本文選題：煙霧吸入損傷 + TNF-α��； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：背景和目的燒傷伴有吸入性肺損傷能引起多種器官障礙進(jìn)而出現(xiàn)較高的發(fā)病率及死亡率。成立照料燒傷患者所需成本對(duì)醫(yī)療制度是一種巨大的負(fù)擔(dān)。在過(guò)去十年中,減低燒傷死亡率已經(jīng)取得重要進(jìn)展,但治療仍遠(yuǎn)非理想。煙霧吸入性損傷所導(dǎo)致的急性肺損傷(ALI)是以肺水腫、肺組織缺氧及中性粒細(xì)胞浸潤(rùn)為特征,其主要發(fā)病率及致死率多與休克、敗血癥、缺血再灌注等有關(guān),是常見(jiàn)的臨床問(wèn)題。這些急性炎癥反應(yīng)也可以概括為炎癥細(xì)胞聚集,蛋白質(zhì)泄漏至肺泡中,致間質(zhì)水腫,破壞上皮的完整性。而NF-kB需要許多細(xì)胞因子轉(zhuǎn)錄,包括TNF-α、IL-1β。在急性肺損傷早期階段,這些細(xì)胞因子被細(xì)菌內(nèi)毒素通過(guò)NF-KB信號(hào)并釋放。并且,凋亡通路所出現(xiàn)的異常調(diào)控在急性肺損傷中肺組織失去正常功能細(xì)胞中具有重要作用。辛伐他汀為羥甲基戊二酰輔酶A(HMG-COA)還原酶抑制劑,近年來(lái)大量實(shí)驗(yàn)發(fā)現(xiàn),辛伐他汀不但有降脂作用,在急性肺損傷中還表現(xiàn)出多效性,包含促進(jìn)炎癥細(xì)胞凋亡、抗炎、改善血管內(nèi)皮功能等。有文獻(xiàn)報(bào)道他汀類中辛伐他汀可阻斷許多炎性因子和細(xì)胞因子的釋放和功能表達(dá),如TNF-a、IL-6、NF-kB等,通過(guò)降低這些炎癥反應(yīng)介質(zhì)在血清中的表達(dá),進(jìn)而抑制局部和全身的炎癥反應(yīng)。因此本實(shí)驗(yàn)通過(guò)研究辛伐他汀對(duì)煙霧所致吸入性肺損傷大鼠炎癥及抗炎介質(zhì)的影響,觀察其對(duì)煙霧所致吸入性肺損傷的抑制作用。實(shí)驗(yàn)一煙霧吸入性肺損傷大鼠模型的制備方法將48只清潔級(jí)大鼠按隨機(jī)化原則分為四組,分別為對(duì)照組、6min組、7min組、8min組,每組12只。采納自制煙霧致傷設(shè)備分別給予6min組、7min組、8min組大鼠行對(duì)應(yīng)時(shí)間的煙霧吸入性損傷,煙霧致傷后分別于6h、12h、24h這三個(gè)時(shí)相進(jìn)行觀察各組大鼠臨床表現(xiàn)、存活率及煙霧致傷后24h存活大鼠的肺組織病理情況。結(jié)果1.臨床表現(xiàn):正常組大鼠靜息狀態(tài)下無(wú)明顯異常,致傷后的所有大鼠均出現(xiàn)呼吸急促,頻率達(dá)120-140次/分,口唇紫紺,鼻腔及口唇可見(jiàn)黑色煙灰沉著,被毛濕潤(rùn),結(jié)膜充血,6min組傷后活動(dòng)飲食逐漸正常;7min組大鼠活動(dòng)減少,精神萎靡不振,攝食減少,伴有喘鳴,部分大鼠逐漸恢復(fù)正常;8min組大鼠于致傷后活動(dòng)明顯減少,精神明顯萎靡不振,攝食明顯減少,伴有喘鳴。2.存活率:煙霧致傷后四組大鼠存活率對(duì)照,7min組與6min組、正常組對(duì)照三個(gè)時(shí)相的大鼠存活率無(wú)明顯差異(P0.05);8min組較6min組、正常組三個(gè)時(shí)相的大鼠存活率低(P0.05),于24h較7min組的大鼠存活率低(P0.05)。3.煙霧致傷24h后各組存活大鼠的肺組織病理學(xué)評(píng)分對(duì)比,三組與正常組大鼠肺組織病理學(xué)評(píng)分均有統(tǒng)計(jì)學(xué)意義P0.05㖞,7min組大鼠肺組織病理學(xué)評(píng)分高于6min組P0.05㖞,8min組大鼠肺組織病理學(xué)評(píng)分高于7min組P0.05㖞。結(jié)論參考其他煙霧所致吸入性損傷模型的制備基礎(chǔ)上,本實(shí)驗(yàn)采用以木屑為燃燒原料,自制致傷室模擬火災(zāi)現(xiàn)場(chǎng),以大鼠為對(duì)象制作煙霧所致吸入性損傷模型,致傷7min組大鼠能至中重度煙霧吸入性肺損傷,存活率較高,且該模型操作簡(jiǎn)單,重復(fù)性高,成本低廉,能滿足本課題研究需要。實(shí)驗(yàn)二辛伐他汀抑制煙霧吸入引起的大鼠急性肺損傷及其機(jī)制研究方法健康成年SD大鼠54只,隨機(jī)化原則分為正常組、鹽水組、辛伐他汀組,辛伐他汀組大鼠煙霧致傷后,用灌胃器灌入實(shí)驗(yàn)藥物—辛伐他汀50mg/kg,每日一次,鹽水組大鼠煙霧致傷后灌入與辛伐他汀組相同量的生理鹽水,正常組作為基礎(chǔ)值,不做任何處理。三組大鼠分別于灌液后6h、24h、48h這三個(gè)時(shí)相采取大鼠動(dòng)脈血離心后血清、左肺肺泡灌洗液上清應(yīng)用ELISA法測(cè)定TNF-a、IL-6的含量,并取右肺上葉組織提取蛋白后應(yīng)用Western Blot法測(cè)定TNF-a、IL-6、NF-kB的蛋白表達(dá)情況。于灌液48h后取右肺下葉行HE病理染色。各組各時(shí)相大鼠6只。結(jié)果1.煙霧吸入性肺損傷后,鹽水組、辛伐他汀組血清及肺泡灌洗液中TNF-α、IL-6的含量均明顯升高,在不同觀察時(shí)相均明顯高于正常組(P0.05),辛伐他汀治療組血清及肺泡灌洗液中TNF-α、IL-6含量與鹽水組相比,除6h時(shí)相外,其它三個(gè)時(shí)相均有顯著降低(P0.05)。2.鹽水組、辛伐他汀組TNF-α、IL-6及NF-kB蛋白表達(dá)較正常組明顯升高,有統(tǒng)計(jì)學(xué)差異(P0.05);而辛伐他汀組與鹽水組相比,除6h時(shí)相外,TNF-α、IL-6及NF-kB蛋白的表達(dá)均明顯減少,有統(tǒng)計(jì)學(xué)差異(P0.05)。3.灌液48h后顯微鏡下正常組大鼠肺泡腔清晰、完整、潔凈,肺泡間隔勻稱無(wú)腫脹,間質(zhì)無(wú)炎性細(xì)胞聚集;鹽水組大鼠肺組織有明顯充血、出血,肺泡結(jié)構(gòu)破壞,肺泡間隔增厚,間質(zhì)有大量的炎癥細(xì)胞浸潤(rùn)等;辛伐他汀組病理改變均較鹽水組明顯減輕。結(jié)論辛伐他汀能降低煙霧吸入性損傷大鼠肺組織及血清中TNF-a、IL-6和NF-kB的水平,對(duì)大鼠早期煙霧肺損傷有保護(hù)作用。
[Abstract]:Background and objective burns accompanied by inhaled lung injury can cause a variety of organ disorders and higher morbidity and mortality. The cost of caring for burn patients is a huge burden on the medical system. In the past ten years, the reduction of burn mortality has been an important development, but the treatment is still far from ideal. Smoke inhalation loss Acute lung injury (ALI) caused by injury is characterized by pulmonary edema, hypoxia and neutrophil infiltration in the lung. The main morbidity and mortality are associated with shock, septicemia, and ischemia reperfusion, which are common clinical problems. These acute inflammatory reactions can also be included in the accumulation of inflammatory cells, protein leaks into the alveoli, and caused to the alveoli. NF-kB requires a lot of