脂多糖致兔急性肺损伤及复方苦参注射液保护作用的研究

发布时间：2018-05-17 03:05

本文选题：急性肺损伤 + 脂多糖　；参考：《中国人民解放军医学院》2012年硕士论文

【摘要】：目的：急性肺损伤（ALI）的临床发病率及致死率均较高，其发病机制尚未完全明确。本试验以大肠杆菌脂多糖（LPS）复制兔ALI模型，通过观察模型动物病理生理变化，进一步探讨LPS致伤机制及复方苦参素的保护性作用。方法:21只新西兰白兔随机分为3组:对照组(A组)、致伤组(B组)和治疗组(C组)，每组7只。B, C两组经静脉一次性注射LPS720μg/kg体重复制兔的ALI模型，C组同时经静脉注射复方苦参注射液4ml/kg体重进行干预治疗，A组仅静脉注射生理盐水作为对照，各组分别于0h,0.5h,1h,2h,4h等不同时间点测定血压（BP）的变化，并于各点采集动脉血进行血气分析、测定各时点血液中丙二醛（MDA）和超氧化物歧化酶(SOD)等氧化指标、组织纤溶酶原激活剂(t-PA)和纤溶酶原激活物抑制剂（PAI-1）凝血指标以及IL-33，IL-35等指标，于实验后4小时测定肺组织匀浆液中上述指标，并行肺组织病理学观察。结果：A组在实验过程中各项指标均比较平稳。A、B、C三组在实验前各项指标没有统计学差异。实验后各组间有如下变化：1.B组静脉注射LPS后，血压、PaO2及OI等指标较A组显著下降，0.5小时下降最为明显(P0.01)，C组在给药后上述三项指标同样下降(P0.01或P0.05)，但介于A组与B组之间;2.实验进程中，B组动物血清中IL-33含量较A组显著升高（P0.01）,呈进行性增加。肺组织中IL-33含量较A组亦升高（P0.01）,C组动物IL-33含量介于A、B两组之间;3.B组动物静脉注射LPS后，IL-35的含量逐渐降低，较A组有显著差异（P0.01）。C组IL-35的含量有降低趋势，其下降程度较B组有显著差异（P0.01）。肺组织IL-35的含量低于A组（P0.05），C组较B组略高，但无统计学差异，较A组显著降低（P0.05）;4. B动物组静脉注射LPS后，血清SOD活性呈下降趋势，与A组比较有统计学意义（P0.05）。C组血清SOD活性在实验过程中有下降趋势，但介于A组和B组之间，与B组有统计学差异（P0.05）。B组动物肺组织SOD活性低于A组和C组（P0.01），C组较A组略低无明显统计学意义;5.给LPS后，B组与C组血清MDA值逐步增高(P0.01), C组血清MDA值在1h,2h,4h点低于B组，并且有显著差异(P0.01)。B组肺组织MDA含量明显高于A组和C组（P0.01），C组与A组比较无明显统计学意义,C组介于A、B组之间;6. B组静脉注射LPS后PAI-1含量在各时间点均有显著升高（P0.05或P0.01）。C组PAI-1含量略有升高但显著低于B组（P0.05或P0.01）。B组动物肺组织PAI-1含量显著高于A组(P0.01)和C组（P0.05），C组PAI含量介于A、B组之间;7. B组静脉注射LPS后，t-PA含量在各时间点均有显著升高（P0.01），在2h时升高幅度较大。C组t-PA含量与A组比较无明显差异，但较B组有显著差异（P0.01）。B组动物肺组织t-PA含量显著高于A组和C组（P0.05），，C组与A组比较无明显统计学意义,C组介于A、B组之间；8.实验4h后，B组肺组织湿/干比显著高于A组和C组（P0.01），C组明显高于A组（P0.05）但显著低于B组（P0.01）；9.病理学观察：B组动物肺组织易见到ALI典型病理学表现，C组动物较B组损伤明显减轻，结构与A组相似。结论：一次性静脉注射脂多糖(720ug/kg)可以复制兔ALI动物模型。炎症反应失控，促炎反应和杭炎反应平衡失调；氧化损伤和抗氧化相对不足；凝血纤溶异常均参与LPS致急性肺损伤的发病。致伤组肺组织血管出现内皮细胞肿胀、突起，炎性细胞浸润、扣押，血管扩张、微血栓形成微循环障碍等一系列病理生理变化。复方苦参注射液通过维持凝血纤溶系统相对平衡，提高抗氧化能力及拮抗炎性介质等多种机理对受损肺组织起一定的保护作用。
[Abstract]:Objective: the incidence and fatality rate of acute lung injury (ALI) were both high and its pathogenesis was not completely clear. The rabbit model of ALI was replicated by LPS in this experiment. The mechanism of LPS injury and the protective effect of compound matrine were further investigated by observing the pathophysiological changes of the model animals.
Methods: 21 New Zealand white rabbits were randomly divided into 3 groups: the control group (group A), the injury group (group B) and the treatment group (group C), 7.B in each group. The ALI model of the rabbits was replicated by intravenous injection of LPS720 mu g/kg weight by intravenous injection of C, and the C group was treated by intravenous injection of compound Sophora flavescens on 4ml/kg weight at the same time, and the A group was only injected with normal saline as the control. The changes of blood pressure (BP) were measured at different time points, such as 0h, 0.5h, 1H, 2h, 4h, and the blood gas analysis was collected at each point. The oxidation indexes such as malondialdehyde (MDA) and superoxide dismutase (SOD) in the blood of each point were measured, and the coagulation indexes of fibrinolytic plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were measured and IL-. 33, IL-35 and other indicators were used to determine the above indexes in lung homogenate at 4 hours after experiment, and pathological observation was carried out in lung tissue.
