| ObjectiveTo evaluate the relationship between lipoxin A4 and the endogenous protection mechanism of acute kidney injury induced by renal ischemia reperfusion(I/R)injury in rats.MethodsTwenty-four pathogen-free male SD rats were randomly divided into 4 group(n=6): sham group(group sham),renal ischemia reperfusion(I/R)injury group(group I/R),lipoxin A4 group(group LXA4)and lipoxin A4 receptor inhibitor Boc-2 group(group Boc-2).Renal ischemia-reperfusion injury model was established by excising the right renal and transiently clamping the left renal artery.In group sham,only right kidney was removed.In group I/R,excising the right renal and transiently clamping the left renal arteryin group I/R.In group LXA4,LXA4(200 μg/kg)was injected via tail vein respectively at 36 h,24 h and 12 h before renal I/R.In group Boc-2,Boc-2(100 mg/kg)was injected via tail vein respectively at 36 h,24 h and 12 h before renal I/R,and thanLXA4(200 μg/kg)was injected 6 hours after each Boc-2 administration.24 h after reperfusion,the serum creatinine(Scr)and blood urea nitrogen(BUN),superoxide dismutase(SOD)and malondialdehyde(MDA)from renal cortex was measured,expression of cleaved caspase-3,Bcl-2,Mfn2,VDAC1 and cytochrome C was detected by western blot.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were measured by enzyme linked immunosorbent assay(ELISA).Results1.Compared with group sham,Scr was increased in group I/R(P<0.001),group LXA4(P=0.035)and group Boc-2(P<0.001);BUNwas increased in group I/R(P<0.001),group LXA4(P=0.019)and group Boc-2(P < 0.001);Compared with groupI/R,Scr(P<0.001)and BUN(P<0.001)was decreased in group LXA4;Compared with groupLXA4,Scr(P=0.004)and BUN(P=0.003)was increased in group Boc-2.2.Compared with group sham,SOD was increased in group I/R(P<0.001),group LXA4(P=0.044)and group Boc-2(P<0.001);while MDA was decreased in group I/R(P<0.001),group LXA4(P=0.033)and group Boc-2(P=0.001);Compared with groupI/R,SOD(P=0.003)was decreased and MDA(P=0.001)was increased in group LXA4;Compared with group LXA4,SOD(P=0.04)was increased and MDA(P=0.004)was decreased in group Boc-2.3.Compared with group sham,the expression of cleaved caspase-3 was increased in group I/R(P<0.001),group LXA4(P<0.001)and group Boc-2(P<0.001);while Bcl-2 was decreased in group I/R(P<0.001),group LXA4(P<0.001)and group Boc-2(P < 0.001);Compared with groupI/R,cleaved caspase-3(P < 0.001)was decreased and Bcl-2(P<0.001)was increased in group LXA4;Compared with groupLXA4,cleaved caspase-3(P<0.001)was increased and Bcl-2(P<0.001)was decreased in group Boc-2.4.Compared with group sham,the expression of Mfn2 was decreased in group I/R(P<0.001),group LXA4(P=0.047)and group Boc-2(P<0.001);VDAC1 was decreased in group I/R(P<0.001),group LXA4(P=0.003)and group Boc-2(P<0.001);while cytochrome C was increased in group I/R(P<0.001),group LXA4(P=0.003)and group Boc-2(P<0.001);Compared with groupI/R,Mfn2(P=0.020)and VDAC1(P=0.001)was increased,and cytochrome C(P=0.002)was decreased in group LXA4;Compared with groupLXA4,Mfn2(P=0.003)and VDAC1(P<0.001)was decreased,and cytochrome C(P=0.014)was increased in group Boc-2.5.Compared with group sham,TNF-α(P<0.001),IL-6(P=0.001)and IL-1β(P=0.001)was increased in group I/R;Compared with group I/R,TNF-α(P=0.004),IL-6(P=0.031)and IL-1β(P=0.032)was decreased in group LXA4;Compared with group LXA4,TNF-α(P=0.014),IL-6(P=0.023)and IL-1β(P=0.025)was increased in group Boc-2.Conclusion1.Scr and BUN levelswas increased after renal I/R in rat;Scr and BUN levels was decreased by pretreatment with lipoxin A4;Boc-2 can reversed the role of lipoxin A4.2.SOD levels was increased and MDA levels was decreased after renal I/R in rat;SOD levels was decreased and MDA levels was increased by pretreatment with lipoxin A4;Boc-2 can reversed the role of lipoxin A4.3.The expression of cleaved caspase-3 was increased and Bcl-2 was decreased after renal I/R in rat;the expression of cleaved caspase-3 was decreased and Bcl-2 was increased by pretreatment with lipoxin A4;Boc-2 can reversed the role of lipoxin A4.4.The expression of cytochrome C was increased,while Mfn2 and VDAC1 was decreased after renal I/R in rat;the expression of cytochrome C was decreased,while Mfn2 and VDAC1 was increased by pretreatment with lipoxin A4;Boc-2 can reversed the role of lipoxin A4.5.TNF-α,IL-6 and IL-1was increased after renal I/R in rat;TNF-α,IL-6 and IL-1β was decreased by pretreatment with lipoxin A4;Boc-2 can reversed the role of lipoxin A4.6.Lipoxin A4 is associated with endogenous protection mechanism induced by renal ischemia-reperfusion in rats and inhibits renal tubular cell apoptosis through thromboxane A4 receptor and alleviates mitochondrial damage and reduces renal ischemia-reperfusion Induced acute renal injury. |
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