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核因子-κB对哮喘大鼠气道重塑的影响。

Effect of nuclear factor-kappaB on airway remodeling in asthmatic rats.

作者信息

Xu Shuyun, Xu Yongjian, Zhang Zhenxiang, Ni Wang, Chen Shixin

机构信息

Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2004;24(1):13-8. doi: 10.1007/BF02830695.

Abstract

In order to investigate the effect of nuclear factor-kappaB (NF-kappaB) on airway remodeling in asthmatic rats, 18 Wistar rats were divided into three groups: asthmatic group; pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF-kappaB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF-kappaB activity and the expression of inhibitory protein kappaBalpha (I-kappaBalpha) in airway were detected by electrophoretic mobility shift assay (EMSA), Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up-regulation of airway NF-kappaB activity in asthmatic group, the number of goblet cells (3.084 +/- 0.86/100 microm basement membrane (BM)), the area of collagen (24.71 +/- 4.24 microm2/microm BM) and smooth muscle (13.81 +/- 2.11 microm2/microm BM) in airway were significantly increased (P<0.05) as compared with control group (0.14 +/- 0.05/100 microm BM, 14.31 +/- 3.16 microm2/microm BM and 7.67 +/- 2.35 microm2/microm BM respectively) and PDTC group (0.33 +/- 0.14/100 microm BM, 18.16 +/- 2.85 microm/microm BM and 8.95 +/- 2.16 microm2/microm BM respectively). However, there was no significant difference between PDTC group and control group (P>0.05). It was concluded that the activity of NF-kappaB is increased in airway of asthmatic rats. Inhibition of NF-kappaB activation can attenuate constructional changes in asthma airway, suggesting NF-kappaB may contribute to asthmatic airway remodeling.

摘要

为了研究核因子-κB(NF-κB)对哮喘大鼠气道重塑的影响,将18只Wistar大鼠分为三组:哮喘组;吡咯烷二硫代氨基甲酸盐(PDTC)组,该组大鼠在卵清蛋白(OVA)激发前腹腔注射NF-κB特异性抑制剂PDTC(100 mg/kg);对照组。分别采用电泳迁移率变动分析(EMSA)、蛋白质免疫印迹法(Western blot)和免疫组织化学法检测气道中NF-κB活性及抑制蛋白κBα(I-κBα)的表达。借助图像分析系统测量炎症细胞浸润、杯状细胞数量、气道中胶原和平滑肌面积。结果显示,与对照组(分别为0.14±0.05/100μm基底膜(BM)、14.31±3.16μm²/μm BM和7.67±2.35μm²/μm BM)及PDTC组(分别为0.33±0.14/100μm BM、18.16±2.85μm/μm BM和8.95±2.16μm²/μm BM)相比,哮喘组气道NF-κB活性上调,气道杯状细胞数量(3.084±0.86/100μm BM)、胶原面积(24.71±4.24μm²/μm BM)和平滑肌面积(13.81±2.11μm²/μm BM)显著增加(P<0.05)。然而,PDTC组与对照组之间无显著差异(P>0.05)。结论为哮喘大鼠气道中NF-κB活性增加。抑制NF-κB激活可减轻哮喘气道的结构改变,提示NF-κB可能参与哮喘气道重塑。

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