本文選題：減壓病 + 快速上浮脫險(xiǎn)��； 參考：《第二軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：目的:在以快速上浮脫險(xiǎn)方法進(jìn)行逃生的過程中,失事潛艇艇員可因高壓暴露時(shí)間超過允許的安全時(shí)間而使體內(nèi)溶解的惰性氣體原地生成氣泡,進(jìn)而導(dǎo)致減壓病(decompression sickness,DCS)的發(fā)生。本研究目的是觀察肌苷預(yù)處理對(duì)模擬不安全快速上浮脫險(xiǎn)大鼠DCS發(fā)病的預(yù)防作用并探索相關(guān)機(jī)制。方法:1.以成年雄性Wistar大鼠為研究對(duì)象,隨機(jī)分為正常對(duì)照組、DCS對(duì)照組、低劑量肌苷組、中劑量肌苷組、高劑量肌苷組、氯吡格雷組。除正常對(duì)照組外,大鼠經(jīng)“以PT=P0′2T/7指數(shù)曲線加壓至1.6 MPa并穩(wěn)壓242 s后,以3 m/s速率勻速減至0.1 MPa”的加壓-減壓方案處理。低/中/高劑量肌苷組分別在加壓前30 min腹腔給肌苷50/100/200 mg/kg,氯吡格雷組在加壓前連續(xù)3 d管飼氯吡格雷50mg/kg/日。正常對(duì)照組、DCS對(duì)照組加壓前30 min給同體積的生理鹽水。出艙后觀察各組發(fā)病和死亡情況,并在0.5 h、12 h、24 h檢測(cè)肺組織的病理、濕干重比、炎癥因子(TNF-a、IL-6)、凋亡因子(Bcl-2、Bax、caspase-3)、MAPK通路蛋白(ERK、p38、JNK)的變化情況。2.根據(jù)前期實(shí)驗(yàn)結(jié)果選擇100 mg/kg肌苷、0.5 h取材檢測(cè)的方案,在使用肌苷預(yù)處理的基礎(chǔ)上分別利用A_(2A)受體拮抗劑SCH52861、A_3受體拮抗劑MRS1523、ERK通路阻斷劑AZD6244處理大鼠,觀察特異性拮抗劑對(duì)肌苷改善DCS發(fā)病、肺病理損傷、炎癥反應(yīng)、凋亡反應(yīng)等的影響,探究A_(2A)受體、A_3受體、ERK通路在肌苷預(yù)防DCS機(jī)制中的作用。結(jié)果:1.模擬不安全快速上浮脫險(xiǎn)可造成大鼠DCS的發(fā)生(發(fā)病率95%,死亡率50%)。與正常對(duì)照組比,DCS對(duì)照組可見肺組織的病理評(píng)分、濕干重比、TNF-a、IL-6增加,凋亡因子caspase-3激活上調(diào),抗凋亡指標(biāo)Bcl-2/Bax下降。2.和DCS對(duì)照組比,100~200 mg/kg肌苷可有效改善大鼠DCS的發(fā)病和死亡情況,且效果與氯吡格雷基本相當(dāng)。肌苷還可降低肺病理評(píng)分、濕干重比、TNF-a、IL-6和裂解型caspase-3水平,上調(diào)Bcl-2/Bax和ERK激活水平。與12 h、24 h相比,此現(xiàn)象在出艙后0.5 h最明顯。3.在肌苷預(yù)處理之前使用A_(2A)受體拮抗劑SCH52861、A_3受體拮抗劑MRS1523、ERK通路阻斷劑AZD6244,可使大鼠DCS相關(guān)損傷指標(biāo)加重,減弱了肌苷的這種預(yù)防作用。結(jié)論:1.不安全的快速上浮脫險(xiǎn)可導(dǎo)致DCS的發(fā)生,在12 h內(nèi),大鼠可表現(xiàn)出明顯的肺組織病理損傷和水腫、炎癥反應(yīng)和凋亡水平升高。2.100 mg/kg肌苷預(yù)處理可有效改善DCS發(fā)病、死亡情況和肺組織損傷、炎癥反應(yīng)、凋亡情況,且在DCS早期即可發(fā)揮明顯的保護(hù)作用。3.肌苷可通過結(jié)合A_(2A)受體、A_3受體使ERK信號(hào)通路激活,進(jìn)而上調(diào)抗凋亡因子,降低凋亡水平,產(chǎn)生保護(hù)肺組織、改善DCS發(fā)病死亡情況的作用。
[Abstract]:Objective: in the process of escape by fast floating escape, shipwrecked submarine crew can cause the dissolved inert gas to form bubbles in situ because the time of high pressure exposure exceeds the permitted safe time, and then lead to decompression decompression syndrome (DCSs).The aim of this study was to investigate the preventive effect of inosine pretreatment on the pathogenesis of DCS in simulated unsafe and fast floating rats.Method 1: 1.Adult male Wistar rats were randomly divided into normal control group, low dose inosine group, middle dose inosine group, high dose inosine group and clopidogrel group.In addition to the normal control group, the rats were treated with a pressure-decompression regimen of "pressurized with PT=P0'2T/7 exponent curve to 1.6 MPa and steady pressure for 242s, and reduced to 0.1 MPa at a rate of 3 m / s".The low / middle / high dose inosine group was intraperitoneally given inosine 50 / 100 / 200 mg / kg 30 min before compression, while clopidogrel group was given clopidogrel 50mg/kg/ day for 3 days before compression.The normal control group was given the same volume of normal saline 30 min before compression.The incidence and death of each group were observed, and the pathological changes of lung tissue, wet dry weight ratio (WDW), TNF-a IL-6 and apoptosis factor Bcl-2BaxCaspase-3 MAPK pathway protein ERK p38 JNK2 were detected at 0.5 h and 12 h and 24 h respectively.According to the results of the previous experiment, we selected the method of #number0# mg/kg inosine for 0. 