Metformin attenuates acute liver injury and inflammatory response induced by D-galactosamine in combination with Pam3CSK4 in SD rats / 西安交通大学学报(医学版)

ABSTRACT

Objective To investigate the anti-injury and anti-inflammation protective effects of metformin in acute-liver-injury SD rat model induced by D-galactosamine and Pam3CSK4 .Methods Eighteen male Sprague-Dawley rats were treated with the mixture of D-galactosamine (350 mg/kg ) and Pam3CSK4 (50 μg/kg ) by intraperitoneal injection (i .p .) to construct acute liver injury model .The rats in intervention group were given PBS and metformin ,respectively .The liver and body weight were measured and the ratio of liver weight to body weight was calculated .HE staining was used to observe the pathological changes of the liver .Fasting serum was collected for detection of serological parameters .ELISA and RT-qPCR were used to determine the expression levels of IL-6 and TNF-α.Finally , activation of MAPK signal pathway in rat liver was detected by Western blot .Results Compared with those in control group , the ratio of body weight to liver weight , serum transaminase and proinflammatory cytokines IL-6 and TNF-a were all significantly increased in the two intervention groups .Meanwhile , hepatic degeneration and hepatic interstitial exudation indicated that D -galactosamine combined with Pam3CSK4 successfully constructed acute liver injury model in the SD rats.Compared with PBS group, the ratio of body weight to liver weight , hepatic damage , serum transaminase levels.and the expressions of proinflammatory cytokines IL-6 and TNF-a were significantly decreased in metformin-treated group.Meanwhile,the expressions of p-ERKl/2,p-SAPK/JNK and p-P38 MAPK decreased in liver tissues by metformin pretreatment,suggesting that metformin may play an anti-inflammatory effect by suppressing MAPK signaling pathway.Conclusion Metformin attenuated inflammatory reactions in SD rats with acute liver injury induced by D -galactosamine and Pam3CSK4.