尿囊素对糖尿病肾病大鼠肾脏保护作用及机制探讨  

Protective effects and mechanism of allantoinon on renal injury of diabetic nephropathy rats

作　　者：赵耀 杨建华[1,2] 谯明 胡君萍[1] ZHAO Yao;YANG Jianhua;QIAO Ming;HU Junping(School of Pharmacy, Xinjiang Medical University, Urumqi 830011, China;Department of Pharmacy, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830011 [2]第一附属医院药学部,乌鲁木齐830054

出　　处：《新疆医科大学学报》2020年第8期1025-1030,共6页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区高技术研究发展计划项目(2019XS17105);新疆维吾尔自治区科技厅科技创新领军人才后备人选(2019XS14)。

摘　　要：目的研究尿囊素对高脂饮食联合链脲佐菌素(STZ)诱导的糖尿病肾病大鼠肾脏保护作用。方法取雄性SD大鼠75只建立2型糖尿病模型,将建模成功的SD大鼠随机分为模型组(生理盐水,1 mL/kg体质量)、尿囊素低、中、高(尿囊素200、400、800 mg/kg体质量),二甲双胍组(二甲双胍,200 mg/kg体质量)。每周称重和测定空腹血糖(FBG),第8周分笼收集各组大鼠24 h尿液,检测24 h尿蛋白含量。第8周末,处死大鼠,取血清检测血清肌酐(SCr)、尿素氮(BUN)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α),取肾组织匀浆液测定总超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA);HE染色观察大鼠肾脏病理改变;取肾皮质通过Western blot检测大鼠肾组织中转化生长因子β1(TGF-β1)、p38MAPK和Caspase-3的蛋白表达。结果与模型组比较,尿囊素低剂量组大鼠24 h尿量、24 h尿蛋白含量、FBG、SCr含量下降,SOD、GSH-PX活性升高,差异有统计学意义(P<0.05);尿囊素中、高剂量组大鼠24 h尿量、24 h尿蛋白含量下降,差异有统计学意义(P<0.01),肾脏指数、FBG、血清中SCr、BUN、IL-6、TNF-α、肾匀浆中MDA含量下降,SOD、GSH-PX活性升高,差异有统计学意义(P<0.01),CAT活性升高,差异有统计学意义(P<0.05),肾脏中p38MAPK、Caspase-3蛋白表达量降低,差异有统计学意义(P<0.01),TGF-β1蛋白表达量降低,差异有统计学意义(P<0.05)。结论尿囊素通过抑制凋亡信号通路因子的表达,减轻肾脏细胞凋亡,改善肾组织中氧化应激状态和炎症损伤,具有肾脏保护及延缓病程进展的作用。Objective To evaluate the effect of the allantoin in high fat diet/streptozotocin(HFD/STZ)induced diabetic nephropathy.MethodsA totalof 75 Sprague Dawley rats were fed with HFD for 6 weeks and then administered with 30 mg/kg STZ intraperitoneallyonce.Diabetic rats were treated with allantoin(200,400 and 800 mg/kg)and metformin(200 mg/kg)for 8 weeks.After the treatments,the blood,urine and kidney tissues were obtained for biochemical and histological analysis,the renal index was calculated.Serum samples were collected and tested for serum creatinine(SCr),urea nitrogen(BUN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),catalase(CAT),and malonaldehyde(MDA)levels were assessed in renal tissue that is to discuss the effect of allantoin on oxidative stress.Theprotein expressions of transforming growth factorβ1(TGF--β1),p38 mapk and Caspase-3 in the renal cortex weredetected byWestern blottingmethod.ResultsAllantoin markedly decreased blood glucose,Scr,BUN and urinary albumin levels in diabetic rats.Furthermore,allantoin upregulated renal antioxidant enzymes such as SOD,GSH,GSH-PX and CAT(P<0.05)and decreased MDA(P<0.05)in diabetic rats as well as reduced the levels of pro-inflammatory cytokines(IL-6,TNF-α)in diabetic rats(P<0.01).In addition,allantoin minimized the histological alterations in the kidney of diabetic rats.Allantoin resulted in a significant decrease in TGF-β1(P<0.05),p38MAPK and caspase-3(P<0.05)expression in the kidney of rats.ConclusionThis study sharply suggests that allantoin exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress,inflammation and apoptosis.

关 键 词：糖尿病肾病 尿囊素 氧化应激 炎症 TGF-β1/p38MAPK 

分 类 号：R285.5[医药卫生—中药学]