苯磺酸左旋氨氯地平对慢性肾脏病合并原发性高血压大鼠的肾脏保护研究  

Renal protection of L-amlodipine besylate spontaneously hypertensive rats with chronic kidney disease

作　　者：侯静 蔺艳 刘勇 王玉洁 HOU Jing;LIN Yan;LIU Yong;WANG Yujie(Department of Geriatrics,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Institute of Oncology,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Pathology,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Nephrology,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学附属医院老年科,四川泸州646000 [2]西南医科大学肿瘤研究所,四川泸州646000 [3]西南医科大学附属医院病理科,四川泸州646000 [4]西南医科大学附属医院肾病内科,四川泸州646000

出　　处：《世界临床药物》2022年第5期542-548,共7页World Clinical Drug

基　　金：四川省医学会科研课题(2016SHD005)。

摘　　要：目的探究苯磺酸左旋氨氯地平对慢性肾脏病(chronic kidney disease,CKD)合并原发性高血压大鼠(spontaneously hypertensive rats,SHRs)肾脏保护作用及其机制。方法选取40只雄性SHRs,随机抽样分为假手术组、模型对照组、苯磺酸左旋氨氯地平常规剂量组(A组,一日2.5 mg/kg)和高剂量组(B组,一日5 mg/kg),每组10只,除假手术组外,在SHRs上建立CKD模型。给予各组大鼠标准喂养及相应灌胃处理,每2周行尾动脉测压;检测各组24 h尿蛋白定量,肾功能指标[血清肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)],血清炎症指标[超敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]及氧化应激指标[丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)]水平。行肾脏病理苏木精-伊红染色、Masson染色及过碘酸希夫染色,观察各组大鼠肾脏组织病理改变。结果给药6周后,A、B组收缩压及舒张压较模型对照组明显降低,且B组优于A组(P<0.05)。模型对照组24 h尿蛋白定量、Scr及BUN高于假手术组(P<0.05),A、B组低于模型对照组,且B组低于A组(P<0.05)。模型对照组较假手术组血清hs-CRP、IL-6、TNF-α及MDA水平升高,SOD水平降低(P<0.05);A、B组较模型对照组改善,且B组优于A组(P<0.05)。假手术组肾脏病理结构未见明显异常,B组肾脏病理结构变化及损伤轻于A组,A组轻于模型对照组。结论苯磺酸左旋氨氯地平可降低CKD的SHRs血压,减轻肾脏病理变化,延缓肾功能恶化速度,机制可能为通过改善机体微炎症及氧化应激状态保护肾脏,延缓CKD进展。Objective To investigate the renal protective effects of L-amlodipine besylate on chronic kidney disease(CKD) spontaneously hypertensive rats(SHRs) and its mechanism.Methods A total of 40 male SHRs were randomly divided into sham operation group,model control group,routine dose group of L-amlodipine besylate(group A,2.5 mg/kg one day) and high dose group(group B,5 mg/kg one day),with 10 SHRs in each group.Except for sham operation group,CKD model was established on SHRs.SHRs in each group were given standard feeding and corresponding gavage treatment,and tail artery manometry was performed every 2 weeks.The 24-hour urinary protein,renal function indexes[serum creatinine(SCR),blood urea nitrogen(BUN)],serum inflammatory indexes[high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)]and oxidative stress indexes[malonaldehyde(MDA),superoxide dismutase(SOD)]were measured.The renal pathological changes of rats in each group were observed by hematoxylin eosin staining,Masson staining and periodic acid Schiff stain.Results After 6 weeks of administration,the systolic and diastolic blood pressure in groups A and B were lower than those in the model control group,and group B was better than group A(P<0.05).The 24-hour urinary protein,Scr and BUN in the model control group were higher than those in the sham operation group(P<0.05),those in groups A and B were lower than those in the model control group,and those in group B were lower than those in group A(P<0.05).Compared with the sham operation group,the serum hs-CRP,IL-6,TNF-α and the level of MDA in the model control group increased significantly,and the level of SOD decreased (P<0.05),group A and group B were both better than the model control group,and group B was better than group A(P<0.05).No obvious abnormality was found in the renal pathological structure of the sham operation group.The renal pathological structure changes and damage in group B were lighter than those in group A,and those in group A were lighter than

关 键 词：苯磺酸左旋氨氯地平 慢性肾脏疾病 高血压 炎症反应 氧化应激 

分 类 号：R9724[医药卫生—药品] R544.1[医药卫生—药学] R692.3