摘要
目的探讨白细胞介素10(IL-10)对急性肺损伤(ALI)大鼠炎症介质/抗炎介质表达的影响。方法向气道内滴注内毒素(LPS,10mg/kg)建立大鼠ALI模型。54只雄性SD大鼠随机分为对照组、LPS损伤组、LPS加IL-10组,每组18只,各组又分为2、6和24h3个亚组,每个亚组各6只。按各时间点观察大鼠动脉血氧分压(PaO2)、支气管肺泡灌洗液(BALF)中细胞总数及分类计数、肺系数、BALF总蛋白水平及肺病理,同时用逆转录聚合酶链反应(RTPCR)方法检测肺组织中炎症介质/抗炎介质的表达。结果1LPS损伤组大鼠PaO2呈进行性降低;肺系数、BALF总蛋白水平及BALF中细胞总数均明显增加,分类以中性粒细胞为主;肺病理示肺内中性粒细胞大量浸润,伴出血、透明膜形成。LPS加IL-10组的各项指标均较LPS损伤组减轻。2LPS损伤组肺组织肿瘤坏死因子-α(TNF-α)mRNA表达于2h达高峰,随后迅速下降;白细胞介素1β(IL1β)mRNA表达于2h显著升高,6h达高峰,随后迅速下降;IL-1受体拮抗剂(IL1ra)mRNA表达6h开始升高,且为峰值,24h仍高于对照组。LPS加IL10组肺组织TNF-αmRNA、IL-1βmRNA表达受抑,而IL-1ramRNA表达不受影响。结论1ALI早期TNFαmRNA、IL1βmRNA表达明显增加,而IL-1ramRNA表达滞后,提示在无外来干预情况下,ALI早期存在炎症介质/抗炎介质的失衡。
Objective To investigate the effects of interleukin10 (IL10) on expression of inflammatorymediators and antiinflammatory mediators during acute lung injury (ALI). Methods Rat model of ALI was reproduced by intratracheal instillation of lipopolysaccharide (LPS) in a dose of 10 mg/kg. Fiftyfourmale SD rats were randomly divided into control group, LPS group and LPS+IL10 group, with 18 rats in each group (6 rats at 2, 6 and 24 hours respectively). Arterial gas analysis, the total protein concentration in bronchoalveolar lavage fluid (BALF), the totalcell counts and classification in BALF, the lung coefficient, lung pathology were examined. Reverse transcriptionpolymerase chain reaction ( RTPCR ) method was used to determine the expression of tumor necrosis factorα (TNFα), interleukin1β (IL1β)and IL1ra mRNA in lung tissue. Results ①In LPS group the partial pressure of oxygen in artery (PaO_2) was progressively decreased, while the lung coefficient, the total protein concentration , the total cell counts in BALF were greatly increased, and lung pathology showed severe polymorphonuclearleukocytes infiltration with bleeding and hyaline membranes formation. In LPS+ IL10group the values of all above parameters were alleviated. ②In LPS group TNFα mRNA expression peakedat 2 hours, then decreased sharply; IL1β mRNA expression greatly increased at 2 hours , peaked at 6 hours , then decreased; IL1ra mRNA expression increased and peaked at 6 hours, remaininghigher than control group at 24 hours. IL10 inhibited TNFα mRNA and IL1β mRNA expressionbut showed no effecton IL1ra mRNA expression.Conclusion ①ALI is characterized by overwhelmingexpression of TNFαmRNA, IL1β mRNA, while the expression of IL1ra mRNA is much delayed than TNFα mRNAand IL1β mRNA. It suggests that there is an imbalance between inflammatory/antiinflammatory mediators in the early phase of ALI. ②IL10 can inhibit the expression of inflammatory mediators and has no effect on the expression of antiinflammatory mediators, thus it contributes to the balance between them, ameliorating ALI in rats.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2005年第6期338-341,i001,共5页
Chinese Critical Care Medicine
基金
国家科技部临床常见疾病诊治关键技术研究基金资助项目(9692006514)
