| Objective: Renal ischemia-reperfusion injury refers to the phenomenon that renal blood supply is restored after various injuries,while renal function cannot be restored,and tissue damage is further deteriorated.Renal ischemia-reperfusion injury is often caused by shock,acute renal artery obstruction,and kidney transplantation caused by various reasons.It is one of the main causes of acute kidney injury and acute renal failure.The role of autophagy in acute kidney injury has received considerable attention.Numerous studies have proved that autophagy has the effect of reducing kidney damage,and some studies have shown that in acute kidney injury,autophagy will instead increase tissue damage.In this study,we used SD(Sprague Dawley)rat to evaluate a renal ischemia-reperfusion injury model.The changes of renal function,the expression of Beclin-1 and LC3 in renal tissue and the changes of histomorphology of renal tissue in rats with renal ischemia-reperfusion injury by using STF083010 to evaluate whether STF083010 has protective impact of renal ischemia-reperfusion injury,and to preliminarily explore the protective mechanism of autophagy on renal ischemia-reperfusion injury.Methods: Firstly,the model of renal ischemia/reperfusion injury of rat was formed.Thirty healthy male SD rats were selected and randomly broke down into sham-operated(sham)group,I/R group and STF080310 group.The rats were killed 24 hours after reperfusion,and the blood and renal tissues were retained.The levels of serum creatinine(Scr)and urea nitrogen(BUN)of the three groups of rats were monitored by an automatic biochemical instrument.The pathological changes of renal tissues in the three groups were subjected to hematoxylin and eosin(HE)staining,and the expression of Beclin-1 and LC3 protein in renal tissue was detected by immunohistochemical method.Results: Renal function tests showed that the levels of serum creatinine and urea nitrogen in I/R group were strikingly higher than those in the sham group(98.07±17.80 vs 28.89±4.83μmol/l,P<0.05;27.73±3.89 vs 6.44±1.11 mmol/l,P<0.05).And the levels of serum creatinine and urea nitrogen in STF083010 group were remarkably lower than those in I/R group(40.36±9.23 vs 98.07±17.80μmol/l,P<0.05;18.45±3.78 vs 27.73±3.89 mmol/l,P<0.05).HE staining showed that the renal tissue samples of I/R group showed edema of renal tubules,hyperemia in lumen and even exfoliation of renal tubular epithelial cells could be seen under the light microscope.The injury of renal tissue in STF083010 group was noticeably less than that in I/R group,and the score of renal injury necrosis was also shown(3.25±0.31 vs 1.83±0.48,P<0.05).Under the light microscope,the edema of renal tubules and the exfoliated number of renal tubular epithelial cells were markedly reduced in STF083010 group.Immunohistochemical results showed that in parallel with the sham group,the rates of Beclin-1 and LC3 positive cells increased considerably after 24 hours of reperfusion in I/R group(0.18±0.01 vs 0.45±0.17,P<0.05;0.21±0.18 vs 0.53±0.11,P<0.05).By contrast,the rate of Beclin-1 and LC3 positive cells was obviously lower in STF083010 group than in I/R group,and the difference was statistically significant(0.45±0.17 vs 0.29±0.12,P﹤0.05;0.53±0.11 vs 0.36±0.06,P<0.05).Conclusions: As an inhibitor of XBP1,STF083010 can narrow the degree of renal tubular injury and mediate the decrease of the expression of Beclin-1 and LC3 by inhibiting autophagy. |
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