地塞米松缓释剂肾囊植入对阿霉素肾病大鼠的保护作用  

Protective effects of dexamethasone controlled release agent through renal capsule injection in adriamycin-induced nephritic rats

作　　者：秦志强 范慢利 王坤[1] 章成 周兰兰[1,3] Qin Zhiqiang;Fan Manli;Wang Kun(Dept of Pharmacology,Anhui Medical University,Hefei 230032;Fuyang Hospital of Anhui Medical University,Fuyang 236000)

机构地区：[1]安徽医科大学药理学教研室,合肥230032 [2]安徽医科大学附属阜阳医院,阜阳236000 [3]深圳职业技术学院医护学院,深圳518055

出　　处：《安徽医科大学学报》2021年第6期932-937,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金面上项目(编号:81870957)。

摘　　要：目的研究了一种新的糖皮质激素缓释植入剂(DexI)对阿霉素肾病大鼠的治疗作用。方法大鼠尾静脉注射阿霉素,总剂量7.5 mg/kg,隔周注射,连续2周,制备肾病模型。模型组采用地塞米松一次性肾囊植入剂给药(2.8、1.4、0.7 mg/kg),阳性对照组采用地塞米松(0.1 mg/kg,qd)灌胃给药,连续给药8周。造模前后定期收集血清、尿液检测肾功能和24 h尿蛋白。实验结束后取肾脏标本,进行病理组织学检查、免疫组织化学分析,并检测肾脏足细胞裂孔隔膜Nephrin蛋白的表达。结果DexI可不同程度改善阿霉素肾病大鼠的一般状况,防止体质量下降,表现出较好的精神状态;DexI还可显著降低肾病大鼠24 h尿蛋白,改善肾功能(降低血肌酐及尿素氮水平),对抗阿霉素引起的肾脏病理损害。结论地塞米松缓释植入剂可显著改善阿霉素诱导的大鼠肾脏损伤,可能与其增强足细胞的滤过屏障功能有关。Objective To investigate the curative effects of a new sustained release agent of glucocorticoid on doxorubicin-induced nephropathy rats.Methods The nephrotic model was prepared by injecting doxorubicin into caudal vein in rats with a total dose of 7.5 mg/kg for two consecutive weeks.The test group was given dexamethasone implant(DexI,2.8,1.4,0.7 mg/kg)one time through renal capsule injection,while the intragastric administration of dexamethasone(Dex,0.1 mg/kg,qd)for 8 weeks was used as a positive control.Serum and urine were collected regularly before and after modeling to detect renal function and 24 h urine protein.After the experiment,kidney specimens were taken for histopathological examination,immunohistochemical analysis and the expression of nephrin protein in the ruptured septum of renal podocytes.Results DexI could improve the general condition of rats with adriamycin nephropathy to different degrees,prevent weight loss and show a better mental state;DexI could also significantly reduce the 24 h urine protein in kidney rats and improve kidney function(reduce blood creatinine and urea nitrogen levels);DexI could fight kidney pathological damage caused by doxorubicin.Conclusion Sustained-release dexamethasone implants can significantly improve doxorubicin-induced kidney injury in rats,which may be related to its enhancement of the podocyte filtration barrier barrier function.

关 键 词：阿霉素肾病 地塞米松缓释剂 肾囊植入 足细胞 滤过屏障 

分 类 号：R961[医药卫生—药理学]