依达拉奉对烟雾吸入性损伤大鼠的肺保护作用
发布时间:2018-06-21 08:37
本文选题:烟雾吸入性损伤 + 依达拉奉 ; 参考:《天津医科大学》2013年硕士论文
【摘要】:研究背景: 吸入性损伤是由烟雾和(或)热力引起的肺实质和呼吸道的联合损伤,是烧伤患者早期死亡的主要原因之一。因其发病机制与某些炎症因子密切相关,可引起全身炎症反应综合征,继发其他脏器损伤,所以其在临床治疗上依然是一个难题。依达拉奉是一种新型强效的抗氧化剂,在抗炎症因子和清除氧自由基过程中发挥重要作用,本研究通过应用依达拉奉干预吸入性损伤的病理生理过程,观察其对肺功能的保护作用。 研究目的: 1.通过检测大鼠血清白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)含量水平,探讨依达拉奉对烟雾吸入性损伤早期炎症介质的影响。 2.通过检测大鼠肺组织匀浆中丙二醛(MDA)含量、髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)活性水平,探讨依达拉奉对烟雾吸入性损伤早期氧化/抗氧化因子的影响。 3.本研究通过观察依达拉奉对烟雾吸入性损伤后大鼠炎症介质以及氧化/抗氧化平衡的影响,探讨依达拉奉对早期烟雾吸入性损伤的肺保护作用及机制,为临床治疗吸入性损伤提供新思路。 研究方法: 将32只雄性Sprague-Dawle大鼠采用随机数字表法随机分为4组,每组8只。分别为正常对照组(A组),致伤空白组(B组),致伤依达拉奉治疗组(C组),致伤依达拉奉预防组(D组)。A组无处理,B组、C组、D组建立吸入性损伤模型。D组致伤前lOmin给予腹腔注射依达拉奉(9mg·kg-1),C组致伤后30min给予腹腔注射依达拉奉(9mg·kg-1),B组致伤后30min给予等量生理盐水。伤后6小时留取各组大鼠股动脉血液样本5ml离心取血清检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)含量,留取肺组织制备肺组织匀浆后测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)和肺髓过氧化物酶(MPO)活性。取部分右肺组织经4%甲醛溶液固定后做病理HE染色切片光镜观察。 结果: 1.一般情况观察及标本大体观察:一般情况:使用随机数字表法随机分组,各组间大鼠体重比较无统计学意义,所有致伤动物在致伤过程中无一例死亡,大鼠致伤后均出现呼吸急促,听诊肺部出现哮鸣音,心率加快,烦躁不安,放置室内空气流通地5-10分钟后上述症状逐渐消失。而空白对照组无呼吸急促及烦躁不安。活杀大鼠后取标本大体观察:空白对照组(A组)大鼠肺组织大致呈淡红色,无充血水肿;致伤空白组(B组)大鼠组织呈暗红色,明显充血水肿,部分肺组织有淤血;致伤依达拉奉治疗组(C组)大鼠肺组织部分充血水肿,有瘀斑;致伤依达拉奉预防组(D组)大鼠肺组织充血明显减轻,仅有少量出血点。 2.肺组织HE病理切片观察:光镜下空白对照组(A组)肺泡结构完整,肺泡壁均匀一致,肺泡腔少许渗液,无红白细胞渗出;致伤空白组(B组)肺泡间隔明显不均匀,肺间隔可见大量中性粒细胞浸润;致伤依达拉奉治疗组(C组)肺泡间隔中性粒细胞浸润减轻,肺泡间隔稍均匀;致伤依达拉奉预防组(D组)肺泡结构较清晰,肺泡间隔少量中性粒细胞浸润。 3.各组大鼠血清TNF-α,IL-6及IL-10的比较:与致伤空白组(B组)相比,致伤依达拉奉治疗组(C组)TNF-α、IL-6显著降低(P0.01),IL-10水平显著升高(P0.05),致伤依达拉奉预防组(D组)上述变化更明显(P0.01)。 4.各组大鼠肺组织匀浆MPO、MDA、SOD的比较:与致伤空白组(B组)相比,致伤依达拉奉治疗组(C组)MPO、MDA显著降低(P0.01),SOD水平显著升高(P0.05),致伤依达拉奉预防组(D组)上述变化更明显(P0.01)。 结论: 1.吸入性损伤后,肺组织明显充血水肿,肺泡结构破坏,肺泡间隔极不均匀,大量炎性细胞浸润。依达拉奉治疗组和预防组可以使上述损伤减轻,且预防组损伤减轻程度更加明显。 2.依达拉奉可能通过抗氧化和抑制炎症介质的作用对烟雾吸入性损伤后肺脏发挥保护作用,且预防性用药效果较好。
[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锛,
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