吡格列酮对2型糖尿病大鼠肾脏及nf κb mcp 1表达的影响-effect of pioglitazone on renal and nf κ b mcp 1 expression in type 2 diabetes rats.docxVIP

2.DM组和PIO组大鼠的TC和TG水平均明显高于NC组（P0.01），而PIO组的TC和TG水平较DM组明显降低（P0.01）。3.DM组和PIO组大鼠的NF-κB、SMCP-1水平和UMCP-1排泄率以及ACR、URBP排泄率和肾脏肥大指数均高于NC组（P0.01）；PIO组上述指标值较DM组均明显降低（P0.01）；且UMCP-1排泄率、SMCP-1、NF-κB分别与ACR、URBP排泄率及肾脏肥大指数呈正相关（P0.01）。4.肾组织免疫组化结果显示DM组和PIO组大鼠肾小球和肾小管MCP-1、NF-κB表达较NC组显著增强（P0.01），PIO组MCP-1、NF-κB表达较DM组有明显减弱（P0.01）。5.在光学显微镜下，NC组肾小球毛细血管腔无狭窄，肾小管-间质无炎症细胞浸润；DM组肾小球毛细血管袢塌陷，管腔闭塞，系膜区增宽，基膜增厚和系膜基质增多，肾小球体积增大，出现玻璃样变，肾小管肿胀、变性、空泡形成，肾间质可见大量淋巴细胞和单核巨噬细胞浸润。PIO组可见肾小球毛细血管管腔轻度狭窄，肾小管-间质见少量淋巴细胞浸润；6.第8周在透视电子显微镜下可见NC组肾小球基底膜（glomerularbasementmembrane,GBM）厚度均匀一致，未见足突（footprocesses，FP）融合；DM组GBM厚薄不均、结构模糊，FP广泛破坏和融合，足突融合率约达80%，系膜区基质增多，系膜区扩大，系膜细胞肿胀；PIO组的GBM无明显增厚，GBM的微结构相对规则，有少量FP融合，足突融合率约达30%，系膜区细胞轻度增生。结论肾组织局部炎症因子NF-κB、MCP-1表达增加与DN的发生发展密切相关，对糖尿病肾病诊断及评价其严重程度有一定的应用价值。盐酸吡格列酮可减少尿蛋白的排泄，抑制肾间质炎症细胞的浸润，提示具有肾脏保护作用。其可显著下调糖尿病大鼠肾组织局部NF-κB、MCP-1的过度表达、降低血NF-κB、MCP-1的浓度和尿MCP-1的排泄，这可能是吡格列酮具有抗炎作用而显示其对DN保护作用的重要机制之一。关键词糖尿病肾病；糖尿病；吡格列酮；核因子-κB；单核细胞趋化蛋白-1；大鼠EffectofPioglitazoneonRenalandNF-κB,MCP-lExpressioninType2DiabeticRats【Abstract】ObjectiveToobservetheeffectofpioglitzone(PIO)onmonocytechemoattractantprotein-1(MCP-1)andnuclearfactor-κB(NF-κB)level,therenalexpressionofNF-κBandMCP-1,renalconstitutionandfunctionandinvestigateitspossiblerenoprotectivemechanismsintype2diabetic(T2DM)rats.MethodThemodelofT2DMratwasestablishedbyfedwithhigh-sucrose-high-fatdietandinjectedlowdoseStreptozotocin(STZ)25mg/Kg,themodeloftheratswererandomlydividedintodiabetic(DMgroup)andpioglitazone(PIOgroup),comparedwiththenormalcontrolgroup(NCgroup)fedwithnormaldiet.ThentreatedwithpioglitazoneinterventioninPIOgroup.ThegroupPIOwastreatedwithpioglitazone10mg/Kg.dviaintragastricadministration,thegroupDMandNCweretreatedwithcorrespondingsodiumchloride.Thelevelofserummonocytechemoattractantprotein(SMCP-1),NF-κB,fastinginsulin(FINS),triglyceride(TG),cholesterol(TC),fastingperipheralbloodglucose(FBG),glycosylatedhemoglobinA1c(HbA1c),urinaryalbumin/creatinineratio(ACR),urinaryretinolbinding-protein(URBP),urinarymonocytechemoattractantprotein-1(UMCP-1)excretionr