根皮素对2型糖尿病肾病小鼠的肾保护作用及机制  

Renal-protection Effect and the Potential Mechanism of Phloretin in Mice with Type-2 Diabetic Nephropathy

作　　者：王兴红[1,2] 马永超 孙缦利[1,2] 李超敏 李海霞[3] WANG Xinghong;MA Yongchao;SUN Manli;LI Chaomin;LI Haixia(Luohe Medical College,Luohe 462000,China;Henan Special Medical Food Engineering Technology Research Center,Luohe 462000,China;The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]漯河医学高等专科学校,河南漯河462000 [2]河南省特医食品工程技术研究中心,河南漯河462000 [3]新疆医科大学第一附属医院,新疆乌鲁木齐830054

出　　处：《食品工业科技》2023年第11期418-426,共9页Science and Technology of Food Industry

基　　金：河南省高等学校重点科研项目(20B310007,22B550010);河南省重点研发与推广专项(科技攻关)项目(232102310501);河南省科技发展计划项目(科技攻关)(1721023610312);河南省高等学校青年骨干教师培养计划资助项目(2018GGJS258)。

摘　　要：为探究根皮素对2型糖尿病肾病小鼠肾损伤的分子保护作用及潜在机制,将小鼠随机分为正常对照组、糖尿病模型组、阳性药物组(二甲双胍500 mg/kg)、根皮素低、中、高剂量组(100、200、400 mg/kg·d)。造模成功后,各组小鼠灌胃给予相应药物,12周后,观察肾脏肥大指数、肾脏病理形态学变化,测定血尿素氮(BUN)、肌酐(Scr)和尿β2-微球蛋白(β2-MG)、血清白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)等指标,并检测肾组织丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-Px)活性和转录因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路相关蛋白表达。结果显示:与模型组比较,根皮素中、高剂量组小鼠肾脏肥大指数极显著减小(P<0.01);HE染色和Masson染色见肾小球体积明显减小、系膜增生明显减少,肾小球和肾间质纤维化明显减轻;血BUN、Scr、IL-1β、IL-18和肾组织MDA含量、α-平滑肌肌动蛋白(α-SMA)、胶原蛋白Ι(CollagenΙ)、NLRP3、IL-1β和Gasdermin D(GSDMD)蛋白表达显著降低(P<0.05或P<0.01);肾组织GSH-Px活性、Nrf2、HO-1、钙粘附蛋白-E(E-cadherin)蛋白表达显著升高(P<0.05)。结果表明:根皮素能保护2型糖尿病肾病小鼠肾功能改善肾纤维化,可能与调控Nrf2/HO-1/NLRP3通路改善氧化应激与炎症反应有关。To study the protective effect of phloretin against renal injury in mice with type-2 diabetic nephropathy and determine its potential mechanism at the molecular level,mice were randomized into a normal control group,diabetes model group,positive drug group(metformin,500 mg/kg),and low-,medium-,and high-dose phloretin groups(100,200,and 400 mg/kg·d,respectively).After successful modeling,mice in each group were administered the corresponding drugs via the intragastric route.Kidney hypertrophy index and renal pathomorphological changes were observed after 12 weeks.Blood urea nitrogen(BUN),serum creatinine(Scr),urineβ2-microglobulin,serum interleukin(IL)-1βand IL-18 levels were determined.Malondialdehyde(MDA)level,glutathione peroxidase(GSH-Px)activity,and nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)pathway-related protein expression in renal tissues were also determined.Compared with the model group,the medium-and high-dose phloretin groups showed a significant decrease in the kidney hypertrophy index of mice(P<0.01).An obvious reduction in glomerular volume was determined using Hematoxylin and Eosin staining and Masson staining,and a significant decrease in mesangial proliferation and an apparent alleviation in glomerular and renal interstitial fibrosis were noted.Significant reductions in BUN,Scr,IL-1β,and IL-18 levels in the blood,in MDA levels in renal tissues,and in the protein expression ofα-smooth muscle actin,Collagen I,NLRP3,IL-1β,and Gasdermin D were noted(P<0.05 or P<0.01).A significant increase in GSH-Px activity and in the expression of Nrf2,HO-1,and E-cadherin in renal tissues(P<0.05)was also founded.The results indicated that phloretin could protect renal function and alleviate renal fibrosis in mice with type-2 diabetic nephropathy.Its mechanism may be related to the regulation of the Nrf2/HO-1/NLRP3 pathway to improve oxidative stress and alleviate the inflammatory response.

关 键 词：糖尿病肾病 根皮素 转录因子 E2相关因子2/血红素加氧酶-1/核苷酸结合寡聚化结构域 样受体蛋白3通路 氧化应激 炎症 

分 类 号：TS201.4[轻工技术与工程—食品科学]