西维来司钠对急性百草枯中毒大鼠治疗作用研究
发布时间：2019-04-04 16:55
【摘要】：[研究目的] 分析急性百草枯中毒大鼠相关炎性因子和纤维化因子的动态变化规律,探讨西维来司钠对大鼠早期急性肺损伤及肺部纤维化病变的拮抗治疗作用。 [研究方法] 128只Wistar大鼠,雌雄各半,随机分为4组。A组：高剂量治疗组,B组：低剂量治疗组,C组：模型对照组,D组：空白对照组。采用经口染毒方式(50mg/kg)建立APQ大鼠模型,分别给予A、B组8mg/kg、3mg/kg的Sivelestat Sodium腹腔注射治疗,C、D组给予生理盐水。在1、3、7、21d时间点收集大鼠外周血,大鼠处死后分离肺组织制作大鼠肺组织HE染色切片,光镜下观察组织形态改变。运用酶联免疫法(ELISA)检测各时间点大鼠血清及肺组织匀浆中的肿瘤坏死因子-α (TNF-α)、白介素-8(IL-8)、中性粒细胞弹性蛋白酶(NE)、转化生长因子-β1(TGF-β1)表达水平。 [研究结果] 1急性百草枯中毒大鼠炎性因子变化的实验研究 1.1大鼠肺组织病理学改变 NS组肺组织结构基本正常。APQ组大鼠肺组织肉眼观察呈苍白色,光镜下观察,APQ组大鼠的肺组织在第1天可见少量的巨噬细胞浸润,至第3天,视野中巨噬细胞开始大量增加,并出现少量的多行核白细胞,模型组较NS组数量明显增多。第7天,炎性细胞数量达到最大,中性粒细胞大量聚集,视野中开始出现少量的成纤维细胞。肺泡之间的间隔明显变宽,炎性细胞大量聚集浸润,呈典型的弥漫性肺泡炎。在实验室的第21天,镜下观察APQ组可见大量成纤维细胞。第21天较第7天炎性细胞大量减少,但是与NS组比较,仍未恢复到正常水平。 1.2大鼠肺组织匀浆、血清中炎性因子表达水平的动态变化 (1)相关研究因子在各个时间点(除第3天外),模型组大鼠中的表达水平均明显高于NS组,并且差异具有统计学意义(P0.05)。 (2)每个剂量组内,TNF-α、IL-8、NE、TGF-β1表达水平在第1天到第7天均见明显升高,至21天,指标水平开始出现下降,各时间点之间TNF-α、IL-8、 NE具有统计学差异性。 2西维来司钠在急性百草枯中毒大鼠中的拮抗作用 2.1大鼠肺组织病理学改变 模型组大鼠肺组织肉眼下观察呈苍白色。光镜下观察,模型组大鼠肺组织在第1天可见肺泡壁和肺泡间隔毛细血管旁中性粒细胞轻度浸润,靠近终末气道的肺泡壁和肺泡间隔有少量巨噬细胞浸润；至第3天,巨噬细胞大量增加并出现聚集,出现了肺泡炎特征,可见大量的中性粒细胞渗出。第7天,部分支气管上皮细胞及肺泡上皮细胞脱落,肺泡间隔增宽且出现了水肿,可见较多的中性粒细胞、巨噬细胞在肺泡腔内聚集。至21天,镜下观察模型组可见肺泡腔大部分消失,肺泡间隔断裂,细胞结节数量多,炎性细胞主要是淋巴细胞和浆细胞,偶尔可以见到成纤维细胞。高低剂量组内,第21天较第7天炎性细胞大量减少,其中干预组的炎性细胞数量明显少于模型组,但是与空白对照组比较,仍未恢复到正常水平。 2.2大鼠肺组织匀浆、血清中炎性因子表达水平的动态变化 (1)按照各剂量组比较,相关因子在模型组中的表达水平均明显高于高低剂量组,与高剂量组比较,差异具有统计学意义(P0.05)。TGF-β1因子表达水平在模型组中表达水平略有升高,但无统计学差异。 (2)每个剂量组内,TNF-α、IL-8、NE、TGF-β1表达水平在第1天到第7天均见明显升高,至21天,指标水平出现下降,各时间点之间TNF-α、IL-8、NE具有统计学差异性。 [研究结论] 1大鼠染毒后1-21天内,肺组织病理学改变为早期的炎症反应,表现为巨噬细胞及中心粒细胞的浸润聚集,后期的肺泡间隔明显增厚,成纤维细胞出现,纤维组织开始增生,肺泡正常组织发生变化,炎性因子在炎症反应过程中发挥作用。 2染毒大鼠肺组织匀浆和血清中的炎性因子水平随时间先升高后降低,并与肺组织病理变化一致,可作为反应APQ大鼠肺炎症及纤维化进程的敏感指标。 3西维来司钠干预大鼠的炎性因子检测水平明显低于模型对照组,变化与肺组织病理一致,表明了西维来司钠在百草枯致ALI的治疗中可以对炎性病变起到一定的拮抗作用。 4西维来司钠干预组大鼠肺组织的TGF-β1因子未检测到与对照组存在显著性差异,提示西维来司钠对于大鼠肺纤维化的拮抗作用需要进一步研究探讨。
[Abstract]:[Study Purpose] The changes of relevant inflammatory factors and fibrosis factors in rats with acute paraquat poisoning were analyzed, and the treatment of acute lung injury and pulmonary fibrosis in rats with early acute lung injury and pulmonary fibrosis were discussed. to be used [Methods] 128 Wistar rats were male and female respectively. The machine was divided into 4 groups. Group A: high-dose treatment group, group B: low-dose treatment group, group C: model control group and group D: In the control group, an APQ rat model was established by oral exposure (50 mg/ kg), and the group A and group B were given 8 mg/ kg and 3 mg/ kg of Sivelestat S. The peripheral blood of the rat was collected at 1,3,7, and 21 days, and the rats were separated from the lung tissue after being sacrificed to make the HE-stained section of the lung tissue of the rat, and the group was observed under the light microscope. The expression of tumor necrosis factor-1 (TNF-1), interleukin-8 (IL-8), neutrophil elastase (NE), and transformation growth factor-1 (TGF-1 1) in serum and lung tissue of rats were detected by enzyme-linked immunosorbent assay (ELISA). ) Expression level. [Study result] 1 Acute paraquat poisoning rat experimental study on the change of sex factor 1 .1 Pathological changes of lung tissue in rats The lung tissue structure of the NS group was basically normal. The visual observation of the lung tissue in the APQ group was pale and white, and the lung tissues of the APQ group in the APQ group showed a small amount of macrophage infiltration on the first day, and the macrophages in the field of view started to increase in a large amount on the third day. and a