Protective Effect Of Ginsenoside Rbl Against Intestinal Ischemia-Reperfusion Induced Acute Renal Injury In Mice

BackgroundIntestinal ischemia reperfusion (ⅡR) injury is one of the most common pathophysiology mechanisms of trauma and shock. Because of its special environment, structure, metabolic characteristics and important barrier function, intestinal injury induced lung, kidney and liver injury after trauma and shock. Recent studies have shown that Nrf2, as the key transcription factor controls cells against oxidative stress, is an important endogenous protective mechanism. But its role in the intestinal ischemia reperfusion induced renal injury and the mechanism hasn’t been discussed. Ginsenoside Rbl is the main composition of traditional Chinese medicine ginseng. Its "multiple target effect", especially its antioxidant effect is the important mechanism to reduce the multiple organ ischemia-reperfusion injury. However, the pathophysiology and therapeutics of remote organ injury induced by IIR is still a problem. More research about the pathophysiology of Nrf2/ARE pathway in IIR induced remote organ injury and futher understanding of protective mechanisms of ginsenoside Rbl need to be obtained.ObjectiveTo investigate the protective effects and the pathophysiology of Nrf2/ARE pathway of ginsenoside Rbl on IIR induced acute kidney injury (AKI) in mice.Methods1、Male C57BL/6J mice were divided into5groups randomly:①sham group;②Intestinal Ischemia Reperfusion (IIR group);③Normal saline group (NS group);④30mg/kg ginsenoside Rbl (RB1-30group);⑤60mg/kg ginsenoside Rbl (RB1-60group). Intestinal and renal histology was observed and evaluated. Serum DAO, BUN and Scr levels were detected. Renal tissue SOD activity and MDA content were measured.2、Male C57BL/6J mice were divided into6groups randomly:①sham group;②Intestinal Ischemia Reperfusion+NS group (IIR group);③Intestinal Ischemia Reperfusion+RB1(RB1group);④sham+ATRA group;(⑤) Intestinal Ischemia Reperfusion+NS group+ATRA (IIR+ATRA group);⑥Intestinal Ischemia Reperfusion+RB1+ATRA (RB1+ATRA group). Renal histology was observed and evaluated. Serum BUN, Scr and NGAL levels were detected. Renal tissue SOD activity, MDA content, and TUNEL apoptosis, Bcl-2/Bax expression ratio were detected. The expressions of nuclear factor erythroid2-related factor2(Nrf2) and heme oxygenase-1(HO-1) were observed using imunohistochemical and western blot analysis in renal tissue.Results1、Intestinal mucosal injury was evaluated by increased levels of pathological injury score and serum DAO in IIR and NS groups. Renal injury induced by IIR was characterized by increased levels of histological severity score, BUN, Scr and MDA, and decreased level of SOD. All data has no significant difference between IIR group and NS group. Ginsenoside Rbl (30,60mg/kg) lighten renal injury (P<0.01), decrease of DAO, BUN and Scr in serum, MDA levels (P<0.01) in the renal tissues and increase of SOD levels (P<0.01).2、Renal TUNEL-positive cells and the Bcl-2/Bax expression ratio were increased (P<0.01, ⅡR group vs. sham group). The histological injury of kidney was reduced after administration of ginsenoside Rbl. When compared with IIR group, level of SOD was increased, and levels of BUN, Scr, NGAL and MDA were decreased significantly, which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio (P>0.01, RB1group vs. IIR group). Expressions of Nrf2and HO-1in IIR group were increased than those in sham group, and expressions of Nrf2and HO-1in RB1group were much more increaced than those in IIR group (P<0.01). There is no difference when either comparing sham+ATRA with sham group or IIR+ATRA with IIR group. Compared with RBI group, level of SOD was decreased (P<0.01), and BUN, Scr, NGAL and MDA levels were increased (P<0.01) in RBI+ATRA group. What’s more, the nuclear Nrf2expression seemed no significant difference between RBI+ATRA group and in RBI group, but the cytoplasmic HO-1expression was lower between these two groups.ConclusionGinsenoside Rbl attenuates intestinal ischemia reperfusion induced acute renal injury by activating Nrf2/ARE pathway.