The protective effect and mechanism of amitriptyline on sepsis-induced kidney injury / 中国医师杂志

ABSTRACT

Objective To investigate the protective effect and the mechanism of amitriptyline on sepsis-induced kidney injury.Methods 48 male Sprague Dawley (SD) rats were randomly divided into six groupssham group,sham + saline group,sham + amitriptyline group,sepsis group,sepsis + saline group,sepsis + amitriptyline group.Sepsis model was induced by cecal ligation and puncture (CLP).Sham group did not undergo CLP.Amitriptyline were injected subcutaneously to rats with amitriptyline 3 mg/kg before treatment for 10 d,2 times/d,while the control group was injected with the same amount of normal saline.Blood sample was obtained to detect serum level of acid sphingomyelinase (ASMase),ceramide,blood urea nitrogen (BUN),creatinine and interleukin-1β.Malondialdehyde in kidney tissue was determined,and Kidney hematoxylin eosin (HE) staining was performed to observe pathologic change.Another 48 rats were randomly divided into four groupssham group,sepsis group,sepsis + saline group,sepsis + amitriptyline group.The intervention to each group were same as above description.Rats of the four groups were observed for seven days to determine the survival rate.Results The survival rate of rats in sham group were 100％,the survival rate of the sepsis group and the sepsis + physiological saline group was less than 20％,while the survival rate of the sepsis + amitriptyline group was ＞ 50％.The serum concentration of IL-1β,ceramide,BUN,SCr,the activity of ASMase and the level of malondialdehyde (MDA) in kidney tissue were respectively increased in sepsis group,sepsis + saline group and sepsis + amitriptyline group at the 4 time points were significantly higher than the sham groups (P ＜0.01),these indexes in sepsis plus amitriptyline group were significantly decreased compared to sepsis group (P ＜ 0.01).There was no pathologic change in sham group,sham + saline group and sham + amitriptyline group.In sepsis group and sepsis + saline group,general degeneration and necrosis of renal proximal tubular epithelial cells,marked dilatation of renal tubular capsular space,extensive infiltration of inflammatory cells and hemorrhage in renal interstitium were observed.These pathologic changes were obviously reduced in sepsis + amitriptyline group compared with sepsis group.Conclusions Amitriptyline can alleviate sepsis-induced kidney injury,through inhibiting the activity of ASMase and then restraining inflammatory response and oxidative stress in renal tissues.