西維來司鈉對急性百草枯中毒大鼠治療作用研究
發(fā)布時(shí)間：2019-04-04 16:55
【摘要】：[研究目的] 分析急性百草枯中毒大鼠相關(guān)炎性因子和纖維化因子的動態(tài)變化規(guī)律,探討西維來司鈉對大鼠早期急性肺損傷及肺部纖維化病變的拮抗治療作用。 [研究方法] 128只Wistar大鼠,雌雄各半,隨機(jī)分為4組。A組：高劑量治療組,B組：低劑量治療組,C組：模型對照組,D組：空白對照組。采用經(jīng)口染毒方式(50mg/kg)建立APQ大鼠模型,分別給予A、B組8mg/kg、3mg/kg的Sivelestat Sodium腹腔注射治療,C、D組給予生理鹽水。在1、3、7、21d時(shí)間點(diǎn)收集大鼠外周血,大鼠處死后分離肺組織制作大鼠肺組織HE染色切片,光鏡下觀察組織形態(tài)改變。運(yùn)用酶聯(lián)免疫法(ELISA)檢測各時(shí)間點(diǎn)大鼠血清及肺組織勻漿中的腫瘤壞死因子-α (TNF-α)、白介素-8(IL-8)、中性粒細(xì)胞彈性蛋白酶(NE)、轉(zhuǎn)化生長因子-β1(TGF-β1)表達(dá)水平。 [研究結(jié)果] 1急性百草枯中毒大鼠炎性因子變化的實(shí)驗(yàn)研究 1.1大鼠肺組織病理學(xué)改變 NS組肺組織結(jié)構(gòu)基本正常。APQ組大鼠肺組織肉眼觀察呈蒼白色,光鏡下觀察,APQ組大鼠的肺組織在第1天可見少量的巨噬細(xì)胞浸潤,至第3天,視野中巨噬細(xì)胞開始大量增加,并出現(xiàn)少量的多行核白細(xì)胞,模型組較NS組數(shù)量明顯增多。第7天,炎性細(xì)胞數(shù)量達(dá)到最大,中性粒細(xì)胞大量聚集,視野中開始出現(xiàn)少量的成纖維細(xì)胞。肺泡之間的間隔明顯變寬,炎性細(xì)胞大量聚集浸潤,呈典型的彌漫性肺泡炎。在實(shí)驗(yàn)室的第21天,鏡下觀察APQ組可見大量成纖維細(xì)胞。第21天較第7天炎性細(xì)胞大量減少,但是與NS組比較,仍未恢復(fù)到正常水平。 1.2大鼠肺組織勻漿、血清中炎性因子表達(dá)水平的動態(tài)變化 (1)相關(guān)研究因子在各個(gè)時(shí)間點(diǎn)(除第3天外),模型組大鼠中的表達(dá)水平均明顯高于NS組,并且差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。 (2)每個(gè)劑量組內(nèi),TNF-α、IL-8、NE、TGF-β1表達(dá)水平在第1天到第7天均見明顯升高,至21天,指標(biāo)水平開始出現(xiàn)下降,各時(shí)間點(diǎn)之間TNF-α、IL-8、 NE具有統(tǒng)計(jì)學(xué)差異性。 2西維來司鈉在急性百草枯中毒大鼠中的拮抗作用 2.1大鼠肺組織病理學(xué)改變 模型組大鼠肺組織肉眼下觀察呈蒼白色。光鏡下觀察,模型組大鼠肺組織在第1天可見肺泡壁和肺泡間隔毛細(xì)血管旁中性粒細(xì)胞輕度浸潤,靠近終末氣道的肺泡壁和肺泡間隔有少量巨噬細(xì)胞浸潤；至第3天,巨噬細(xì)胞大量增加并出現(xiàn)聚集,出現(xiàn)了肺泡炎特征,可見大量的中性粒細(xì)胞滲出。第7天,部分支氣管上皮細(xì)胞及肺泡上皮細(xì)胞脫落,肺泡間隔增寬且出現(xiàn)了水腫,可見較多的中性粒細(xì)胞、巨噬細(xì)胞在肺泡腔內(nèi)聚集。至21天,鏡下觀察模型組可見肺泡腔大部分消失,肺泡間隔斷裂,細(xì)胞結(jié)節(jié)數(shù)量多,炎性細(xì)胞主要是淋巴細(xì)胞和漿細(xì)胞,偶爾可以見到成纖維細(xì)胞。高低劑量組內(nèi),第21天較第7天炎性細(xì)胞大量減少,其中干預(yù)組的炎性細(xì)胞數(shù)量明顯少于模型組,但是與空白對照組比較,仍未恢復(fù)到正常水平。 2.2大鼠肺組織勻漿、血清中炎性因子表達(dá)水平的動態(tài)變化 (1)按照各劑量組比較,相關(guān)因子在模型組中的表達(dá)水平均明顯高于高低劑量組,與高劑量組比較,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。TGF-β1因子表達(dá)水平在模型組中表達(dá)水平略有升高,但無統(tǒng)計(jì)學(xué)差異。 (2)每個(gè)劑量組內(nèi),TNF-α、IL-8、NE、TGF-β1表達(dá)水平在第1天到第7天均見明顯升高,至21天,指標(biāo)水平出現(xiàn)下降,各時(shí)間點(diǎn)之間TNF-α、IL-8、NE具有統(tǒng)計(jì)學(xué)差異性。 [研究結(jié)論] 1大鼠染毒后1-21天內(nèi),肺組織病理學(xué)改變?yōu)樵缙诘难装Y反應(yīng),表現(xiàn)為巨噬細(xì)胞及中心粒細(xì)胞的浸潤聚集,后期的肺泡間隔明顯增厚,成纖維細(xì)胞出現(xiàn),纖維組織開始增生,肺泡正常組織發(fā)生變化,炎性因子在炎癥反應(yīng)過程中發(fā)揮作用。 2染毒大鼠肺組織勻漿和血清中的炎性因子水平隨時(shí)間先升高后降低,并與肺組織病理變化一致,可作為反應(yīng)APQ大鼠肺炎癥及纖維化進(jìn)程的敏感指標(biāo)。 3西維來司鈉干預(yù)大鼠的炎性因子檢測水平明顯低于模型對照組,變化與肺組織病理一致,表明了西維來司鈉在百草枯致ALI的治療中可以對炎性病變起到一定的拮抗作用。 4西維來司鈉干預(yù)組大鼠肺組織的TGF-β1因子未檢測到與對照組存在顯著性差異,提示西維來司鈉對于大鼠肺纖維化的拮抗作用需要進(jìn)一步研究探討。
[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.
【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R595.4
本文編號：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.
【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R595.4
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