【作者】 郑旭锐；

【导师】 杨宇；

【作者基本信息】 成都中医药大学 ， 中医临床基础， 2011， 博士

【摘要】 目的：观察肺病(过敏性哮喘)模型大鼠对大肠的影响,探讨“肺病及肠”的病理变化及相关调控物质和ERK信号通路。方法：选用雄性Wistar大鼠,设空白组,肺病(过敏性哮喘)组共2组。除空白组外,肺病组采用腹部4点注射用1%卵白蛋白、氢氧化铝、生理盐水配制成的凝胶致敏剂,注射后超声雾化吸入1%OVA诱发哮喘。雾化一周后检测动物肺功能；收集支气管肺泡灌洗液及粪便检测肺肠微生态；采集动物股动脉血液检测血常规和TNF-α、IL-1含量；光镜观察肺、胃、十二指肠、空肠、回肠、结肠、直肠组织病理变化；电镜观察肺和结肠组织；免疫组化法检测肺、胃、十二指肠、空肠、回肠、结肠、直肠组织中CCK8、CGRP、SP、VIP含量；RT-PCR法检测肺、结肠组织iNOS、ERKmRNA表达。结果：1.病理生理肺功能：肺病组大鼠的呼吸频率明显增快,潮气量、每分钟通气量明显降低,与空白组比较有显著性差异(P<0.01)；粪便性状、质地、干湿重量观察：肺病组大鼠大便次数减少,排便较空白组困难,粪便的外观变小,质地干硬,粒数减少、干湿重量均减轻(P<0.05)；胃排空与肠推进试验：与空白组比较,肺病组大鼠胃内残留率升高(P<0.05),大肠炭末推进率降低(P<0.05)；肺肠微生态：肺病组的肺部需氧菌、真菌明显增多,厌氧菌显著减少(P)<0.01)；肠道需氧菌、真菌、大肠杆菌较空白组显著增多(P<0.01),厌氧菌、类杆菌和双歧杆菌显著减少(P<0.01)；2.病理形态光镜、电镜观察：光镜观察结果显示造模前后大鼠肺和结肠组织出现一定程度的病理改变,而十二指肠、空肠、回肠、直肠、胃组织无明显变化；电镜观察结果显示肺和结肠组织出现一定程度的病理改变。3.相关调控物质CCK8、CGRP、SP、VIP含量变化：肺病组肺组织CCK8含量减少、CGRP含量增多、SP含量增多、VIP含量减少,与空白组比较有统计学差异(P<0.01)；结肠组织CCK8含量增多、CGRP含量增多、SP含量减少、VIP含量增多,与空白组比较有统计学差异(P<0.01或P<0.05)；两组的十二指肠、空肠、回肠、直肠、胃等组织中CCK8、CGRP、SP、CIP的含量变化比较无统计学差异(P>0.05)TNF-α、IL-1:肺病组血清TNF-α、IL-1明显升高,与空白组比较有显著性差异(P<0.01)；iNOSmRNA表达：肺病组大鼠的肺组织、结肠组织iNOS mRNA表达升高,与空白组比较有显著性差异(P<0.01)。ERKmRNA表达：肺病组大鼠的肺、结肠组织ERKmRNA表达升高,与空白组比较有差异(P＜0.01或P<0.05)。结论：1.肺在一定的病理状态下可以影响及大肠,出现大肠的病理变化。2.肺在一定的病理状态下可以影响及大肠,出现大肠的相关调控物质变化。3.肺在一定的病理状态下可以影响及大肠,出现大肠的ERKmRNA表达的变化。4. CCK8、CGRP、SP、VIP、TNF-α、IL-1、iNOS可能是“肺病及肠”的物质基础。更多还原

【Abstract】 Objective:Observed pulmonary disease (allergic asthma) the impact of the large intestine in rats to explore the "lung and intestinal" mechanisms of pathological changes and related control material and ERK signaling pathways.Methods:Male Wistar rats were used, a blank group, lung (allergic asthma) group 2 group. In addition to the control group, the lung disease group with 4 points abdominal injection with 1% egg albumin, aluminum hydroxide, saline gel preparation of sensitization, after injection of 1% OVA inhalation ultrasound induced asthma. Pulmonary function test animals a week after atomization; collection of bronchoalveolar lavage fluid and lung intestinal microflora stool; collecting animals and femoral artery blood test blood TNF-α, IL-1; light microscopy lung, stomach, duodenum, Jejunum, ileum, colon, rectum pathologic changes; electron microscopy of lung and colon; immunohistochemistry lung, stomach, duodenum, jejunum, ileum, colon, rectum tissue CCK8, CGRP, SP, VIP Content; RT-PCR detection of lung, colon tissue iNOS, ERK mRNA expression.Results:1. PathophysiologyLung functions:lung disease group were significantly increased respiratory frequency, tidal volume, minute ventilation decreased significantly compared with the control group significantly (P＜0.01);Stool, texture, wet and dry weight observed:lung solution will reduce the number of rats, defecation difficult than the control group, the appearance of feces smaller, dry and hard texture, grain number reduction, reducing both wet and dry weight (P＜0.05);Gastric emptying and intestinal propulsion test:compared with the control group, lung rats increased gastric residual rate (P＜0.05), the end of the colon promote the rate of carbon reduction (P＜0.05);Pulmonary intestinal microflora:aerobic pulmonary tuberculosis group, fungi increased significantly, anaerobic bacteria were significantly reduced (P＜0.01); intestinal aerobic bacteria, fungi, E. coli was significantly increased compared with the control group (P＜0.01), And anaerobes, Bacteroides and Bifidobacterium were significantly reduced (P＜0.01);Morphological observations:Light microscopy showed that the modeling rat lung and colon before and after a certain pathological changes, and the duodenum, jejunum, ileum, rectum, no significant changes in gastric tissue; electron microscope showed that the lung and colon Pathological changes of a certain organization.2. The relevant regulatorsSP, VIP, CGRP, CCK8 content:content of lung reduction in lung tissue CCK8, CGRP levels increased, SP content increased, VIP content decreased, compared with the control group were significantly different (P＜0.01), colon CCK8 content increased, Increased CGRP content, SP content decreased, VIP content increased, compared with the control group were significantly different (P＜0.01 or P＜0.05), while the two groups of duodenum, jejunum, ileum, rectum and stomach the expression of VIP No significant difference between the amount (P> 0.05)TNF-α, IL-1:lung serum TNF-α, IL-1 significantly increased compared with the control group significantly (P＜0.01);iNOS mRNA expression:lung tissue of rats lung and colon tissue expression of iNOS mRNA increased compared with the control group significantly (P＜0.01).ERK mRNA expression:pulmonary disease rats lung, colon ERK mRNA increased expression differences compared with the control group (P＜0.01 or P＜0.05).Conclusion:1. Lung under certain pathological conditions and can affect the colon, colonic pathological changes occur.2. Lung under certain pathological conditions and can affect the large intestine, large intestine appears related to changes in regulation of substances.3. Lung under certain pathological conditions and can affect the colon, there ERK mRNA expression in the large intestine.4. CCK8, CGRP, SP, VIP, TNF-α, IL-1, iNOS may be a "lung and intestine, "the material basis.更多还原