TLR4/NF-κBp65信号通路在重度急性胰腺炎大鼠急性肾损伤中作用的研究  

Effect of TLR4/NF-κBp65 Signaling Pathway on Acute Kidney Injury of Rats With Severe Acute Pancreatitis

作　　者：王彬[1] 吴晓尉[1] 李敏利[1] 郭美霞[1] 许小兵[1] 张晓华[1] 

机构地区：[1]南京军区南京总医院干部消化内科,210002

出　　处：《胃肠病学》2018年第2期78-82,共5页Chinese Journal of Gastroenterology

基　　金：军队保健专项科研课题(14BJZ28)

摘　　要：背景:TLR4/NF-κBp65信号通路在急性胰腺炎中起促炎作用,可调控炎症因子释放,但其在重度急性胰腺炎(SAP)合并急性肾损伤(AKI)炎症反应中的作用尚不明确。目的:探讨TLR4/NF-κBp65信号通路在实验性SAP合并AKI中的作用。方法:32只雄性Sprague-Dawley大鼠随机分为对照组和SAP 6 h、12 h、18 h组,每组8只。模型组大鼠以4%牛磺胆酸钠胰胆管逆行注射诱导SAP。动态测定血清肌酐(Cr)、尿素氮(BUN)水平,观察肾脏大体和组织病理学改变,ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,免疫组化法和蛋白质印迹法检测肾脏组织TLR4、NF-κBp65定位和表达。结果:与对照组相比,SAP组肾脏组织损伤随造模时间的延长逐渐加重,同时血清Cr、BUN和TNF-α、IL-6水平逐渐升高,肾脏组织TLR4、NF-κBp65表达逐渐增强(P均<0.05)。肾脏组织TLR4、NF-κBp65表达与血清Cr、BUN、TNF-α、IL-6水平均呈显著正相关。结论:在实验性SAP中,肾脏组织TLR4、NF-κBp65的表达变化与肾损伤严重程度和血清促炎细胞因子的变化相一致,提示TLR4/NF-κBp65信号通路在SAP合并AKI的病情进展中起重要促炎作用。Background: TLR4/NF-κBp65 signaling pathway plays an important role in triggering inflammatory response,and regulates releasing of cytokines in acute pancreatitis. However,the role of this pathway in inflammation in severe acute pancreatitis( SAP) associated with acute kidney injury( AKI) is not clear. Aims: To investigate the effect of TLR4/NF-κBp65 signaling pathway on AKI in experimental SAP. Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into 4 groups( 8 each) : normal control group,SAP 6 h,12 h,and 18 h groups. SAP was induced by retrograde injection of 4% sodium taurocholate into biliopancreatic duct. Serum levels of creatinine( Cr) and blood urea nitrogen( BUN) were measured dynamically. Pathological changes of kidney were observed macro-and microscopically. Serum levels of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6) were determined by ELISA,and the localization and expressions of TLR4 and NF-κBp65 in kidney were determined by immunohistochemical staining and Western blotting.Results: Compared with normal control group,the kidney injuries in SAP groups were gradually aggravated with disease progression; meanwhile,serum levels of Cr,BUN,TNF-α and IL-6 increased significantly,and the expressions of TLR4 and NF-κBp65 in kidney became more intensive( P all < 0. 05). Expressions of TLR4 and NF-κBp65 in kidney were positively correlated with the serum levels of Cr,BUN,TNF-α and IL-6. Conclusions: In experimental SAP,the changes of TLR4 and NF-κBp65 expressions in kidney are coincidence with the severity of kidney injury and the serum levels of proinflammatory cytokines,which indicates that TLR4/NF-κBp65 signaling pathway plays an important proinflammatory effect in disease progression of SAP associated with AKI.

关 键 词：TOLL样受体4 NF-ΚB 胰腺炎 急性坏死性 急性肾损伤 细胞因子类 

分 类 号：R576[医药卫生—消化系统]