白皮杉醇对DN大鼠肾小球内皮细胞损伤的保护作用及其机制  

Protective effect of piceatannol on endothelial cell injury rats with diabetic nephropathy

作　　者：张云霞[1] 邱书娟 孙秀菊[1] 郭振涛[1] 郭民[1] ZHANG Yunxia;QIU Shujuan;SUN Xiuju;GUO Zhentao;GUO Min(Affiliated Hospital of Weifang Medical University, Weifang 261031, China)

机构地区：[1]潍坊医学院附属医院,山东潍坊261031

出　　处：《山东医药》2018年第44期42-46,共5页Shandong Medical Journal

摘　　要：目的探讨白皮杉醇(PIC)对糖尿病肾病(DN)大鼠肾小球内皮细胞损伤的保护作用及其机制。方法选择雄性SD大鼠50只,随机分为对照组、模型组及PIC低、中、高剂量组,每组10只。模型组及PIC低、中、高剂量组高糖高脂饲料喂养4周,给予链脲佐菌素(STZ) 30 mg/kg一次性腹腔注射,制备DN模型。腹腔注射次日,PIC低、中、高剂量组分别给予PIC 50、100、200 mg/(kg·d)灌胃,模型组给予等量生理盐水灌胃,连续灌胃12周。对照组普通饲料喂养,不予注射STZ,同期等量生理盐水灌胃。各组灌胃12周,检测空腹血糖(FPG)、血肌酐(Scr)、胱抑素C(Cys-C)及24 h尿白蛋白(U-Alb);取部分肾组织,制成10%组织匀浆,离心留取上清液,检测上清液内皮素1(ET-1)、血管内皮生长因子(VEGF)、NO及超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量;取部分肾皮质,PAS染色,观察肾小球、肾小管、系膜基质病理形态及炎性细胞浸润情况;分别采用RT-PCR法和免疫组化法检测肾组织p38丝裂原活化蛋白激酶(p38 MAPK)、TNF-αmRNA和蛋白表达。结果模型组FPG、Scr、Cys-C、U-Alb均明显高于对照组,肾组织NO水平、SOD活性均明显低于对照组,ET-1、VEGF水平及MDA含量均明显高于对照组(P均<0. 05);模型组肾组织出现明显损伤,而对照组肾组织未见明显异常。除Scr外,PIC各组上述指标均有明显改善,且随着PIC浓度升高,其效果越来越明显(P均<0. 05)。模型组肾组织p38 MAPK、TNF-α表达均明显高于对照组(P均<0. 05)。PIC各组肾组织p38 MAPK、TNF-α表达均明显低于模型组,且随着PIC浓度升高,其效果越来越明显(P均<0. 05)。结论 PIC能剂量依赖性地减轻肾小球内皮细胞损伤,保护肾功能,延缓DN进展,其作用机制可能与抑制p38 MAPK通路活化,减轻炎症反应、缓解氧化应激反应有关。Objective To investigate the effect and mechanism of piceatannol(PIC)on endothelial cell injury rats with diabetic nephropathy(DN).Methods Fifty male SD rats were randomly divided into the control group,model group,and low-dose,medium-dose and high-dose PIC groups,with10in each group.Rats in the model group and PIC groups were fed with high-glucose and high-fat diet for4weeks.The DN models were established by intraperitoneal injection of30mg/kg STZ.On the next day after intraperitoneal injection,PIC50,100,and 200mg/(kg·d)was given to the rats of the low-dose,medium-dose and high-dose PIC groups,and the same amount of saline was given to the rats of the model group for12weeks.The rats in the control group were fed with normal diet,and the same amount of saline was intragastrically perfused without STZ injection.Fasting blood glucose(FPG),serum creatinine(Scr),cystatin C(Cys-C)and24h urinary albumin(U-Alb)were measured in each group after12weeks of perfusion;10%tissue homogenate was made from renal tissue.The supernatant was collected after centrifugation for the detection of endothelin-1(ET-1),vascular endothelial growth factor(VEGF),NO,the activity of SOD and MDA;glomeruli,renal tubules,mesangial matrix and the infiltration of inflammatory cells was observed by PAS staining;the expression of p38mitogen-activated protein kinase(p38MAPK),TNF-αmRNA and protein in the renal tissues was detected by RT-PCR and immunohistochemistry,respectively.Results FPG,Scr,Cys-C,U-Alb,ET-1,VEGF level and MDA content in the model group were significantly higher than those in the control group,while NO level and SOD activity in the renal tissues were significantly lower than those in the control group(all P<0.05);the model group showed significant renal injury,while the control group showed no obvious abnormality.The above indexes in all PIC groups were obviously improved except for Scr,and with the increase of PIC concentration,the effect was more and more obvious(all P<0.05).The expression of p38MAPK and TNF-αin the model group w

关 键 词：糖尿病肾病 白皮杉醇 内皮细胞功能 P38丝裂原活化蛋白激酶 

分 类 号：R587.1[医药卫生—内分泌]