cytokine transcription, including TNF- alpha, IL-1 beta. In the early stage of acute lung injury, these cytokines are transmitted by the bacterial endotoxin through the NF-KB signal. And the abnormal regulation of the apoptotic pathway in the lung tissue loses the normal function of the lung tissue in acute lung injury. Action. Simvastatin is a hydroxymethyl amyl two acyl coenzyme A (HMG-COA) reductase inhibitor. In recent years, a large number of experiments have found that simvastatin not only has the effect of lowering lipid, but also shows a pleiotropic effect in acute lung injury, including promoting inflammatory cell apoptosis, anti-inflammatory, and improving vascular endothelial function. The release and functional expression of many inflammatory factors and cytokines, such as TNF-a, IL-6, NF-kB, and so on, inhibit the expression of these inflammatory mediators in the serum and then inhibit the local and systemic inflammatory response. The preparation method of the model of smoke inhalation lung injury was divided into four groups according to the randomization principle of 48 rats. The control group, 6min group, 7min group, group 8min, group 8min, each group of 12 rats were given the 6min group, 7min group and 8min group, respectively. The smoke inhalation injury at the time of smoke inhalation and the three phases of 6h, 12h and 24h were observed respectively after the smoke injury. The survival rate and the lung histopathology of the 24h surviving rats after the smog injury were observed. Results the 1. clinical manifestations were as follows: the normal group rats had no obvious abnormality in the resting state, and all the rats after the injury occurred respiratory shortness. The frequency of 120-140 times / minutes, cyanosis of lips, nasal and lip black soot, wet hair, conjunctiva hyperemia, 6min group after injury, active diet gradually normal, 7min group rats activity decreased, mental malaise, less food, accompanied by wheezing, some rats gradually recovered normal; group 8min rats after injury significantly decreased activity, mental brightness after injury obviously, spirit Ming rats after injury obviously decreased, mental brightness after injury, mental Ming rats after injury obviously decreased, mental brightness after injury, mental Ming rats after injury obviously reduced activities after injury, mental Ming after injury, mental Ming rats after injury obviously decreased, mental brightness after injury, mental Ming after injury, mental Ming obviously decreased after injury, mental Ming rats after injury obviously decreased after injury, mental Ming rats after injury obviously decreased, mental brightness after injury, mental Ming rats after injury obviously reduced activities after injury, mental Ming after injury, mental bright rats after injury obviously decreased, mental Ming after injury, mental Ming after injury, mental Ming obviously decreased after injury, mental Ming rats after injury significantly decreased, mental after injury, mental Ming rats after injury obviously decreased, mental brightness after injury, mental Ming after injury, mental bright rats after injury obviously decreased, mental Ming after injury, mental Ming after injury significantly reduced The survival rate of the four rats in the four groups after the smoke injury was compared, the survival rate of the rats in the 7min group and the 6min group and the control group of the normal group were not significantly different (P0.05). The survival rate of the rats in the group 8min was lower than that of the normal group (P0.05), and the survival rate of the 24h compared to the 7min group was low (P0.0, P0.0, P0.0, P0.0, P0.0, and P0.0), and the survival rate was lower in the 24h than the 7min group (P0.0). 