摘要
目的探讨芦荟苷对糖尿病肾病(DN)大鼠足细胞功能及尼克酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)/活性氧(ROS)/p38丝裂原活化蛋白激酶(p38 MAPK)信号通路的影响。方法高糖高脂饲料饲养大鼠4周,腹腔注射40 mg/kg STZ建立DN大鼠模型,随机分为模型组、阳性对照组、(低、中、高)剂量实验组;正常组大鼠不进行处理。阳性对照组灌胃9.45 mg/(kg·d)糖适平;(低、中、高)剂量实验组分别灌胃10、20、40 mg/(kg·d)芦荟苷,正常组、模型组灌胃等体积蒸馏水,连续6周。血糖仪检测空腹血糖水平;酶联免疫吸附(ELISA)检测血清中白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平;HE染色观察大鼠肾组织形态;超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)试剂盒检测肾组织中SOD、MDA、ROS水平;蛋白免疫印迹检测肾组织中NOX4、p38 MAPK、phospho-p38 MAPK、肾小球足细胞裂隙跨膜蛋白Nephrin、Podocin水平。结果给药前,与正常组相比,模型组、阳性对照组、(低、中、高)剂量实验组空腹血糖水平升高(P<0.05)。给药后,模型组肾组织肾小球肥大,系膜增厚和肾小球基底膜增厚,间质炎症浸润;(低、中)剂量实验组肾小球肥大现象逐渐缓解,肾小球系膜轻-中度增生,肾小管扩张减缓;高剂量实验组肾组织形态正常,结构清晰,肾小球、肾小管形态规则。与正常组相比,模型组空腹血糖,血清中IL-1β、TNF-α,肾组织中MDA、ROS,NOX4、phospho-p38 MAPK蛋白水平升高(P<0.05),肾组织中SOD水平、SOD/MDA,Nephrin、Podocin蛋白水平降低(P<0.05)。与模型组相比,阳性对照组、高剂量实验组空腹血糖,血清中IL-1β、TNF-α,肾组织中MDA、ROS,NOX4、phospho-p38 MAPK蛋白水平降低(P<0.05),肾组织中SOD水平、SOD/MDA,Nephrin、Podocin蛋白水平升高(P<0.05);中剂量实验组空腹血糖,血清中IL-1β、TNF-α,肾组织中MDA、ROS,NOX4蛋白水平降低(P<0.05),肾组织中SOD水平、SOD/MDA,Nephrin、Podocin蛋
Objective We investigated the effects of barbaloin on podocyte function and on the nicotinamide adenine dinucleotide phosphate oxidase 4(NEX4)/reactive oxygen species(ROS)/p38 mitogen activated protein kinase signaling pathway(p38 MAPK)in rats with diabetic nephropathy(DN).Methods The rats were fed high-sugar and high-fat diet for 4 weeks and injected 40 mg/kg STZ intraperitoneally establisha a DN rat model and randomly divided into a model group,a positive control group,dose dependent(low,medium,and high)experimental groups,and a normal group in which the rats were not treated.The positive control group was given 9.45 mg gliguidone per kilogram per day(kg·d)for six weeks.The low,medium,and high dose experimental groups were given 10,20,and 40 mg/(kg·d)barbaloin,respectively,by gavage for six weeks.The normal group and model group were given equal volume distilled water by gavage for six weeks.Fasting blood glucose levels were measured using a blood glucose meter,and the levels of interleukin-1β(IL-1β)and serum tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin and eosin(HE)staining was used to observe renal morphology.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in kidney tissue were detected using commercial SOD,MDA and ROS assay kits;and the levels of NADPH oxidase 4(NOX4),p38 mitogen-activated protein kinase(MAPK),phospho-p38 MAPK,the glomerular podocyte gap transmembrane protein Nephrin,and Podocin were detected by western blot.Results Before administration,compared with the normal group,the fasting blood glucose level of the model group,the positive control group,and the low,medium,and high dose experimental groups increased(P<0.05).After administration,glomerular hypertrophy,mesangial thickening,glomerular basement membrane thickening,and interstitial inflammatory infiltration were observed in the model group.In the low and middle dose group,glomerular hypertrophy was relieved gradually,the mesangial hype
作者
马冰沁
钱唯韵
罗振国
汪良芝
MA bingqin;QIAN Weiyun;LUO Zhenguo;WANG Liangzhi(General Medicine Department of Changzhou First People’s Hospital,Changzhou 213000,China)
出处
《中国比较医学杂志》
CAS
北大核心
2020年第9期1-7,共7页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金项目(81970627)。
