Intermedin Inhibits The Transition Of Acute Kidney Injury To Chronic Kidney Disease By Protecting Peritubular Capillaries

Objective:In this study,we aim to see how intermedin(IMD)affects peritubular capillaries(PTC)and whether it can slow down the progression of acute kidney injury(AKI)to chronic kidney disease(CKD).We also want to find out if IMD can slow down AKI’s progression to CKD by stabilizing the number of PTC and reducing renal interstitial fibrosis.Methods:Male IMD gene knockout(IMD-KO)mice with a C57BL/6J background and male same-nest wild-type(IMD-WT)mice were randomly divided into control group and model group,respectively.In the control group,the left renal pedicle was separated,the abdomen was closed,and the right kidney was removed 14 days later.In the model group,the left renal pedicle was separated and clamped for 21 minutes to create an ischemia-reperfusion injury(IRI)model,and the right kidney was removed 14 days later.On the 14 th day after the right nephrectomy,the left kidney was resected and collected.Masson staining was used to observe renal fibrosis.Immunohistochemical staining was used to detect the expression level of CD31 in renal tissues to evaluate the number of PTC vessels.Western blot was used to detect the expression of vascular endothelial growth factor A(VEGFA)protein in kidney tissue.RT-PCR was used to detect the expression of VEGFA m RNA and HIF-1α m RNA in renal tissue.Results:Masson staining showed that kidney fibrosis was mild in the IMD-KO control group compared with the IMD-WT control group(P>0.05).Compared with the corresponding control group,the degree of fibrosis in IMD-WT mice and the IMD-KO model group was heavier(P<0.05),and the degree of renal fibrosis in the IMD-KO model group was more obvious than that in the IMD-WT model group(P<0.05).Immunohistochemical staining revealed that,as compared to the IMD-WT control group,CD31 protein expression was lower in the IMD-KO control group(P<0.05).Compared with the corresponding control group,the expression of CD31 protein in IMD-WT model group and the IMD-KO model group was significantly decreased(P<0.05).Compared with the IMD-WT model group,the expression of CD31 protein in the IMD-KO model group was significantly decreased(P<0.05).RT-PCR and western blot showed that the expression of VEGFA in the IMD-KO control group was decreased compared with that in the IMD-WT control group(P<0.05).The expressions of VEGFA in IMD-WT model group and the IMD-KO model group were significantly decreased(P<0.05),while the expressions of VEGFA in the IMD-KO model group were significantly decreased compared with that in the IMD-WT model group(P<0.05).RT-PCR also showed that the expression of HIF-1α in the IMD-KO control group was decreased compared with that in the IMD-WT control group(P<0.05).Compared with the corresponding control group,the expression of HIF-1α in the IMD-WT model group and the IMD-KO model group was significantly increased(P<0.05).Compared with IMD-WT in model group,the expression of HIF-1α in the IMD-KO model group was lower(P<0.05).Conclusion:(1)IMD can prevent the decrease of PTC density in the transition of AKI to CKD and inhibit AKI’s transition to CKD;(2)IMD can up-regulate the expression of HIF-1α and VEGFA,which may be an important mechanism to protect PTC and prevent AKI’s transition to CKD.