5) compared with the lung histopathology score of the survival rats in each group after.3. smoke injury 24h, the pathological score of lung tissue in the three group and the normal group was statistically significant? P0.05? The lung histopathological score of group 7min rats was higher than that of the 6min group? P0.05? The lung histopathological score of group 8min rats was higher than that of the 7min group? P0.05? Conclusions reference to the other smog. On the basis of the preparation of inhalation damage model, this experiment uses wood chips as combustion materials, self-made injury chamber to simulate fire scene. The model of inhalation injury caused by smoke is made in rats, and the rats in group 7min can be injured to moderate to severe smoke inhalation lung injury, the survival rate is high, and the model is simple to operate, high repeatability and low cost. Experimental two simvastatin inhibits the acute lung injury of rats induced by smoke inhalation and its mechanism research methods: 54 healthy adult SD rats. The principle of randomization is divided into normal group, saline group, simvastatin group, simvastatin group and simvastatin 50mg/kg after smog injury in simvastatin group. Once a day, the rats in the saline group were injected with the same amount of normal saline with the simvastatin group after the smoke injury. The normal group was used as the base value and did not do any treatment. The three groups of rats were divided into the three phases of 6h, 24h, and 48h after the irrigation. The left lung alveolar lavage supernatant was used to determine the content of TNF-a, IL-6, and the left lung alveolar lavage fluid supernatant. The protein expression of TNF-a, IL-6, NF-kB was measured by Western Blot method after extracting the right upper lobe tissue. After 48h, HE pathological staining was performed in the right lower lobe of the lung. 6 rats in each group were observed. The results showed that the levels of TNF- A and IL-6 in the serum and alveolar lavage fluid in the 1. smoke inhalation group, in the simvastatin group, in the simvastatin group and in the serum and alveolar lavage fluid were significantly increased. Compared with the normal group (P0.05), the content of TNF- alpha and IL-6 in the serum and alveolar lavage fluid of simvastatin group was significantly lower than that of the saline group. The other three phases were significantly decreased (P0.05).2. saline group, and the expression of TNF- alpha, IL-6 and NF-kB protein in simvastatin group was significantly higher than that in the normal group (P, P). There was a statistically significant difference (P). 0.05) 0.05) but compared with the saline group, the expression of TNF- alpha, IL-6 and NF-kB in the simvastatin group was significantly reduced, and there was a statistically significant difference (P0.05).3. perfusion 48h after 48h, the alveolar cavity in the normal group was clear, complete, clean, and the alveolar septum was unswollen and interstitial without inflammatory cell aggregation; the lung tissue of the saline group was obviously filled. Blood, bleeding, alveolar structure damage, alveolar septum thickening, mass of inflammatory cell infiltration, and the pathological changes of simvastatin group were significantly lower than that of saline group. Conclusion simvastatin can reduce the level of TNF-a, IL-6 and NF-kB in lung tissue and serum of smoke inhalation injury rats, and have protective effect on early smoke and lung injury in rats.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R563.8

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