1.Protective effect of dulaglutide against sepsis⁃induced acute kidney inj ury in mice
Fengyi Deng ; Yue Wang ; Xingyu Fan ; Hujing Deng ; Xing Zhong ; Yijun Du ; Hong Su ; Tianrong Pan
Acta Universitatis Medicinalis Anhui 2023;58(8):1329-1334
Objective :
To investigate the protective effect of dulaglutide on acute kidney injury (AKI) induced by
lipopolysaccharide (LPS) .
Methods :
Twenty⁃four male C57BL/6 mice were randomly divided into Control group (normal saline) , LPS group (LPS 15 mg/kg) , LPS + Dul group (LPS 15 mg/kg + Dulaglutide 0. 6 mg/kg) and Dul group (Dulaglutide 0. 6 mg/kg) with 6 mice in each group. The drug was administered by intraperitoneal injection. After drug intervention for 24 h , the body weight and kidney weight of mice were recorded , and kidney tissue and serum samples were collected. The pathological changes in kidney tissue were observed by HE staining.
The serum urea nitrogen (BUN) and creatinine (CRE) levels were detected by the kit. The levels of cytokines interleukin (IL⁃6) , tumor necrosis factor (TNF⁃α ) and IL⁃1β in the kidney were detected by qRT⁃PCR. The contents of macrophage marker F4/80 and myeloperoxidase (MPO) in kidney were determined by immunohistochemistry.
Results :
Compared with Control group , mice in LPS group lost weight and increased kidney weight ( P <
0. 001) . Moreover, the levels of BUN and CRE increased (P < 0. 001 , P < 0. 01) . Meanwhile , the mRNA levels of IL⁃6 , IL⁃1β and TNF⁃α increased (P < 0. 05) . There was obvious pathological damage in kidney tissue. In addition , macrophage and neutrophil infiltration increased in LPS group ( P < 0. 001) . Compared with LPS group , mice in LPS + Dul group gained weight and lost kidney weight (P < 0. 05 , P < 0. 001) . Moreover, the levels of BUN and CRE in LPS + Dul group decreased (P < 0. 01) . The renal histological scores were reduced (P < 0. 05) . In addition , the levels of IL⁃6 , IL⁃1β and TNF⁃α in kidney tissue decreased (P < 0. 05 or P < 0. 01) . Moreover, the infiltration of macrophages and neutrophils in kidney was reduced (P < 0. 01) .
Conclusion
Dulaglutide has a protective effect on LPS⁃induced sepsis AKI , which may be related to reduce the expression of inflammatory media⁃ tors and decrease the infiltration of inflammatory cell.