Abstract
To evaluate the effects of sirolimus (SRL) on renal injury in rats with bile duct ligation. A total of 21 male Sprague-Dawley rats weighing 220-260 g were used. Group 1 (Sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n=7) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/SRL, n =7) received a daily dose of sirolimus (0.5 mg·day(-1) x kg(-1) dissolved 1 ml in saline) by orogastric tube for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation were processed. AST, ALT, AP and TB levels values were decreased in group 3 when compared to group 2. There was no significant difference in serum levels of BUN and creatinine among all the experimental groups. Histological evaluation of the liver of BDL/Untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. In BDL/SRL group, moderate damage was seen. Tubular injury scores were higher in the BDL subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. In group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. Sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. The improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney.
Highlights
Patients with obstructive jaundice may have a higher incidence of renal dysfunction and approximately 6%-8% of patients suffer from acute renal injury, with a mortality of over 68%1,2
The purpose of the present study is to investigate the effects of sirolimus on renal injury in bile duct-ligated (BDL) rats
The bile duct ligation resulted in jaundice in rats
Summary
Patients with obstructive jaundice may have a higher incidence of renal dysfunction and approximately 6%-8% of patients suffer from acute renal injury, with a mortality of over 68%1,2. Causes underlying of the renal morphological and functional changes in obstructive jaundice still not been understood. Renal excretory function diminishes, with decreases in glomerular filtration rate and renal sodium excretion[6]. The action of SRL is due to blockade of mammalian target of rapamycin (mTOR)[9]. It has a critical role in promoting cellular growth and differentiation, cell cycle progression, apoptosis and organ size[10,11]
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