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目的:通过建立大鼠AP模型,并给予P物质受体拮抗剂L-703,606干预,探讨P物质及其受体在AP相关性肺损伤中的作用,探讨L-703,606对AP相关性肺损伤的治疗作用及机制。方法:选取Sprague-Dawley雄性大鼠54只,采用逆行胰胆管注射牛磺胆酸钠制备AP模型。随机分为假手术组(SO组)、AP组和L-703,606治疗组。各组设3、6和12 h三个亚组。进行肺组织病理学观察、肺湿/干重比率和肺组织MPO活力测定,应用免疫组化法测定肺组织P物质表达,应用western blot方法测定肺组织神经激肽受体-1(NK-1R)表达。结果:3、6和12 h各时间点,SO组病理学始终大致正常,肺湿/干重比率和肺组织MPO无明显差异,肺组织P物质和NK-1R少量表达。AP组均可见肺组织充血、水肿、出血、肺萎缩、肺不张和白细胞聚集,肺组织湿/干重比率增加,MPO活力增强,且随时间推移程度加重,肺组织P物质和NK-1R表达增强。与AP组相比,L-703,606组肺组织病理学改善,肺湿/干重比率、MPO活力均明显下降,肺组织P物质表达减弱,NK-1R表达无明显变化。结论:P物质在AP相关性肺损伤发病中发挥作用,L-703,606对AP相关性肺损伤具有一定保护作用,其机制可能与阻断P物质与其受体结合所介导的血管通透性增强以及中性粒细胞聚集、活化有关。
OBJECTIVE: To investigate the effect of substance P and its receptor on AP-related lung injury by establishing a rat model of AP and administering substance P antagonist L-703,606 to investigate the effect of L-703,606 on AP-related lung injury Therapeutic effect and mechanism. Methods: Fifty-four Sprague-Dawley rats were selected and AP model was induced by injecting sodium taurocholate into the pancreatic duct. Randomly divided into sham operation group (SO group), AP group and L-703,606 treatment group. Each group set 3, 6 and 12 h three subgroups. Lung tissue histopathology, lung wet / dry weight ratio and lung tissue MPO activity were measured. The expression of substance P in lung tissue was detected by immunohistochemistry. The expression of neurokinin receptor-1 (NK-1R )expression. Results: At 3, 6, and 12 h, the pathology of SO group was almost normal. There was no significant difference in lung wet / dry weight ratio and MPO in lung tissue between the time points of 3, 6 and 12 h. The expression of substance P and NK-1R in lung tissue was small. In AP group, lung tissue hyperemia, edema, hemorrhage, lung atrophy, atelectasis and leukocyte aggregation were observed. The ratio of wet / dry weight of lung tissue increased, MPO activity increased and the degree of lung injury increased with time. Enhanced expression. Compared with AP group, L-703,606 group had a significant improvement in lung histopathology, lung wet / dry weight ratio and MPO activity, and decreased P substance expression in lung tissue, while there was no significant change in NK-1R expression. CONCLUSION: Substance P plays a role in the pathogenesis of AP-related lung injury. L-703 and 606 have a protective effect on AP-related lung injury. The mechanism may be related to the enhancement of vascular permeability mediated by blockage of substance P and its receptor And neutrophil aggregation, activation related.