 4 and 8 weeks compared to the allograft group (P < 0.05). Furthermore, immunofluorescence staining and electron microscopic analysis showed that rapamycin increased the LC3-II level and autophagic vacuoles, at 8 weeks compared to the allograft group (P < 0.05). Conclusions: Rapamycin may effectively reduce the progression of renal interstitial fibrosis and tubular atrophy in rats following kidney transplantation. These effects occur, at least in part, by increasing autophagy around the renal tubules.