XBP1 Inhibitor Can Protect Renal Ischemia-reperfusion Injury

Objective: Endoplasmic reticulum stress response is one of the important mechanisms of renal ischemia-reperfusion injury,IRE1/XBP1 is one of the important pathway.Observing the change of renal function,the expression XBP1?NF-kB in kidney tissues and morphology about the rats through the use of STF083010 of XBP1 inhibitor.To evaluate whether STF083010 has a protective effect for renal ischemia-reperfusion injury and further explore the concrete mechanism.Methods: 30 SD(Sprague Dawley)rats were randomly divided into sham group,I/R group and STF080310 group.After setting up some models of renal-reperfusion injury,we collect the mouse kidney and blood after 24 h reperfusion.Serum urea nitrogen(BUN)and creatinine(Scr)level are assessed by automatic biochemical analyzer test.To assess the extent of damage of renal tissues by PAS.The level of TNF –a and IL–1 in serum are detectable by ELISA.To detect the expression of endoplasmic reticulum stress-related chaperone NF-kB and XBP1 in kidney tissue by the method of immunohistochemical and western blot.The expression of XBP1 ? NF-kB mRNA by using fluorescence Quantitative real-time PCR in three groups.Results: The level of Scr and BUN in I/R group has significant difference compared with sham group(p < 0.05);The level of Scr andBUN in STF083010 group has significant descend compared with I/R group(p < 0.05);The level of TNF-a and IL-1 in I/R group has significant increased compared with sham group(p < 0.05);The level of TNF-a and IL-1 in STF083010 has significant descend compared with I/R group(p < 0.05);PAS straining revealed that STF083010 can significantly attenuated renal dysfunction and histologic damage caused by I/R injury(p<0.05);Immunohistochemical detection showed that STF-083010 group has decreased the level of XBP1 and NF-k B protein compared with I/R group obviously(p<0.05).NF-k B and XBP1 positive cells are mainly distributed in the border area,cortex and medulla,especially the area of proximal renal tubule.QPCR revealed that STF083010 group has decreased the level of XBP1 and NF-kB mRNA compared with I/R group(p<0.05);Western blot detection showed that STF083010 group has decreased the level of XBP1 and NF-k B protein compared with I/R group obviously(p<0.05).Conclusion: Kideny ischemia-reperfusion injury has a close connection with endoplasmic reticulum stress.After ischemia-reperfusion injury,ERS can be initiated and the pathway of IRE1/XBP1 can be started.XBP1,as an important protein,can regulate mechanisms of kidney ischemia-reperfusion injury.STF083010,as an inhibitor of IRE1-XBP1,can reduce renal tubular damage degree through inhibit the levels of XBP1,then the expression of NF-k B,TNF-a and IL-1 will decreased.