本文選題：急性肺損傷 + 全氟化碳　； 參考：《中國(guó)人民解放軍軍醫(yī)進(jìn)修學(xué)院》2012年博士論文

【摘要】：目的：經(jīng)汽化吸入全氟化碳(perfluorocarbon, PFC)治療內(nèi)毒素性急性肺損傷(acute lung injury, ALI)動(dòng)物模型,觀察汽化吸入PFC對(duì)ALI動(dòng)物表面活性蛋白和基質(zhì)金屬蛋白酶的影響。 方法：健康雌性新西蘭白兔24只(平均體重2.48±0.30kg),隨機(jī)分為4組：①急性肺損傷汽化吸入PFC治療組(ALI+PFC組)：通過(guò)靜脈注射脂多糖(lipopolysaccharide, LPS)(2.5mg/kg)制作急性肺損傷動(dòng)物模型,然后在常規(guī)機(jī)械通氣(容量控制f:40/min, FiO2:0.6, I:E1:1.5, PEEP5cmH2O)的基礎(chǔ)上,經(jīng)呼吸機(jī)吸氣管路以濕化器加熱PFC的方法給予汽化吸入PFC治療2小時(shí),然后繼續(xù)常規(guī)機(jī)械通氣6小時(shí)。②急性肺損傷組(ALI組)：制作急性肺損傷模型成功后給予常規(guī)機(jī)械通氣8小時(shí)。③汽化吸入PFC組(PFC組)：靜脈注射與LPS相同劑量的生理鹽水,在常規(guī)機(jī)械通氣基礎(chǔ)上,經(jīng)呼吸機(jī)吸氣管路以濕化器加熱PFC的方法給予汽化吸入PFC治療2小時(shí),然后繼續(xù)常規(guī)機(jī)械通氣6小時(shí)。④正常對(duì)照組(C組)：靜脈注射與LPS相同劑量的生理鹽水,然后給予常規(guī)機(jī)械通氣治療8小時(shí)。試驗(yàn)期間每隔1小時(shí)抽取靜脈血2ml和動(dòng)脈血1ml,試驗(yàn)結(jié)束后左肺進(jìn)行支氣管肺泡灌洗,留取右肺組織行病理檢查和分子生物學(xué)檢測(cè)。 第一部分：觀察各組動(dòng)物呼吸動(dòng)力學(xué)、血液動(dòng)力學(xué)、血?dú)夥治龅淖兓环謩e利用光學(xué)顯微鏡和透射電鏡觀察肺組織病理變化。 第二部分：①利用ELISA、real-time PCR和Wester-Blot技術(shù)檢測(cè)血漿、肺泡灌洗液和肺組織中SP-A、SP-B、SP-C、SP-D的表達(dá)情況；②利用real-time PCR和Wester-Blot技術(shù)檢測(cè)ErbB1、ErbB4和磷酸化ErbB1在肺組織中的表達(dá)情況。 第三部分：利用ELISA和real-time PCR技術(shù)檢測(cè)MMP-2、MMP-9及其抑制劑TIMP-1、TIMP-2在血漿、肺泡灌洗液和肺組織中表達(dá)情況。 結(jié)果： 1、ALI+PFC組較ALI組氧合指數(shù)升高,氣道阻力和病理?yè)p傷評(píng)分降低。PFC組較C組病理?yè)p傷評(píng)分降低。 2、①與ALI組比較,ALI+PFC組血漿中表面活性蛋白含量下降,肺泡灌洗液中SP-A、SP-B、SP-C含量增加,肺組織中SP-A、SP-B、SP-C mRNA表達(dá)增強(qiáng)。②與ALI組比較,ALI+PFC組肺組織中ErbB1和ErbB4mRNA表達(dá)減弱；與C組比較,PFC組肺組織中ErbB1和ErbB4mRNA表達(dá)增強(qiáng)。 3、與ALI組比較,ALI+PFC組血漿和肺泡灌洗液MMP-2、MMP-9的含量以及MMP-2/TIMP-2和MMP-9/TIMP-1降低,肺組織中MMP-2、MMP-9mRNA表達(dá)減弱。與C組比較,PFC組血漿中MMP-2、MMP-9的含量以及血漿和肺泡灌洗液中MMP-2/TIMP-2和MMP-9/TIMP-1降低。 結(jié)論： 1、汽化吸入PFC改善肺損傷可能與促進(jìn)SP-A、SP-B、SP-C的合成與分泌有關(guān)。汽化吸入PFC對(duì)SP-D的影響尚無(wú)法確定。也無(wú)法確定汽化吸入PFC對(duì)表面活性蛋白的影響是否與ErbB1和ErbB4有關(guān)。 2、抑制MMP-2、MMP-9的合成與分泌可能是汽化吸入PFC減輕急性肺損傷的作用機(jī)制之一。
[Abstract]:Objective: To observe the effects of vaporization of PFC on the surface active proteins and matrix metalloproteinases of ALI animals by vaporizing inhaled perfluorocarbon (PFC) in the treatment of acute lung injury (ALI).
Methods: 24 healthy female New Zealand white rabbits (average weight of 2.48 0.30kg) were randomly divided into 4 groups: (1) PFC treatment group (group ALI+PFC) with acute lung injury vaporization inhalation (group ALI+PFC): the animal model of acute lung injury was made by intravenous injection of lipopolysaccharide (2.5mg/kg) (2.5mg/kg), and then in conventional mechanical ventilation (volume control f:40/min, FiO2:0.6, On the basis of I:E1:1.5, PEEP5cmH2O), the inhalation inhalation PFC was given for 2 hours through the humidifier heating through the ventilator suction line. Then, the conventional mechanical ventilation was continued for 6 hours. Secondly, the acute lung injury group (group ALI): after making the acute lung injury model, the conventional mechanical ventilation was given for 8 hours. (3) vaporization inhalation PFC group (group PFC): static Intravenous injection of the same dosage of LPS saline, on the basis of conventional mechanical ventilation, on the basis of conventional mechanical ventilation, the method of heating PFC by the humidifier in the ventilator suction line for 2 hours, and then continuing the conventional mechanical ventilation for 6 hours. 4. Normal control group (group C): intravenous injection of the same dose of physiological saline with LPS, and then given the conventional machinery. The venous blood 2ml and arterial blood 1ml were taken every 1 hours during the test. After the test, the left lung was treated with bronchoalveolar lavage, and the right lung tissue was examined by pathological examination and molecular biological examination.
The first part: observe the changes of respiratory dynamics, hemodynamics and blood gas analysis in each group, and observe the pathological changes of lung tissue by optical microscope and transmission electron microscope respectively.
The second part: (1) the expression of SP-A, SP-B, SP-C, SP-D in plasma, alveolar lavage fluid and lung tissue was detected by ELISA, real-time PCR and Wester-Blot.
The third part: using ELISA and real-time PCR technology to detect the expression of MMP-2, MMP-9 and its inhibitor TIMP-1 and TIMP-2 in plasma, bronchoalveolar lavage fluid and lung tissue.
Result錛，

本文編號(hào)：1853800