【摘要】：目的探討急性呼吸窘迫綜合征(ARDS)行控制性肺膨脹(SI)的治療效果,并觀察SI在分子生物學(xué)水平上對ARDS的影響,初步探索其可能的分子生物學(xué)機(jī)制,以期為臨床治療ARDS提供參考依據(jù)。 方法20只成年雄性Beagle犬,麻醉后接呼吸機(jī)予以基礎(chǔ)通氣,利用油酸建立犬ARDS模型。穩(wěn)定30min后隨機(jī)分成2組。非SI組：予以一次密閉式吸痰,吸痰后不給予ARDS犬控制性肺膨脹。SI組：予以一次密閉式吸痰后立即給予ARDS犬一次控制性肺膨脹,SI采用持續(xù)氣道正壓通氣(CPAP)模式,CPAP設(shè)置為30cmH2O持續(xù)30秒,結(jié)束后恢復(fù)基礎(chǔ)通氣。監(jiān)測吸痰前、吸痰后3min、15min、30min、60min、120min、240min的動脈血?dú)�、血流動力學(xué)指標(biāo)、呼吸力學(xué)指標(biāo)等。油酸前、成模后、吸痰后1小時、吸痰后4小時分別用酶聯(lián)免疫吸附法(ELISA)檢測各組ARDS犬血清中TNF-α、IL-1β、IL-6、IL-10、SP-A和HMGB1。吸痰后4小時靜脈注射氯化鉀處死ARDS犬,取肺臟標(biāo)本RT-PCR檢測肺組織中AQP-1、AQP-5、SP-A、HMGB1、FLIP和IL-6mRNA的表達(dá),并觀察其普通病理。 結(jié)果SI提高了ARDS犬密閉式吸痰后的動脈氧分壓和靜態(tài)肺順應(yīng)性(P0.05),降低了氣道阻力(P0.05),并且SI對ARDS犬的血流動力學(xué)指標(biāo)未產(chǎn)生明顯的影響。在分子生物學(xué)水平,SI降低了ARDS犬血清中促炎細(xì)胞因子(TNF-α、IL-1β、IL-6)和抗炎細(xì)胞因子(IL-10)的濃度(P0.05),降低了血清SP-A的水平(P0.05)。在肺組織中,SI能增加AQP-1、AQP-5和FLIP mRNA的表達(dá)(P0.05),減少IL-6mRNA的表達(dá)(P0.05)。而遲發(fā)型炎癥因子(HMGB1)在血清和肺組織中的水平兩組比較均無明顯統(tǒng)計(jì)學(xué)差異。 結(jié)論實(shí)施SI能安全、有效的改善ARDS的氧合、提高肺順應(yīng)性,改善密閉式吸痰后的低氧血癥狀態(tài)。其可能的分子生物學(xué)機(jī)制為：SI減輕了剪切力對肺泡上皮細(xì)胞及血管內(nèi)皮細(xì)胞的機(jī)械刺激,抑制了肺組織中炎癥介質(zhì)的mRNA表達(dá),也減少了全身炎癥介質(zhì)的釋放。炎癥介質(zhì)分泌的減少,減輕了肺局部炎癥反應(yīng)和肺泡毛細(xì)血管屏障的損傷,肺內(nèi)SP-A丟失減少,肺泡張力降低,從而預(yù)防肺泡塌陷。肺泡毛細(xì)血管屏障受損減輕,肺組織內(nèi)AQP-1和AQP-5表達(dá)增加,加強(qiáng)了機(jī)體清除水腫液的能力,減輕了肺泡和間質(zhì)的水腫,改善了氧合。炎癥細(xì)胞因子產(chǎn)生減少,肺組織中FLIP表達(dá)增高,抑制了肺血管內(nèi)皮細(xì)胞、肺泡上皮細(xì)胞的凋亡。因此SI減少炎癥介質(zhì)分泌、上調(diào)水通道蛋白、減少肺內(nèi)SP-A丟失等引起的上述一系列變化可能最終達(dá)到改善肺順應(yīng)性和氧合的目的。
[Abstract]:Objective to investigate the therapeutic effect of (ARDS) on (SI), observe the effect of SI on ARDS at molecular level, and explore its possible molecular biological mechanism. In order to provide reference for clinical treatment of ARDS. Methods Twenty adult male Beagle dogs were treated with ventilator after anesthesia and ARDS model was established by oleic acid. After stable 30min, they were randomly divided into two groups. In non-SI group, once closed aspiration was given, and ARDS dog was not given control pulmonary expansion after sucking sputum. SI group: ARDS dog was given once controlled pulmonary expansion immediately after once closed suction. SI was treated with (CPAP) mode of continuous positive airway pressure ventilation. CPAP was set to 30cmH2O for 30 seconds, after which basic ventilation was restored. The arterial blood gas, hemodynamics, respiratory mechanics and so on were monitored before and 3 min after sputum aspiration. TNF- 偽, IL-1 尾, IL-6,IL-10,SP-A and HMGB1. in serum of ARDS dogs in each group were detected by enzyme linked immunosorbent assay (ELISA) before, after modeling, 1 hour after sputum aspiration and 4 hours after sputum aspiration. ARDS dogs were killed by intravenous injection of potassium chloride 4 hours after sputum aspiration. The expression of AQP-1,AQP-5,SP-A,HMGB1,FLIP and IL-6mRNA in lung tissue was detected by RT-PCR and the pathological changes were observed. Results SI increased arterial oxygen pressure and static pulmonary compliance after closed sputum aspiration in ARDS dogs (P0.05), decreased airway resistance (P0.05), and SI had no significant effect on hemodynamics of ARDS dogs. At the level of molecular biology, SI decreased the concentration of TNF- 偽, IL-1 尾, IL-6 and anti-inflammatory cytokines (IL-10) in serum of ARDS dogs (P0.05), and decreased the level of serum SP-A (P0.05). In lung tissue, SI could increase the expression of AQP-1,AQP-5 and FLIP mRNA (P0.05) and decrease the expression of IL-6mRNA (P0.05). There was no significant difference in the level of delayed inflammatory factor (HMGB1) in serum and lung tissue between the two groups. Conclusion SI can effectively improve oxygenation of ARDS, improve lung compliance and improve hypoxemia after closed sputum aspiration. The possible molecular biological mechanism is that SI alleviates the mechanical stimulation of alveolar epithelial cells and vascular endothelial cells by shear stress, inhibits the mRNA expression of inflammatory mediators in lung tissues, and reduces the release of systemic inflammatory mediators. The decreased secretion of inflammatory mediators alleviates the local inflammatory reaction and the injury of alveolar capillary barrier, decreases the loss of SP-A and the decrease of alveolar tension, thus preventing alveolar collapse. The damage of alveolar capillary barrier was alleviated, the expression of AQP-1 and AQP-5 in lung tissue increased, the ability of removing edema fluid was strengthened, the edema of alveolar and interstitial was alleviated, and oxygenation was improved. The production of inflammatory cytokines decreased and the expression of FLIP in lung tissue increased, which inhibited the apoptosis of pulmonary vascular endothelial cells and alveolar epithelial cells. Therefore, SI can reduce the secretion of inflammatory mediators, upregulate aquaporin and decrease the loss of SP-A in the lung, which may ultimately improve lung compliance and oxygenation.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R563.8

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