Results: the indexes of group A in the experimental process were all stable.A, B, C three groups before the experiment, there were no statistical differences. After the experiment, there were the following changes in each group: after the 1.B group, the blood pressure, PaO2 and OI were significantly lower than those in the A group after the intravenous injection of LPS, and the most obvious (P0.01) decreased in the 0.5 hours (P0.01), and the three indexes of the C group were the same after the administration. Decreased (P0.01 or P0.05), but between group A and group B; in the 2. experimental process, the content of IL-33 in the serum of B group was significantly higher than that in the A group (P0.01), showing an progressive increase. The content of IL-33 in the lung tissue was also higher than that in the A group (P0.01). The content of IL-35 in group.C was significantly lower than that of group B (P0.01). The content of IL-35 in lung tissue was lower than that of group A (P0.05), and the group C was slightly higher than that of B group, but there was no statistical difference between the A group and the A group (P0.05). After the intravenous injection of the 4. animal group, the activity of serum was decreased, and there was a statistical difference compared with that of the 4. group. Serum SOD activity in P0.05.C group decreased in the experimental process, but between group A and B group, and there was a statistical difference between group A and group B (P0.05) the SOD activity of lung tissue in.B group was lower than that of A group and C group (P0.01). The 2H and 4H points were lower than that of the B group, and there were significant differences in the MDA content in the lung tissue of the.B group (P0.01), and there was no significant difference between the A group and the C group (P0.01). The C and A groups had no significant statistical significance. The C group was between the 6. groups. The content of PAI-1 in P0.05 or P0.01 group.B was significantly higher than that in group A (P0.01) and C group (P0.05). The PAI content of C group was between A and B groups. T-PA content in animal lung tissue was significantly higher than that in group A and group C (P0.05), and there was no significant statistical significance between group C and group A, C group was between A and B groups. After 8. experimental 4h, the wet / dry ratio of lung tissue in B group was significantly higher than that in A group and group. Typical pathological findings showed that the damage of group C was significantly less than that of group B, and the structure was similar to that of group A.
Conclusion: one time intravenous injection of lipopolysaccharide (720ug/kg) can replicate the rabbit model of ALI animal. The inflammatory reaction is out of control, the proinflammatory reaction and the imbalance of the inflammatory reaction, the oxidative damage and the relative deficiency of antioxidant, and the abnormal coagulation and fibrinolysis are all involved in the pathogenesis of acute lung injury caused by LPS. The endothelial cells in the lung tissue of the injured group are swelling, protruding and inflamed. A series of pathophysiological changes, such as sexual cell infiltration, seizure, vasodilatation, microcirculation obstruction, and so on. Compound Sophora flavescens injection can protect the damaged lung by maintaining the relative balance of coagulation and fibrinolysis system, improving the anti-oxidation ability and antagonizing the inflammatory mediators.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285.5;R563.8

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