淫羊藿苷抑制Epo启动子高甲基化调控周细胞肌成纤维细胞转化改善5/6肾切除大鼠肾性贫血OA

Objective:To observe the effect of icariin on renal anemia in 5/6 nephrectomized rats and explore its mechanism.Methods:The rats were divided into a sham operation control group,a model control group,a group with 0.6 mg/kg decitabine,and groups with 50 mg/kg and 100 mg/kg icariin.At the end of the 14th week,abdominal aorta blood was taken to detect the blood routine and serum erythropoietin(EPO)levels.Femur and kidney tissue were taken,and the hematopoietic changes of femur bone marrow were observed by hematoxylin-eosin(HE)staining.The co-localized expressions of α-SMA/PDGFRβ in renal tissue were detected by immunofluorescence staining to observe peri-cyte-myofibroblast transition(PMT).Western blot was used to detect the expression of methyltransferase Dnmt 3a,and bisulphite sequencing PCR(BSP)sequencing was employed to detect the methylation level of the Epo promoter.Re-sults:Compared with those of the sham operation control group,the hematological parameters of the model control group were significantly decreased(P<0.01),and the hematopoietic function of bone marrow was decreased.Compared with those of the model control group,the hematological parameters of the groups with 50 mg/kg and 100 mg/kg icariin were significantly elevated(P<0.01),the hematopoietic function of bone marrow was improved,the PMT was increased(P<0.01),the expression of DNA methyltransferase Dnmt 3a and the methylation of Epo promoter were elevated(P<0.01).Compared with that of the model control group,the expression of Dnmt 3a in the groups with 0.6 mg/kg decitabine and 50 mg/kg and 100 mg/kg icariin was significantly decreased(P<0.01),the methylation of Epo promoter and the PMT were decreased,the serum EPO level was significantly increased(P<0.01).Conclusion:Icariin showed an anti-anemic effect in 5/6 nephrectomy-induced rats with chronic kidney disease(CKD),possibly by regulating PMT and restoring EPO production via inhibiting Epo promoter hypermethylation.