small number of multi-line nuclear leukocytes, The number of inflammatory cells increased significantly in the model group than in the NS group. There was a small amount of fibroblasts at the beginning. The space between the alveoli was significantly widened and the inflammatory cells gathered in a large amount. Infiltrating, typical of diffuse alveolitis. On day 21 of the laboratory, microscopic observations A large number of fibroblasts were visible in the APQ group. The inflammatory cells in the first day of day 21 were significantly reduced, but compared with NS in group comparison, that normal level was not recovered. 1.2 rat lung tissue homogenate, The dynamic changes of the expression level of inflammatory factors in the serum (1) were significantly higher in the model group than in the NS group at each time point (except for the third day), and the expression level of the model group in the model group was significantly higher than that of the NS group. (2) The expression level of TNF-1, IL-8, NE and TGF-1 in each dose group was significantly increased from day 1 to day 7. There was a statistical difference between F-1, IL-8 and NE. 2-Siwei's sodium in acute paraquat Antagonism in toxic rats: 2.1 rat lung group In the model group, the lung tissue of the model group was observed to be pale and white with the naked eye. Under the light microscope, the lung tissue of the model group was seen to have slight infiltration of the neutrophil in the alveolar wall and the alveolar space at the first day, and a small amount of the alveolar wall and the alveolar space near the terminal airway were small. Macrophage infiltration; on Day 3, the macrophages increased in large numbers and out At present, there is an alveolitis characterized by a large number of neutrophils. On day 7, some of the bronchial epithelial cells and the alveolar epithelial cells come off and the alveolar space is widened and appears. Edema, more of the neutrophils and macrophages were collected in the alveolar space. To 21 days, the most of the alveolar cavity disappeared, the alveolar space was broken, the number of cell nodules was large, the inflammation was inflammatory, The cells were mainly lymphocytes and plasma cells, and the fibroblasts were occasionally seen. In the high and low dose group, the inflammatory cells in the first day of the day 21 were significantly reduced, and the number of inflammatory cells in the intervention group was significantly less. In the model group, the normal level was not recovered compared to the blank control group. 2.2 The dynamic changes (1) of the expression level of inflammatory factors in the rat lung tissue and serum were compared with each dose group. The expression level of the sub-group in the model group was significantly higher than that of the high and low dose group, and the difference was statistically significant compared with the high-dose group (P0.05). In each dose group, the expression level of TNF-1, IL-8, NE, TGF-1 1 in the model group increased slightly, and the expression level of TNF-1, IL-8, NE, TGF-1 1 in each dose group was significantly increased from day 1 to day 7, and the level of the index was higher in 21 days. Now fall, each time There was a significant difference in TNF-1, IL-8, and NE between the interstitial sites.