阿托伐他汀钙对脂多糖致急性肺损伤大鼠的作用研究

发布时间：2018-07-21 17:37

【摘要】：目的：观察阿托伐他汀钙对脂多糖（LPS）所致急性肺损伤（ALI）大鼠肺组织中血管内皮生长因子（VEGF）、血栓素B2(TXB2）表达和肺泡灌洗液（BALF）中蛋白含量以及中性粒细胞（PMN）比例的影响。探讨阿托伐他汀钙在LPS所致急性肺损伤大鼠中的作用。方法：90只清洁级大鼠随机分为五组，分别为生理盐水(NS)组、LPS组、阿托伐他汀钙小剂量（S）组、阿托伐他汀钙中剂量（M）组、阿托伐他汀钙大剂量（L）组,各组大鼠18只。NS组、LPS组予以NS灌胃，S组、M组和L组分别予以阿托伐他汀钙5mg/Kg/d、10mg/Kg/d、20mg/Kg/d灌胃，各组均连续给药14天，第15天后四组尾静脉注射LPS（6mg/Kg）稀释成1ml制备ALI大鼠模型，NS组尾静脉注射1ml的NS。各组分别于尾静脉注药后2h、4h、8h处死大鼠6只。比较肺组织病理学改变和肺损伤评分；检测各组大鼠肺湿/干重比(W/D)；考马斯亮蓝法测定BALF中蛋白含量同时监测BALF中PMN比例。实时荧光定量逆转录一聚合酶链反应（FQ RT—PCR)检测肺组织VEGF、TXB2mRNA表达；免疫组织化学法测定肺组织中VEGF、TXB2的表达。结果：①病理改变：NS组各时间点大鼠肺组织结构清晰、肺泡壁完整未发现炎性细胞浸润及肺泡间隔水肿。LPS组各时间点肺泡壁破裂，肺泡塌陷实变，肺泡隔及肺泡腔内出血，肺间质水肿、肺泡和间质内有大量中性炎细胞浸润。S组、M组、L组病理改变介于NS组和LPS组之间，以L组损伤最轻，M组其次，S组较重。各组以4h损伤最重，，8h次之，2h最轻。②肺W/D、肺损伤评分:各组大鼠2h、4h、8h均较NS组升高(P0.05), S组、M组和L组在相同时间点较LPS组降低(P0.05)，而M组在同一时间点较S组降低(P0.05)，L组在同一时间点较M组降低(P0.05)。③各组大鼠2h、4h、8hBALF中蛋白含量及PMN比例均较NS组升高(P0.05),S组、M组和L组在相同时间点较LPS组降低(P0.05),而M组在同一时间点较S组降低(P0.05),L组在同一时间点较M组降低(P0.05)。④各组大鼠2h、4h、8h肺组织VEGF、TXB2mRNA表达均较NS组升高(P0.05),S组、M组和L组在相同时间点较LPS组降低(P0.05)，同一时间点，M组较S组降低(P0.05)，L组较M组降低(P0.05)。结论：阿托伐他汀灌胃可降低LPS致ALI大鼠BALF中蛋白含量及PMN比例，其机制可能与肺组织VEGF、TXB2mRNA表达减少微血管通透性降低有关，从而达到保护肺损伤的作用。
[Abstract]:Aim: to observe the effects of Atto vastatin calcium on the expression of vascular endothelial growth factor (VEGF), thromboxane B2 (TXB2), protein content in alveolar lavage fluid (BALF) and the ratio of neutrophil (PMN) in acute lung injury (Ali) induced by lipopolysaccharide (LPS) in rats. To investigate the role of Atto vastatin calcium in LPS-induced acute lung injury in rats. Methods 90 clean rats were randomly divided into five groups: normal saline (NS) group, Atto vastatin calcium small dose (S) group, Atto vastatin calcium medium dose (M) group, Atto vastatin calcium high dose (L) group. 18 rats in the NS group were given intragastric administration of Atto vastatin calcium 5 mg / kg / L group with Atto vastatin calcium 5 mg / kg / d and 20 mg / kg / d respectively. Each group was given the drug continuously for 14 days. After 15 days, the four groups were injected with LPS (6mg / kg) into the tail vein to make Ali rat model. NSs of NS group were injected with 1ml via caudal vein. The rats in each group were killed at 2 h, 4 h and 8 h after intravenous injection. Lung histopathological changes and lung injury scores were compared, lung wet / dry weight ratio (WRD) was measured in each group, and protein content in BALF was determined by Coomassie brilliant blue method, and PMN ratio in BALF was monitored. The expression of VEGF TXB2 mRNA in lung tissue was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (FQ RT-PCR), and the expression of VEGF TXB2 in lung tissue was detected by immunohistochemistry. Results the lung tissue structure was clear at different time points in the control group. No inflammatory cell infiltration and alveolar septal edema were found in the alveolar wall. In LPS group, alveolar wall rupture, alveolar collapse consolidation, alveolar septum hemorrhage and alveolar cavity hemorrhage were found at each time point. Pulmonary interstitial edema, massive infiltration of neutrophils in alveolar and interstitial cells. The pathological changes of group M and group L were between NS group and LPS group. In each group, 4 h injury was the most serious 8 h, followed by 2 h the lightest 2 h lung W / D, lung injury score: the rats in each group were significantly higher than NS group (P0.05), group S and L were lower than LPS group at the same time (P0.05), while M group was lower than S group at the same time (P0.05). At the same time point, the protein content in BALF and the proportion of PMN in BALF of rats in each group were significantly higher than those in NS group (P0.05) at the same time point compared with that in group M (P0.05), while those in group M and group L were lower than those in group LPS at the same time point (P0.05), while those in group M were lower than those in group S at the same time point (P0.05), and the ratio of PMN in group L was lower than that in group S at the same time point (P0.05). The expression of VEGF TXB2 mRNA in lung tissue of rats in the same time group was lower than that in the LPS group at the same time point (P0.05), and the expression of VEGF TXB2 mRNA in the lung tissue of each group was significantly higher than that of the NS group at the same time point (P0.05). At the same time, the expression of VEGF TXB2 mRNA in the lung tissue of the rats in the same time group was lower than that in the LPS group at the same time point (P0.05). Conclusion: Atto vastatin could decrease the protein content and the ratio of PMNs in BALF of rats with Ali induced by LPS. The mechanism may be related to the decrease of microvascular permeability in lung tissue by VEGF- TXB2 mRNA expression, so as to protect lung injury.
【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.8

【相似文献】