本文選題：急性肺損傷 + 脂多糖��； 參考：《中國人民解放軍醫(yī)學(xué)院》2012年碩士論文

【摘要】：目的：急性肺損傷（ALI）的臨床發(fā)病率及致死率均較高，其發(fā)病機(jī)制尚未完全明確。本試驗(yàn)以大腸桿菌脂多糖（LPS）復(fù)制兔ALI模型，通過觀察模型動(dòng)物病理生理變化，進(jìn)一步探討LPS致傷機(jī)制及復(fù)方苦參素的保護(hù)性作用。 方法:21只新西蘭白兔隨機(jī)分為3組:對(duì)照組(A組)、致傷組(B組)和治療組(C組)，每組7只。B, C兩組經(jīng)靜脈一次性注射LPS720μg/kg體重復(fù)制兔的ALI模型，C組同時(shí)經(jīng)靜脈注射復(fù)方苦參注射液4ml/kg體重進(jìn)行干預(yù)治療，A組僅靜脈注射生理鹽水作為對(duì)照，各組分別于0h,0.5h,1h,2h,4h等不同時(shí)間點(diǎn)測定血壓（BP）的變化，并于各點(diǎn)采集動(dòng)脈血進(jìn)行血?dú)夥治�、測定各時(shí)點(diǎn)血液中丙二醛（MDA）和超氧化物歧化酶(SOD)等氧化指標(biāo)、組織纖溶酶原激活劑(t-PA)和纖溶酶原激活物抑制劑（PAI-1）凝血指標(biāo)以及IL-33，IL-35等指標(biāo)，于實(shí)驗(yàn)后4小時(shí)測定肺組織勻漿液中上述指標(biāo)，并行肺組織病理學(xué)觀察。 結(jié)果：A組在實(shí)驗(yàn)過程中各項(xiàng)指標(biāo)均比較平穩(wěn)。A、B、C三組在實(shí)驗(yàn)前各項(xiàng)指標(biāo)沒有統(tǒng)計(jì)學(xué)差異。實(shí)驗(yàn)后各組間有如下變化：1.B組靜脈注射LPS后，血壓、PaO2及OI等指標(biāo)較A組顯著下降，0.5小時(shí)下降最為明顯(P0.01)，C組在給藥后上述三項(xiàng)指標(biāo)同樣下降(P0.01或P0.05)，但介于A組與B組之間;2.實(shí)驗(yàn)進(jìn)程中，B組動(dòng)物血清中IL-33含量較A組顯著升高（P0.01）,呈進(jìn)行性增加。肺組織中IL-33含量較A組亦升高（P0.01）,C組動(dòng)物IL-33含量介于A、B兩組之間;3.B組動(dòng)物靜脈注射LPS后，IL-35的含量逐漸降低，較A組有顯著差異（P0.01）。C組IL-35的含量有降低趨勢，其下降程度較B組有顯著差異（P0.01）。肺組織IL-35的含量低于A組（P0.05），C組較B組略高，但無統(tǒng)計(jì)學(xué)差異，較A組顯著降低（P0.05）;4. B動(dòng)物組靜脈注射LPS后，血清SOD活性呈下降趨勢，與A組比較有統(tǒng)計(jì)學(xué)意義（P0.05）。C組血清SOD活性在實(shí)驗(yàn)過程中有下降趨勢，但介于A組和B組之間，與B組有統(tǒng)計(jì)學(xué)差異（P0.05）。B組動(dòng)物肺組織SOD活性低于A組和C組（P0.01），C組較A組略低無明顯統(tǒng)計(jì)學(xué)意義;5.給LPS后，B組與C組血清MDA值逐步增高(P0.01), C組血清MDA值在1h,2h,4h點(diǎn)低于B組，并且有顯著差異(P0.01)。B組肺組織MDA含量明顯高于A組和C組（P0.01），C組與A組比較無明顯統(tǒng)計(jì)學(xué)意義,C組介于A、B組之間;6. B組靜脈注射LPS后PAI-1含量在各時(shí)間點(diǎn)均有顯著升高（P0.05或P0.01）。C組PAI-1含量略有升高但顯著低于B組（P0.05或P0.01）。B組動(dòng)物肺組織PAI-1含量顯著高于A組(P0.01)和C組（P0.05），C組PAI含量介于A、B組之間;7. B組靜脈注射LPS后，t-PA含量在各時(shí)間點(diǎn)均有顯著升高（P0.01），在2h時(shí)升高幅度較大。C組t-PA含量與A組比較無明顯差異，但較B組有顯著差異（P0.01）。B組動(dòng)物肺組織t-PA含量顯著高于A組和C組（P0.05），，C組與A組比較無明顯統(tǒng)計(jì)學(xué)意義,C組介于A、B組之間；8.實(shí)驗(yàn)4h后，B組肺組織濕/干比顯著高于A組和C組（P0.01），C組明顯高于A組（P0.05）但顯著低于B組（P0.01）；9.病理學(xué)觀察：B組動(dòng)物肺組織易見到ALI典型病理學(xué)表現(xiàn)，C組動(dòng)物較B組損傷明顯減輕，結(jié)構(gòu)與A組相似。 結(jié)論：一次性靜脈注射脂多糖(720ug/kg)可以復(fù)制兔ALI動(dòng)物模型。炎癥反應(yīng)失控，促炎反應(yīng)和杭炎反應(yīng)平衡失調(diào)；氧化損傷和抗氧化相對(duì)不足；凝血纖溶異常均參與LPS致急性肺損傷的發(fā)病。致傷組肺組織血管出現(xiàn)內(nèi)皮細(xì)胞腫脹、突起，炎性細(xì)胞浸潤、扣押，血管擴(kuò)張、微血栓形成微循環(huán)障礙等一系列病理生理變化。復(fù)方苦參注射液通過維持凝血纖溶系統(tǒng)相對(duì)平衡，提高抗氧化能力及拮抗炎性介質(zhì)等多種機(jī)理對(duì)受損肺組織起一定的保護(hù)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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R285.5;R563.8

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相關(guān)期刊論文 前6條

1 侯偉;劉海燕;楊旭東;李靜;周戩平;李丹;楊智毅;葛利吉;;氧化苦參堿對(duì)哮喘小鼠肺組織中TGF-β1及AngII表達(dá)的影響[J];中國兒童保健雜志;2010年02期

2 葉友q

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