[Conclusion] 1-21 days after the rat's exposure, the pathological changes of the lung tissue were the early inflammatory reaction, which showed that the macrophages and the central granules were fine. the infiltration and aggregation of the cells, the alveolar space at the later stage are obviously thickened, the fibroblasts appear, the fibers In that course of the inflammatory reaction, the level of inflammatory factor in the homogenate and serum of the lung tissue of the rat was decreased with the increase of time. And the level of inflammatory factor in the rats was significantly lower than that of the control group and the pathological changes of the lung. It was found that the TGF-1 factor in the lung tissue of the rats with the sodium intervention group was not detected.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R595.4
本文编号：2453996
[Abstract]:[Study Purpose] The changes of relevant inflammatory factors and fibrosis factors in rats with acute paraquat poisoning were analyzed, and the treatment of acute lung injury and pulmonary fibrosis in rats with early acute lung injury and pulmonary fibrosis were discussed. to be used [Methods] 128 Wistar rats were male and female respectively. The machine was divided into 4 groups. Group A: high-dose treatment group, group B: low-dose treatment group, group C: model control group and group D: In the control group, an APQ rat model was established by oral exposure (50 mg/ kg), and the group A and group B were given 8 mg/ kg and 3 mg/ kg of Sivelestat S. The peripheral blood of the rat was collected at 1,3,7, and 21 days, and the rats were separated from the lung tissue after being sacrificed to make the HE-stained section of the lung tissue of the rat, and the group was observed under the light microscope. The expression of tumor necrosis factor-1 (TNF-1), interleukin-8 (IL-8), neutrophil elastase (NE), and transformation growth factor-1 (TGF-1 1) in serum and lung tissue of rats were detected by enzyme-linked immunosorbent assay (ELISA). ) Expression level. [Study result] 1 Acute paraquat poisoning rat experimental study on the change of sex factor 1 .1 Pathological changes of lung tissue in rats The lung tissue structure of the NS group was basically normal. The visual observation of the lung tissue in the APQ group was pale and white, and the lung tissues of the APQ group in the APQ group showed a small amount of macrophage infiltration on the first day, and the macrophages in the field of view started to increase in a large amount on the third day. and a small number of multi-line nuclear leukocytes, The number of inflammatory cells increased significantly in the model group than in the NS group. There was a small amount of fibroblasts at the beginning. The space between the alveoli was significantly widened and the inflammatory cells gathered in a large amount. Infiltrating, typical of diffuse alveolitis. On day 21 of the laboratory, microscopic observations A large number of fibroblasts were visible in the APQ group. The inflammatory cells in the first day of day 21 were significantly reduced, but compared with NS in group comparison, that normal level was not recovered. 