| Background:Kidney transplantation is the first choice for patients with end-stage renal disease.A high-quality donor kidney is essential for the success of kidney transplantation.Ischemia reperfusion(IR)injury,without a doubt,is inevitable in the process of kidney transplantation.IR injury refers to the situation that the blood perfusion of tissue and organ is restored after ischemia injury,the injury is not reduced but further aggravated.IR injury can not only cause delayed recovery of graft function,but also affect the immune system to promote acute rejection,and directly lead to chronic rejection.Mild hypothermia(MH 30-34℃)can reduce IR injury of tissues and organs.The mechanism of MH alleviating IR injury is various.Objective:Apoptosis and oxidative stress induced by IR injury are important causes of tissue damage.MH can induce organisms to produce cold shock proteins.RNA-binding motif protein 3(RBM3)is one of important cold shock proteins.It can bind to and change the transcription and translation of mRNA.Yes associated protein1(yes-associated protein 1,YAP1)is one of its target proteins,which has anti-apoptosis,anti-hypoxic damage and cell-promoting effects.In this study,rats was used to establish the model of renal IR injury to explore the effect of MH on renal IR injury,as well as the role of MH-induced RBM3 in this process and its mechanism.Methods:Eighteen healthy male SD rats were randomly divided into three groups: Normal control(NC)group,ischemia reperfusion(IR)group,and Mild hypothermia pretreatment with ischemia reperfusion(MHP)group.The rats in the NC group received no special treatment.The rats in the IR group received bilateral renal ischemia for 45 min and reperfusion for 24 h.The rats in the MHP group received the same treatment after 2 hours of MH.Blood and kidney tissue were obtained,renal function was evaluated by detecting serum creatinine value,HE staining was used to detect kidney tissue damage.Western Blot was used to detect the protein levels of RBM3,YAP1,NRF2,Bcl-2,and Bax,and immunohistochemical staining was used to further detect the expression levels and distribution of RBM3 and YAP1.Quantitative Real-time PCR was used to detect the gene expression levels of YAP1 and NRF2.TUNEL method was used to detect kidney cell apoptosis,and tissue MDA content and SOD activity were used to detect tissue oxidative stress.Results:Compared with NC group,serum creatinine value of rats in IR group and MHP group were increased,renal tissue injury,apoptosis degree and oxidative stress injury were significantly increased,protein expression levels of RBM3,YAP1 and Nrf2 were increased,Bcl-2/Bax protein ratio was decreased,and mRNA expression levels of YAP1 and Nrf2 were increased.However,compared with IR group,the serum creatinine value of MHP group was significantly decreased,the renal tissue damage,apoptosis and oxidative stress injury were significantly reduced,and the protein expression levels of RBM3,YAP1,Nrf2 and Bcl-2/Bax were increased,and the gene expression levels of YAP1 and Nrf2 were increased.Conclusion:In this study,MH has a protective effect on renal IR injury in rats,and can reduce the cell apoptosis and oxidative stress injury caused by IR injury.The mechanism may be related to RBM3 induced by MH and its downstream molecule YAP1,providing a potential target for the treatment of renal ischemia reperfusion injury. |
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