银杏叶提取物、α-硫辛酸对糖尿病大鼠肾组织中糖基化终产物及其受体RAGE表达的影响

Extract of Ginkgo biloba and α-lipoic Acid Attenuate Advanced Glycation End Products Accumulation and RAGE Expression in Diabetic Nephropathy Rats

免费下载全文查看/发表评论下载PDF阅读器

DOI：

中文关键词: 糖尿病肾病糖基化终产物糖基化终产物受体银杏叶提取物 α-硫辛酸

英文关键词:diabetic nephropathy advanced glycation end products receptor for advanced glycation end products extract of Ginkgo biloba,α-lipoic acid

基金项目:上海市卫生局青年科研基金项目(No.2009Y081)

作者	单位
严海东	同济大学附属东方医院肾内科
王俊	同济大学附属东方医院肾内科
李雪竹	同济大学附属东方医院肾内科
江薇	同济大学附属东方医院肾内科

摘要点击次数: 1952

全文下载次数: 4

中文摘要:

目的探讨糖基化终产物(AGEs)与其受体RAGE在糖尿病肾病(DN)中的表达和作用机制,以及抗氧化剂银杏叶提取物(EGb)、α-硫辛酸(ALA)对其的作用。方法链脲菌素(STZ)60mg/kg一次性腹腔注射建立DN大鼠模型,随机分为DN组(12只,每天腹腔注射生理盐水),EGb组[14只,给予EGb(300mg/kg)隔天口服治疗]和ALA组[12只,给予ALA(35mg/kg)隔日腹腔注射],另外10只大鼠以腹腔注射柠檬酸(60mg/kg)作为正常对照组。分别于第12周和第20周处死动物。检测体重、血糖、肾功能、24h尿蛋白定量,PAS染色观察肾组织结构改变,分光光度仪检测氧化应激指标,荧光分光光度法检测AGEs含量,RT-PCR、Western blot检测RAGE表达水平。结果与正常对照组比较,第12周和20周DN大鼠24h尿蛋白定量增高,肾小球滤过率增加。病理组织染色示肾小球系膜扩张、基质增生、肾小管上皮空泡变性等改变。肾组织匀浆脂质过氧化产物丙二醛(MDA)水平、尿中DNA氧化损伤标志物8-羟基脱氧鸟苷(8-OHdG)水平增加,过氧化物酶(CAT)、还原型谷胱甘肽(GSH)水平下降。血清及肾组织匀浆AGEs含量增加,RAGE mRNA和蛋白表达水平增加。EGb组和ALA组24h尿蛋白定量减少,病理病变减轻,MDA和8-OHdG水平下降,CAT和GSH增加,AGEs含量减少,RAGE表达下调。结论 DN时循环和肾组织局部AGEs含量增高,RAGE表达上调。EGb和ALA可通过减少氧化应激而抑制AGEs生成及下调RAGE表达,进而改善DN大鼠肾组织结构和肾功能,在防治DN方面有良好的应用前景。

英文摘要:

Objective To investigate the accumulation of advanced glycation end products(AGEs) and expression of receptor for AGEs(RAGE) in streptozocin(STZ)-induced diabetic nephropathy in rats,and the role of antioxidants on the AGEs-RAGE signaling.Methods Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg,and randomly divided into the DN group(n=12,treated with normal saline by intraperitoneal injection,once daily),the extract of Ginkgo biloba(EGb) group(n=14,treated with EGb 300 mg/kg by oral administration,once every other day),and the α-lipoic acid(ALA) group(n=12,treated with ALA at the dose of 35 mg/kg by intraperitoneal injection,once every other day).Rats of the normal control group(n=10) were given vehicle citrate buffer at the dose of 60 mg/kg.Rats were sacrificed at the 12th week and the 20th week of this study.The four groups were compared in terms of body weight,blood glucose,renal function,24-h urine protein.Renal pathological changes were observed by PAS staining.Oxidative stress indices were detected using spectrophotometry.The concentrations of AGEs were measured using fluorospectrophotometry,and the expressions of RAGE were detected by Real-time PCR and Western blot.Results Compared with the normal control group,the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week.The pathological tissue staining showed dilated glomerular mesangium,proliferated glomerular matrix,vacuolar degeneration of the renal tubular epithelium.Malonaldehyde(MDA) levels and 8-hydroxide radical guanine deoxyriboside(8-OHdG) levels increased,and catalase(CAT) and reduced glutathione hormone(GSH) levels decreased.The AGEs contents in serum and renal tissue homogenate increased.The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week.The 24-h urine protein quantitation was reduced in the EGb group and the ALA group,with alleviated pathological changes,lowered MDA and 8-OHdG levels,increased CAT and GSH levels,decreased AGEs contents,and down-regulated RAGE expressions.Conclusions AGEs contents increased and RAGE expression up-regulated in the circulation and local renal tissues in DN rats.EGb and ALA could inhibit AGEs production and down-regulate RAGE expressions by reducing oxidative stress,thus further improving the renal tissue structure and renal functions of DN rats.It had better application prospect in treatment and prevention of DN.

关闭