Experimental Study On Renal Senescence And Fibrosis After Acute Kidney Injury Induced By Palbociclib

Objective Acute kidney injury(AKI)is a high risk factor of chronic kidney disease(CKD),but the pathophysiological mechanism of renal fibrosis progression after acute kidney injury is not clear.Cell senescence plays an important role in the development of acute kidney injury and chronic kidney disease.As a cell cycle inhibitor,Palboiclib(Palb)has the effect of inducing cell cycle arrest,inhibiting cell proliferation and inducing cell senescence.However,there is no relative research which was conducted to explore the role of Palb in the transition from AKI to CKD.In this paper,we will apply AKI to CKD mouse model to investigate whether Palb can promote the renal senescence and fibrosis progression after AKI by inducing cell cycle arrest.Method(1)Palb was applied to normal mice to detect the expression of cell proliferation and cell senescence related indicators in mouse kidney tissue,and observe the effect of Palb on cell proliferation and cell senescence.(2)The AKI to CKD mouse model induced by unilateral ischemia and reperfusion(UIRI)was constructed,and Palb was used on the mouse model to detect the indicators related to senescence,fibrosis of mouse kidney tissue after treatment.(3)Previous studies showed that the use of dasatinib combined with quercetin(D+Q)to clear senescence cells in UIRI mouse model can reduce the progression of renal fibrosis.In this study,the changes of renal senescence and fibrosis were observed with Palb after D+Q treatment.Results(1)After application of Palb in normal mice,it was found that P16 and P21 were up-regulated in kidney tissue,and the senescence marker SA-β-Gal expression increased,Ki-67 and Lamin B1 expression decreased.(2)After applying Palb in the UIRI mouse model,it was found that the expression of P16 and P21 mRNA,the expression of Collagen I and FN mRNA were up-regulated in kidney tissue.Immunohistochemical staining of renal tissue showed that the expression of Collagen I and FN protein increased.(3)Applying D+Q to clear senescence cells in UIRI mouse model can reduce the expression of renal senescence and renal fibrosis markers.On this basis,applying Palb,compared with using D+Q alone,it was found that the expression of p16 and p21 mRNA in renal tissue is increased,and the expression of fibrosis markers α-SMA,Collagen I and FN mRNA was up-regulated,and the expression level of fibrosis marker protein in renal tissue was increased.Conclusion Palb promotes renal senescence and fibrosis progression by inducing renal cell cycle arrest and inhibiting cell proliferation after AKI,and accelerates the transformation from AKI to CKD.