去甲斑蝥素对系膜增生性肾炎大鼠干预的研究  

Study of norcantharidin treatment in mesangial proliferative glomerulonephritis rats

作　　者：黄云峰[1] 伍秋霞[1] 韦俏宇[1] 黄亿芸 贺红光[1] 彭小梅[1] 叶琨[1] Huang Yunfeng;Wu Qiuxia;Wei Qiaoyu;Huang Yiyun;He Hongguang;Peng Xiaomei;Ye Kun(Department of Nephrology,The People~ Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021)

机构地区：[1]广西壮族自治区人民医院,南宁530021

出　　处：《中药药理与临床》2018年第4期61-65,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81260121);广西重点研发计划(桂科AB16380229)

摘　　要：目的:观察去甲斑蝥素对系膜增生性肾炎大鼠蛋白尿、肾功能及肾脏病理的影响。方法:SD大鼠BSA隔日灌胃、皮下注射四氯化碳及尾静脉注射脂多糖,建立系膜增生性肾炎模型后分成模型组、去甲斑蝥素0. 15mg/kg、0. 30mg/kg(ip)组;对照组仅腹腔注射等剂量的生理盐水。检测各时间点各组大鼠24小时尿蛋白定量。第8周末处死大鼠,检测血常规及生化指标;肾组织行光镜、电镜和TUNEL染色。结果:与正常对照组比较,模型组各时间点尿蛋白定量、血肌酐(Scr)、血尿素氮(BUN)均显著升高;光镜结果提示肾小球细胞增殖程度积分、系膜基质增生程度、小管间质病理损伤积分亦显著升高;电镜结果显示模型组大鼠肾小球系膜区扩大,系膜区可见基质弥漫增生伴系膜细胞增殖; TUNEL染色提示未见凋亡的系膜细胞。去甲斑蝥素0. 15mg/kg、0. 30mg/kg干预后,肾炎大鼠24小时尿蛋白定量、Scr、BUN均显著降低,且随着干预浓度的增加降低更明显;肾小球细胞增殖程度积分、系膜基质增生程度、小管间质病理损伤积分亦显著降低;系膜区缩小,系膜细胞及基质增殖情况均明显减轻;系膜细胞的凋亡指数AI随着干预浓度的增加而显著升高。各组间丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)及血常规均无差异。结论:去甲斑蝥素能显著降低系膜增生性肾炎大鼠尿蛋白,抑制系膜增生,减轻肾小管间质病理损伤,逆转肾炎大鼠并发的急性肾损伤,且无肝毒性及骨髓抑制等严重不良反应,其作用机制可能与其抑制系膜细胞增殖、促进系膜细胞凋亡有关。Objective： To observe the effects of treatment with norcantharidin（NCTD） on proteinuria,renal function and renal pathology in mesangial proliferative nephritis rats. Methods： SD rats received intragastric administration of bovine serum albumin（BSA） every other day,subcutaneous injection of carbon tetrachloride and tail vein injection of lipopolysaccharide（LPS）,the mesangial proliferative glomerulonephritis rats were randomly divided into model group,low dose of NCTD group（0. 15 mg/kg by intraperitoneally injection） and high dose of NCTD group（0. 30 mg/kg by intraperitoneally injection）; control group was injected with equal dose of saline. Twenty-four-hour urinary protein was measured by 1,4 and 8 weeks. At the end of the eighth week,The rats were sacrificed after anticoagulant blood and serum were collected and remnant kidney of each rat was harvested and weighed for examination of light microscopy、electron microscopy and TUNEL staining. Results：Compared with the control group,urinary protein excretion（24 h）,Serum creatinine（Scr）,Blood urea nitrogen（BUN） increased significantly（P 〈 0. 05 or 0. 01） in model group; Optical microscope showed that proliferation of glomerular cells,hyperplasia of mesangial matrix and tubulointerstitial injury score increased significantly（P 〈 0. 05 or 0. 01） in model group; Electron microscope showed that mesangium region enlarged with mesangial cell proliferation by mesangial matrix hyperplasia in model group; TUNEL staining showed that there wasn’t apoptotic mesangial cells in the mesangial area in model group. After intervention with norcantharidin,urinary protein excretion（24 h）,Serum creatinine（Scr）,Blood urea nitrogen（BUN） decreased obviously（P 〈 0. 05 or 0. 01） in low dose of NCTD group or high dose of NCTD group and with the increase of dose of NCTD intervention to reduce more obvious; Optical microscope indicated that proliferation of glomerular cells 、hyperplasia of mesangial matrix and tubulointersti

关 键 词：去甲斑蝥素 系膜增生性肾炎 急性肾损伤 病理 蛋白尿 

分 类 号：R285.5[医药卫生—中药学]