藏红花红O家兔肾病模型的制备及地塞米松缓释剂的保护作用  

Preparation of saffron red O nephropathy model rabbits and protective effects of dexamethasone sustained-release preparation

作　　者：孙雪梅 吕心蕊 储伟 朱晓筱 周兰兰[1,2] SUN Xue-mei;LYU Xin-rui;CHU Wei;ZHU Xiao-xiao;ZHOU Lan-lan(Dept of Pharmacology, Anhui Medical University, Hefei 230032, China;Dept of Medical College, Shenzhen Polytechnic, Shenzhen 518055, China)

机构地区：[1]安徽医科大学药理学教研室,安徽合肥230022 [2]深圳职业技术学院医护学院,广东深圳518055

出　　处：《中国药理学通报》2021年第10期1409-1415,共7页Chinese Pharmacological Bulletin

基　　金：安徽高校自然科学基金重大项目(No KJ2017ZD18)。

摘　　要：目的研究地塞米松缓释剂(sustained-release of dexamethasone,SR Dex)肾囊内植入给药对藏红花红O家兔肾病模型的保护作用及机制。方法采用耳缘静脉注射臧红花红O的方法建立家兔肾病模型。SR Dex手术肾囊内一次性注射给药(1.48、0.74、0.37 mg·kg^(-1)),阳性对照灌胃给药,连续给药8周。分别于造模前后每周定时检测肾病家兔24 h尿蛋白及血肾功能指标变化;采用PAS染色测肾组织病理损伤;天狼猩红(sirius red,SR)染色测肾组织纤维化程度;免疫组化法测nephrin、TRPC6蛋白表达;Real-time PCR测nephrin、TRPC6蛋白mRNA的变化。结果SR Dex不同剂量组均可降低肾病家兔高尿蛋白、尿素氮和血肌酐的含量;改善肾组织病理学损伤和肾小球内脂类沉积;上调nephrin的表达;下调TRPC6的表达。结论SR Dex对家兔臧红花红O肾病具有良好保护作用,其机制可能与调节肾脏nephrin及TRPC6的表达,增强足细胞滤过屏障功能有关。Aim To study the protective effect and mechanism of SR Dex in safranine O-induced nephritis rabbits.Methods Rabbit nephropathy model was established by injecting safranine O into the ear vein.The disposable administration of SR Dex(1.48,0.74,0.37 mg·kg^(-1))was performed with injection in situ of renal.The positive control treatment group with Dex was given through gastric tube for eight weeks.The changes of urinary protein and blood renal function(serum creatinine and urea nitrogen)in nephrotic rabbits were detected regularly before and after modeling once a week;PAS staining was used to detect the pathological damage of renal tissues;SR staining was used to observe renal tissue collagen fibers,which represented the severity of renal fibrosis;IHC method was carried out to test the protein expression of nephrin and TRPC6.Real-time PCR method was employed to detect mRNA level of nephrin and TRPC6.Results SR Dex treatment groups could reduce 24 h urine protein,serum creatinine,blood urea nitrogen,improve the renal and adrenal histopathological changes,whitch also increased the expression of nephrin protein and decreased the expression of TRPC6 protein in kidney tissues of rabbits with nephropathy.Conclusions SR Dex could improve safranine O-induced nephritis in rabbits.The underlying mechanism might work by inhibiting the down-regulation of nephrin that in turn decreased the expression of TRPC6,improving the integrity of glomerular filtration membrane.

关 键 词：肾病综合征 地塞米松缓释剂 肾囊植入 藏红花红O肾病 NEPHRIN TRPC6 

分 类 号：R-332[医药卫生] R284.1