芍药苷减轻糖尿病小鼠肾组织炎症与JAK2/STAT3信号通路的关系  

Effect of paeoniflorin on preventing inflammation in diabetic mice kidneys and its relationship with JAK2/STAT3 signaling pathway

作　　者：李新玉[1] 邵云侠[1] 王坤[1] 吴永贵[1] Li Xinyu;Shao Yunxia;Wang Kun(Dept of Nephrology,The First Affiliated Hospital of Anhui Medical University,Hefei 23002)

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《安徽医科大学学报》2018年第7期1026-1032,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81374034)

摘　　要：目的研究芍药苷(PF)对糖尿病小鼠肾组织炎症的影响并初步探讨其可能的作用机制。方法 60只C57BL/6J小鼠随机分为5组:对照组、模型组、PF 25 mg/kg组、PF 50mg/kg组和PF 100 mg/kg组。于实验12周末测定各组小鼠血糖、相对肾重(肾重/体质量)及24 h尿白蛋白排泄率(UAER);光镜下观察各组小鼠肾组织病理学改变并评分;免疫组化检测肾组织CD68、p-JAK2及p-STAT3表达;Western blot检测肾组织p-JAK2、p-STAT3蛋白表达;实时定量PCR法检测肾组织肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、单核细胞趋化因子-1(MCP-1)与诱生型一氧化氮合酶(i NOS)的mRNA表达。结果实验12周末,模型组小鼠血糖、相对肾重、UAER及肾组织病理学评分较对照组明显升高(P<0.05,P<0.01),PF给药可使小鼠相对肾重、UAER及肾组织病理学评分较模型组明显减少(P<0.05,P<0.01)。与对照组相比,模型组小鼠肾组织CD68、p-JAK2、p-STAT3蛋白表达以及TNF-α、IL-1β、MCP-1和i NOS的mRNA表达均显著增加(P<0.01),PF 25、50、100 mg/kg给药组小鼠肾组织CD68、p-JAK2、p-STAT3蛋白表达以及TNF-α、IL-1β、MCP-1和i NOS的mRNA表达明显低于模型组(P<0.05,P<0.01)。结论 PF能够明显改善糖尿病小鼠肾损伤,这种保护作用的机制可能部分与抑制肾组织JAK2/STAT3信号通路激活及炎症反应有关。Objective To investigate the protective effect and possible mechanism of paeoniflorin（PF） on inflammation in diabetic mice kidneys.Methods 60 male C57 BL/6 J mice were randomly divided into five groups：normal control group,diabetic group,PF 25 mg/kg group,PF 50 mg/kg group and PF 100 mg/kg group.At 12 weeks,blood glucose,kidney weight/body weight,24 h urinary albumin excretion rate（UAER） were measured.Kidney pathological lesions and damage grade were detected by light microscopy.The expression of CD68,p-JAK2 and p-STAT3 were detected by immunohistochemistry.Western blot was used to detect the expression of p-JAK2 and p-STAT3 while tumor necrotic factor-α（TNF-α）,interleukin-1β（IL-1β）,monocyte chemoattractant protein-1（MCP-1） and inducible nitric oxide synthase（i NOS） mRNA level was evaluated by qRT-PCR.Results In week 12,compared with the control group,the levels of blood glucose,kidney weight/body weight,UAER level and kidney pathological lesions grade were higher in diabetic group（P0.05,P0.01）,while kidney weight/body weight,UAER level and kidney pathological lesions grade decreased significantly after PF intervention（P0.05,P0.01）.CD68,p-JAK2,p-STAT3 protein expression and TNF-α,IL1-β,MCP-1,i NOS mRNA expression were higher in diabetic group（P0.01） and lower in PF 25,50,100 mg/kg intervention groups（P0.05,P0.01）.Conclusion PF significantly improves diabetic nephropathy progression and these protective effects might associate with the inhibition of JAK2/STAT3 signaling pathway and inflammation.

关 键 词：糖尿病肾脏疾病 芍药苷 JAK2/STAT3信号通路 炎症 巨噬细胞 

分 类 号：R587.24[医药卫生—内分泌]