1.2 rat lung tissue homogenate, The dynamic changes of the expression level of inflammatory factors in the serum (1) were significantly higher in the model group than in the NS group at each time point (except for the third day), and the expression level of the model group in the model group was significantly higher than that of the NS group. (2) The expression level of TNF-1, IL-8, NE and TGF-1 in each dose group was significantly increased from day 1 to day 7. There was a statistical difference between F-1, IL-8 and NE. 2-Siwei's sodium in acute paraquat Antagonism in toxic rats: 2.1 rat lung group In the model group, the lung tissue of the model group was observed to be pale and white with the naked eye. Under the light microscope, the lung tissue of the model group was seen to have slight infiltration of the neutrophil in the alveolar wall and the alveolar space at the first day, and a small amount of the alveolar wall and the alveolar space near the terminal airway were small. Macrophage infiltration; on Day 3, the macrophages increased in large numbers and out At present, there is an alveolitis characterized by a large number of neutrophils. On day 7, some of the bronchial epithelial cells and the alveolar epithelial cells come off and the alveolar space is widened and appears. Edema, more of the neutrophils and macrophages were collected in the alveolar space. To 21 days, the most of the alveolar cavity disappeared, the alveolar space was broken, the number of cell nodules was large, the inflammation was inflammatory, The cells were mainly lymphocytes and plasma cells, and the fibroblasts were occasionally seen. In the high and low dose group, the inflammatory cells in the first day of the day 21 were significantly reduced, and the number of inflammatory cells in the intervention group was significantly less. In the model group, the normal level was not recovered compared to the blank control group. 2.2 The dynamic changes (1) of the expression level of inflammatory factors in the rat lung tissue and serum were compared with each dose group. The expression level of the sub-group in the model group was significantly higher than that of the high and low dose group, and the difference was statistically significant compared with the high-dose group (P0.05). In each dose group, the expression level of TNF-1, IL-8, NE, TGF-1 1 in the model group increased slightly, and the expression level of TNF-1, IL-8, NE, TGF-1 1 in each dose group was significantly increased from day 1 to day 7, and the level of the index was higher in 21 days. Now fall, each time There was a significant difference in TNF-1, IL-8, and NE between the interstitial sites.[Conclusion] 1-21 days after the rat's exposure, the pathological changes of the lung tissue were the early inflammatory reaction, which showed that the macrophages and the central granules were fine. the infiltration and aggregation of the cells, the alveolar space at the later stage are obviously thickened, the fibroblasts appear, the fibers In that course of the inflammatory reaction, the level of inflammatory factor in the homogenate and serum of the lung tissue of the rat was decreased with the increase of time. And the level of inflammatory factor in the rats was significantly lower than that of the control group and the pathological changes of the lung. It was found that the TGF-1 factor in the lung tissue of the rats with the sodium intervention group was not detected.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R595.4
【参考文献】
相关期刊论文 前7条
1 王殿华,刘旭,凌亦凌;中性粒细胞弹性蛋白酶与急性肺损伤[J];国外医学.呼吸系统分册;2004年06期
2 吴丽红;李艳辉;;百草枯中毒发病机制的研究进展[J];中华急诊医学杂志;2007年05期
3 魏晓为;李宁;朱维铭;;肿瘤坏死因子受体与炎性肠病发病机制研究进展[J];医学研究生学报;2009年04期
4 张建新;郭平选;;乌司他丁对急腹症患者围术期肿瘤坏死因子及白介素的影响[J];山东医药;2008年10期
5 徐伟;谈永飞;蒋国军;葛志军;王国祥;;雾化吸入氟化碳对急性肺损伤大鼠肺表面活性物质及其相关蛋白-A和TNF-α的影响[J];江苏医药;2010年03期
6 高冬娜;张_g;;急性肺损伤研究进展[J];中国急救医学;2008年01期
7 高冬娜;张_g;;中性粒细胞弹性蛋白酶致急性肺损伤机制的研究进展[J];中国危重病急救医学;2006年08期
，本文编号：2453996
本文链接：https://www.wllwen.com/yixuelunwen/jjyx/2453996.html
最近更新
教材专著
