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目的:观察淫羊藿苷对5/6肾切除大鼠肾性贫血的影响，并探讨其作用机制。方法:将大鼠分为假手术对照组、模型对照组、地西他滨0.6 mg/kg组、淫羊藿苷50、100 mg/kg组。第14周末腹主动脉取血检测血常规及血清促红细胞生成素(EPO)活力；取股骨和肾脏，HE染色观察股骨骨髓造血改变；免疫荧光染色检测肾脏组织α-SMA/PDGFRβ共定位表达，观察周细胞肌成纤维细胞转化(PMT);Western blot法检测肾组织甲基转移酶Dnmt 3a表达；亚硫酸氢测序PCR(BSP)检测Epo启动子甲基化水平。结果:与假手术对照组比较，模型对照组红细胞计数、Hb含量、Hct百分率显著降低(P<0.01),血清EPO活力升高(P<0.05),骨髓造血功能降低，周细胞向肌成纤维细胞转化增多(P<0.01),肾组织DNA甲基转移酶Dnmt 3a表达上调，Epo启动子甲基化表达上调(P<0.01);与模型对照组比较，地西他滨0.6 mg/kg组、淫羊藿苷50、100 mg/kg组血清EPO活力显著升高(P<0.01),红细胞计数、Hb含量、Hct百分率显著升高，肾组织Dnmt3a的表达显著下调(P<0.01),Epo启动子甲基化表达下调，周细胞向肌成纤维细胞转化减少(P<0.01)。结论:淫羊藿苷在5/6肾切除诱导的CKD大鼠中表现出抗贫血作用，其机制可能是通过抑制Epo启动子高甲基化，调控PMT恢复EPO产生，改善肾性贫血。
Abstract：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 pericyte-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. Results: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.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20250408.004
中图分类号:R285.5
引用信息:
[1]袁玲,王蕾,王宏,等.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[J].中药药理与临床,2026,42(02):77-83.DOI:10.13412/j.cnki.zyyl.20250408.004.
基金信息:
天津市卫生健康科技项目(编号：TJWJ2022MS050); 河北省中医药管理局科研计划项目(编号：T2026031)
2025-04-08
2025-04-08
2025-04-08