摘要
目的:探讨新型大麻素受体1拮抗剂ZH-101-S对糖尿病大鼠肾脏的作用及机制。方法:通过腹腔注射链脲佐菌素建立糖尿病大鼠模型,随机分为糖尿病组和低、中、高剂量组,每组6只,低、中、高剂量组分别于每天腹腔注射0.3,1.0,3.0 mg/kg ZH-101-S,另以健康大鼠作为对照组,对照组和糖尿病组腹腔注射等量生理盐水,8周后检测各组大鼠血尿素氮、血肌酐和尿白蛋白排泄率(urine albumin excretion rate,UAER),测定肾组织丙二醛含量和超氧化物歧化酶(SOD)活力,HE染色观察肾组织病理改变,免疫印迹法检测肾组织细胞电压依赖性离子通道(voltage-dependent anion channel,VDAC)蛋白的表达。结果:与对照组比较,糖尿病组大鼠血肌酐、血尿素氮和UAER明显增高;肾组织SOD活性降低,丙二醛含量升高(P<0.05);肾组织细胞VDAC表达明显降低(P<0.01);肾小球体积增大,肾小管上皮细胞水肿,系膜基质增多。与糖尿病组比较,高剂量组大鼠UAER、血肌酐和血尿素氮明显降低;肾组织SOD活性明显升高,丙二醛含量明显降低;肾脏细胞VDAC表达增加(P<0.05);肾组织病理形态得到一定改善。结论:ZH-101-S对糖尿病肾病大鼠肾脏具有保护作用,可能与抑制氧化应激和改善肾脏线粒体功能有关。
Objective：To investigate the protective effect of novel cannabinoid（CB）1 receptor antago-nist ZH-1 01-S on kidneys in streptozotocin induced diabetic rats.Methods：Diabetic models were estab-lished by intraperitoneal injection of streptozotocin,rats were randomized into diabetes mellitus group（DM group,normal saline,i.p.）,low dose group（0.3 mg/kg ZH-1 01-S,i.p.）,middle dose group（1 .0 mg/kg ZH-1 01-S,i.p.）,and high dose group（3.0 mg/kg ZH-1 01-S,i.p.）;and healthy rats were selected as control group（normal saline,i.p.）.After 8 weeks,the serum urea nitrogen（BUN）,serum creatinine （Scr）,urine albumin excretion rate（UAER）,and the level of malondialdehyde（MDA）and the activity of superoxide dismutase（SOD）in renal tissues were detected;the pathological changes of renal tissues were observed by HE staining;the expression of voltage-dependent anion channel（VDAC）protein in renal tis-sues were examined by Western blotting.Results：Compared with control group,DM group showed higher levels of UAER,Scr and BUN（P〈0.05 ）,decreased SOD activity（P〈0.01 ）,and increased expression of MDA（P〈0.05）;decreased VDAC expression（P〈0.01 ）;glomerular volume increased,renal tubular epithelial cell edema,mesangial matrix increased.Compared with DM group,high dose group had lower levels of UAER,Scr and BUN,increased SOD activity,lower content of malondialdehyde;increased＆nbsp;VDAC expression（P〈0.01 ）,the pathological morphology of the kidney was improved.Conclusion：ZH-1 01-S showed protective effect on the kidney of diabetic rats,which may be related to the inhibition of oxi-dative stress and the improvement of kidney mitochondrial function.
出处
《江苏大学学报（医学版）》
CAS
2016年第5期387-390,共4页
Journal of Jiangsu University：Medicine Edition
基金
镇江市社会发展项目(SH2012038)
关键词
大麻素受体
拮抗剂
糖尿病肾病
氧化应激
电压依赖性离子通道
cannabinoid1receptor
antagonist
diabeticnephropathy
oxidativestress
voltage-de-pendent anion channel