5 h. On the basis of pretreatment with inosine, we treated the rats with AZD6244, a receptor antagonist, SCH 52861A 3 receptor antagonist, MRS1523 ERK pathway blocker, respectively, on the basis of pretreatment with inosine.To observe the effects of specific antagonists on the effects of inosine on the pathogenesis of DCS, lung pathological injury, inflammatory reaction and apoptosis reaction, and to explore the role of the A3 receptor ERK pathway in the prevention of DCS by inosine.The result is 1: 1.Simulated unsafe fast buoyancy can lead to the occurrence of DCS in rats (incidence 95%, mortality 50%).Compared with normal control group, lung tissue pathological score, wet and dry weight increased, apoptosis factor caspase-3 activation increased, and Bcl-2/Bax decreased by 0.2, compared with normal control group.Compared with the control group of DCS, the inosine of 200 mg/kg could effectively improve the incidence and death of DCS in rats, and the effect was almost the same as that of clopidogrel.Inosine also decreased lung pathological score, wet / dry weight ratio (WDW), TNF-a IL-6 and lytic caspase-3, and upregulated the activation of Bcl-2/Bax and ERK.Compared with 12 h / 24 h, this phenomenon was the most obvious at 0.5 h after departure.Before the pretreatment of inosine, the antagonist SCH 52861A / S 3 receptor antagonist MRS 1523 ERK pathway blocker AZD6244 could aggravate the damage index of DCS in rats and weaken the preventive effect of inosine.Conclusion 1.Unsafe rapid floating escape can lead to the occurrence of DCS. Within 12 h, the rats showed obvious lung tissue pathological injury and edema. Pretreatment with increased level of inflammatory reaction and apoptosis. 2.100 mg/kg inosine pretreatment could effectively improve the pathogenesis of DCS.Death and lung tissue injury, inflammation, apoptosis, and early DCS can play a significant protective role. 3.Inosine can activate the ERK signaling pathway by binding with Astack 2A) receptor, and then up-regulate the anti-apoptotic factor, decrease the level of apoptosis, protect lung tissue and improve the incidence and death of DCS.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R845.21

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 攸璞;方以群;王海濤;包曉辰;張師;馬駿;王芳芳;;快速上浮脫險(xiǎn)致減壓病動(dòng)物肺組織病理改變的研究[J];軍事醫(yī)學(xué);2014年07期

2 包曉辰;方以群;王芳芳;攸璞;馬駿;;氯吡格雷對(duì)減壓病的預(yù)防作用[J];軍事醫(yī)學(xué);2014年07期

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本文編號(hào)：1756223