依達(dá)拉奉對(duì)煙霧吸入性損傷大鼠的肺保護(hù)作用
發(fā)布時(shí)間:2018-06-21 08:37
本文選題:煙霧吸入性損傷 + 依達(dá)拉奉; 參考:《天津醫(yī)科大學(xué)》2013年碩士論文
【摘要】:研究背景: 吸入性損傷是由煙霧和(或)熱力引起的肺實(shí)質(zhì)和呼吸道的聯(lián)合損傷,是燒傷患者早期死亡的主要原因之一。因其發(fā)病機(jī)制與某些炎癥因子密切相關(guān),可引起全身炎癥反應(yīng)綜合征,繼發(fā)其他臟器損傷,所以其在臨床治療上依然是一個(gè)難題。依達(dá)拉奉是一種新型強(qiáng)效的抗氧化劑,在抗炎癥因子和清除氧自由基過程中發(fā)揮重要作用,本研究通過應(yīng)用依達(dá)拉奉干預(yù)吸入性損傷的病理生理過程,觀察其對(duì)肺功能的保護(hù)作用。 研究目的: 1.通過檢測(cè)大鼠血清白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-10(IL-10)、腫瘤壞死因子-α(TNF-α)含量水平,探討依達(dá)拉奉對(duì)煙霧吸入性損傷早期炎癥介質(zhì)的影響。 2.通過檢測(cè)大鼠肺組織勻漿中丙二醛(MDA)含量、髓過氧化物酶(MPO)和超氧化物歧化酶(SOD)活性水平,探討依達(dá)拉奉對(duì)煙霧吸入性損傷早期氧化/抗氧化因子的影響。 3.本研究通過觀察依達(dá)拉奉對(duì)煙霧吸入性損傷后大鼠炎癥介質(zhì)以及氧化/抗氧化平衡的影響,探討依達(dá)拉奉對(duì)早期煙霧吸入性損傷的肺保護(hù)作用及機(jī)制,為臨床治療吸入性損傷提供新思路。 研究方法: 將32只雄性Sprague-Dawle大鼠采用隨機(jī)數(shù)字表法隨機(jī)分為4組,每組8只。分別為正常對(duì)照組(A組),致傷空白組(B組),致傷依達(dá)拉奉治療組(C組),致傷依達(dá)拉奉預(yù)防組(D組)。A組無處理,B組、C組、D組建立吸入性損傷模型。D組致傷前l(fā)Omin給予腹腔注射依達(dá)拉奉(9mg·kg-1),C組致傷后30min給予腹腔注射依達(dá)拉奉(9mg·kg-1),B組致傷后30min給予等量生理鹽水。傷后6小時(shí)留取各組大鼠股動(dòng)脈血液樣本5ml離心取血清檢測(cè)腫瘤壞死因子-α(TNF-α)、白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-10(IL-10)含量,留取肺組織制備肺組織勻漿后測(cè)定丙二醛(MDA)含量、超氧化物歧化酶(SOD)和肺髓過氧化物酶(MPO)活性。取部分右肺組織經(jīng)4%甲醛溶液固定后做病理HE染色切片光鏡觀察。 結(jié)果: 1.一般情況觀察及標(biāo)本大體觀察:一般情況:使用隨機(jī)數(shù)字表法隨機(jī)分組,各組間大鼠體重比較無統(tǒng)計(jì)學(xué)意義,所有致傷動(dòng)物在致傷過程中無一例死亡,大鼠致傷后均出現(xiàn)呼吸急促,聽診肺部出現(xiàn)哮鳴音,心率加快,煩躁不安,放置室內(nèi)空氣流通地5-10分鐘后上述癥狀逐漸消失。而空白對(duì)照組無呼吸急促及煩躁不安。活殺大鼠后取標(biāo)本大體觀察:空白對(duì)照組(A組)大鼠肺組織大致呈淡紅色,無充血水腫;致傷空白組(B組)大鼠組織呈暗紅色,明顯充血水腫,部分肺組織有淤血;致傷依達(dá)拉奉治療組(C組)大鼠肺組織部分充血水腫,有瘀斑;致傷依達(dá)拉奉預(yù)防組(D組)大鼠肺組織充血明顯減輕,僅有少量出血點(diǎn)。 2.肺組織HE病理切片觀察:光鏡下空白對(duì)照組(A組)肺泡結(jié)構(gòu)完整,肺泡壁均勻一致,肺泡腔少許滲液,無紅白細(xì)胞滲出;致傷空白組(B組)肺泡間隔明顯不均勻,肺間隔可見大量中性粒細(xì)胞浸潤(rùn);致傷依達(dá)拉奉治療組(C組)肺泡間隔中性粒細(xì)胞浸潤(rùn)減輕,肺泡間隔稍均勻;致傷依達(dá)拉奉預(yù)防組(D組)肺泡結(jié)構(gòu)較清晰,肺泡間隔少量中性粒細(xì)胞浸潤(rùn)。 3.各組大鼠血清TNF-α,IL-6及IL-10的比較:與致傷空白組(B組)相比,致傷依達(dá)拉奉治療組(C組)TNF-α、IL-6顯著降低(P0.01),IL-10水平顯著升高(P0.05),致傷依達(dá)拉奉預(yù)防組(D組)上述變化更明顯(P0.01)。 4.各組大鼠肺組織勻漿MPO、MDA、SOD的比較:與致傷空白組(B組)相比,致傷依達(dá)拉奉治療組(C組)MPO、MDA顯著降低(P0.01),SOD水平顯著升高(P0.05),致傷依達(dá)拉奉預(yù)防組(D組)上述變化更明顯(P0.01)。 結(jié)論: 1.吸入性損傷后,肺組織明顯充血水腫,肺泡結(jié)構(gòu)破壞,肺泡間隔極不均勻,大量炎性細(xì)胞浸潤(rùn)。依達(dá)拉奉治療組和預(yù)防組可以使上述損傷減輕,且預(yù)防組損傷減輕程度更加明顯。 2.依達(dá)拉奉可能通過抗氧化和抑制炎癥介質(zhì)的作用對(duì)煙霧吸入性損傷后肺臟發(fā)揮保護(hù)作用,且預(yù)防性用藥效果較好。
[Abstract]:Research background:
