OBJECTIVE:To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy,and the potential mechanism underpinned the action.METHODS:F...OBJECTIVE:To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy,and the potential mechanism underpinned the action.METHODS:Forty adriamycin rats were randomly divided into two groups with the ratio of 1︰3;the small-number group served as control group(n=10),and the rats in the large-number group were treated with adriamycin to induce nephropathy;then they were further randomly assigned into 3subgroups:benazepril group(n=10),artemisiningroup(n=10),and adriamycin group(n=10).The benazepril group and artemisinin group were treated with benazepril suspl(5.0 mg/kg daily)and artemisinin suspl(150 mg/kg daily)respectively after being modeled;those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day.The treatment after model establishment lasted for a total of 4 weeks.The 24 h uric protein,blood biochemicals,renal pathological changes,renal ultrastrutural changes,Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay,completely automatic biochemical analyzer,light microscope,electron microscopy,Western blot and reverse transcription polymerase chain reaction,respectively.RESULTS:The rats in adriamycin group showed a significant increase in 24 h uric protein excretion,serum total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),serum creatinine(Scr)and decrease in albumin(Alb)(P<0.05 or P<0.01).Compared with adriamycin group,artemisinin could reduce uric protein excretion,decrease the serum TC,TG elevation,increase the serum Alb level,up-regulate the expressions of Nephrin and Podocin(P<0.05 or P<0.01),but no statistical significance effects on the levels of BUN,Scr in artemisinin group(P>0.05).The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats.CONCLUSION:Artemisinin might have an effe展开更多
文摘目的探讨厄贝沙坦对糖尿病大鼠尿蛋白以及足细胞、足突顶膜区主要的带负电荷跨膜蛋白Podocalyxin的影响。方法采用链脲佐菌素(streptozotocin STZ,65mg/kg)腹腔注射建立糖尿病大鼠模型。将30只雄性SD大鼠随机分为3组:正常组、糖尿病模型组和厄贝沙坦(ARB)治疗组。连续监测血糖8周,8周后处死各组大鼠的前一天行24小时尿蛋白定量和肾功检查了肾组织;处死大鼠后取行苏木素伊红染色(hematoxylin and eosin stain,HE)观察其病理变化;透射电镜观察足细胞、裂孔隔膜等变化。采用Western蛋白印迹从蛋白水平观察nephrin蛋白水平的表达。结果模型组大鼠镜下见肾小球体积增大,基底膜增厚(P<0.05)及系膜物质增多,足细胞与正常对照组比较明显减少(P<0.01),肾小球内可见散在炎细胞浸润。部分毛细血管腔受压变窄,部分肾小管上皮细胞胞浆疏松,轻度水肿。治疗组与模型组分别比较,肾小球基底膜未见明显增宽,足细胞数明显增加(P<0.05)。模型组大鼠血糖、24h尿蛋白、血肌酐水平明显升高,与对照组相比差异显著(P<0.05)。治疗组与模型组相比,上述生化指标均有所改善(P<0.05)。West-ern蛋白印迹结果表明,与正常组相比,模型组nephrin蛋白水平明显下降,经过厄贝沙坦干预后nephrin表达明显上调。结论厄贝沙坦能改善糖尿病肾病大鼠足细胞及肾脏的病理损害,显著减少糖尿病大鼠24h尿蛋白,上调nephrin的表达,具有一定的肾保护作用。
文摘目的研究骨化三醇对阿霉素(ADR)肾病大鼠肾组织损伤及足细胞裂隙隔膜分子(nephrin)表达的影响。方法6周龄雄性SD大鼠分为:正常对照组(Control组),ADR肾病组,骨化三醇治疗组(ADR+VD组)。大鼠模型以单次尾静脉注射阿霉素(7.5 mg/kg),治疗组大鼠灌胃法服用0.25μg/(kg·d)骨化三醇。所有大鼠在处死前称重、留尿检测24 h尿蛋白(UP),留血检测血清白蛋白(Alb)、尿素氮(BUN)、肌酐(Cre);苏木素-伊红(HE)染色、马松三色染色(Masson)、透射电镜(TEM)观察肾病理学结构;免疫荧光观察nephrin的定位;免疫组织化学染色半定量检测nephrin的表达;Western印迹检测nephrin蛋白表达。结果与ADR肾病组比,ADR+VD组24 h UP、BUN、Cre、肾脏指数显著降低(P<0.05),Alb水平显著升高(P<0.05);组织化学染色显示骨化三醇减轻肾组织系膜基质增生及纤维化;TEM显示骨化三醇修复足细胞损伤;免疫组化与Western印迹检测结果显示高度一致性,骨化三醇升高ADR引起的nephrin表达降低(P<0.05)。结论骨化三醇能够减轻ADR引起的肾损伤和大量蛋白尿,这与改善肾足细胞标记分子nephrin低表达密切相关。
基金Supported by the National Natural Science Foundation of China(No.30801504,30901926,81100530,81070590)The Sci-tech Project of Shaanxi Province(No.2012K19-04-01)
文摘OBJECTIVE:To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy,and the potential mechanism underpinned the action.METHODS:Forty adriamycin rats were randomly divided into two groups with the ratio of 1︰3;the small-number group served as control group(n=10),and the rats in the large-number group were treated with adriamycin to induce nephropathy;then they were further randomly assigned into 3subgroups:benazepril group(n=10),artemisiningroup(n=10),and adriamycin group(n=10).The benazepril group and artemisinin group were treated with benazepril suspl(5.0 mg/kg daily)and artemisinin suspl(150 mg/kg daily)respectively after being modeled;those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day.The treatment after model establishment lasted for a total of 4 weeks.The 24 h uric protein,blood biochemicals,renal pathological changes,renal ultrastrutural changes,Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay,completely automatic biochemical analyzer,light microscope,electron microscopy,Western blot and reverse transcription polymerase chain reaction,respectively.RESULTS:The rats in adriamycin group showed a significant increase in 24 h uric protein excretion,serum total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),serum creatinine(Scr)and decrease in albumin(Alb)(P<0.05 or P<0.01).Compared with adriamycin group,artemisinin could reduce uric protein excretion,decrease the serum TC,TG elevation,increase the serum Alb level,up-regulate the expressions of Nephrin and Podocin(P<0.05 or P<0.01),but no statistical significance effects on the levels of BUN,Scr in artemisinin group(P>0.05).The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats.CONCLUSION:Artemisinin might have an effe