Inhalation injury is a joint injury of lung parenchyma and respiratory tract caused by smoke and / or heat. It is one of the main causes of early death in burn patients. Because its pathogenesis is closely related to some inflammatory factors, it can cause systemic inflammatory response syndrome and secondary organ damage, so it is still a difficult problem in clinical treatment. Edaravone is a new potent antioxidants, play an important role in anti-inflammatory cytokines and oxygen free radical scavenging process, this study through the application of edaravone inhalation pathophysiological process of the injury, to observe the protective effect on lung function.
The purpose of the study is:
1. through the detection of serum interleukin -6 (IL-6), interleukin -10 (IL-10), tumor necrosis factor alpha (TNF- alpha) levels, to investigate the effect of edaravone early inflammatory mediators on smoke inhalation injury.
2. through the detection of rat lung tissue homogenate malondialdehyde (MDA) content, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity level, to explore the effect of inhalation injury of edaravone oxidant / antioxidant factor on the smoke.
3. by observing the effects of edaravone on the inflammatory mediators and oxidation / antioxidant balance in rats after smoke inhalation injury, the protective effects and mechanisms of edaravone on early smoke inhalation injury were explored to provide a new idea for clinical treatment of inhalation injury.
Research methods:
32 male Sprague-Dawle rats were randomly divided into 4 groups, 8 rats in each group, which were the normal control group (group A), the injury blank group (group B), the injured edaravone group (group C), the injured edaravone prevention group (D group).A group no treatment, B group, C group, and D group to establish the.D group before injuring lOmin intraperitoneal injection. Edaravone (9mg. Kg-1), group C was injected with edaravone (9mg. Kg-1) intraperitoneally after injury in group C, and 30min was given equal amount of physiological saline after injury in group B. 6 hours after injury, the blood samples of femoral artery in each group were left to take the blood samples from the femoral artery to detect tumor necrosis factor - alpha (TNF- a), -6 (IL-6), interleukin content and lung. Determination of content of tissue preparation of lung tissue homogenate (MDA) content, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity. The right lung tissue by Formaldehyde Solution in 4% after being fixed under light microscope HE staining.
Result錛,
本文編號(hào):2047915
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