儿童肺炎支原体肺炎血清中细胞因子含量变化及其对气管张力的影响

发布时间：2018-10-26 07:17

【摘要】：目的:调查病情严重程度不同MPP患者血清中细胞因子(IL-8、18、10)含量的变化及其相应的临床炎症指标(CRP、LDH)之间的相关性,探讨炎症因子在MPP、尤其SMPP发病中作用。方法:募集自2013年3月~2015年2月安徽医科大学第一附属医院儿科门诊及同期呼吸病房共66例儿童为研究对象,对照组32例(健康儿童),实验组34例(儿童MPP患者)。其中实验组又分为轻症MPP无合并哮喘组(Group 1);重症MPP无合并哮喘组(Group 2);轻症MPP合并哮喘组(Group 3),检测两组、实验组内细胞因子含量及相应炎症指标。同时收集临床资料包括:性别、年龄、LDH、CRP、血常规(淋巴细胞、中性粒细胞)等,比较分析对照组与实验组以及实验组间血清样本中细胞因子含量变化及相应临床炎症指标之间的相关性,用ELISA法测定细胞因子水平。结果:(1)与对照组比较,实验组血清细胞因子(IL-8、IL-10、IL-18)水平显著升高,差异有统计学意义(P=0.044、0.001、0.001)。(2)与治疗前比较,实验组血清中细胞因子IL-18和CRP在治疗后下降,差异有统计学意义(P=0.020和0.001)。(3)与Group1比较,Group 2细胞因子IL-8水平增高,差异无统计学意义(P=0.232);与Group1比较,Group 2细胞因子IL-18水平增高,差异具有统计学意义(P0.05);与Group1比较,Group 2细胞因子IL-10水平降低,差异有统计学意义(P0.05)。(4)细胞因子与CRP之间的相关性:IL-8和IL-18与CRP有正相关性,(R=0.467和0.619,P0.001,0.05)。IL-10与CRP之间无相关性(R=0.223,P=0.058)。结论:细胞因子IL-8、IL-18和IL-10参与MPP中炎症反应,IL-10在MPP发病炎症中发挥双向调节作用,IL-10水平可作为MPP严重炎症预测指标之一,控制炎症在MPP尤其SMPP治疗中至关重要。目的:本研究拟通过动物实验阐明TNF-α或IL-8在激动剂引起的小鼠气管平滑肌收缩中的效应,进一步验证细胞因子在MPP发病中作用机制。方法:实验采用小鼠气管离体培养,通过TNF-α或IL-8孵育小鼠气管18小时后,利用张力测定系统检测激动剂引起的气管平滑肌张力的变化,旨在揭示TNF-α和IL-8对小鼠气管平滑肌VDCC介导的钙内流的影响,并进一步探讨VDCC蛋白表达水平变化及其对气管张力的影响。结果:通过研究发现:(1)TNF-α和IL-8预处理可以显著增强高钾和卡巴胆碱引起的小鼠气管收缩性;(2)VDCC通道阻断剂可以显著阻断TNF-α和IL-8预处理引起的小鼠气管收缩增强作用;(3)蛋白免疫印迹实验发现,TNF-α和IL-8预处理显著增强了小鼠气管VDCC的表达。结论:炎症因子可通过增强气管平滑肌细胞VDCC的表达,增强其对收缩剂的收缩反应,从而可能导致气管痉挛和呼吸功能障碍。该研究有助于了解炎症因子在MPP发病中的可能作用和机制,为将来的治疗提供一定的理论依据,为临床治疗提供潜在的、新的治疗方法。
[Abstract]:Objective: to investigate the changes of serum cytokine (IL-8,18,10) levels in patients with MPP with different severity of disease and the correlation between the corresponding clinical inflammatory markers (CRP,LDH), and to explore the role of inflammatory factors in the pathogenesis of MPP, especially SMPP. Methods: from March 2013 to February 2015, 66 children in pediatrics outpatient department and respiratory ward of the first affiliated Hospital of Anhui Medical University were recruited, 32 healthy children in control group and 34 MPP patients in experimental group. The experimental group was divided into three groups: mild MPP without asthma (Group 1), severe MPP without asthma (Group 2) and mild MPP with asthma (Group 3). Clinical data including sex, age, LDH,CRP, blood test (lymphocytes, neutrophils) were also collected. The levels of cytokines in serum samples of the control group, the experimental group and the corresponding clinical inflammatory indexes were compared and analyzed. The levels of cytokines were measured by ELISA method. Results: (1) compared with the control group, the level of serum cytokine (IL-8,IL-10,IL-18) in the experimental group was significantly higher than that in the control group (P < 0.04 卤0.001 / 0. 001). (2). The levels of serum cytokines IL-18 and CRP in the experimental group were significantly decreased after treatment (P0. 020 and 0.001). (3). Compared with Group1, the level of Group 2 cytokine IL-8 was increased, but there was no significant difference (P0. 232). Compared with Group1, the level of Group 2 cytokine IL-18 increased, the difference was statistically significant (P0.05). Compared with Group1, the level of Group 2 cytokine IL-10 was significantly lower than that of Group1 (P0.05). (4) the correlation between cytokines and CRP: IL-8 and IL-18 were positively correlated with CRP (RP0. 467 and 0. 619, P < 0. 05). There was no correlation between IL-10 and CRP. Conclusion: cytokines IL-8,IL-18 and IL-10 are involved in the inflammatory reaction in MPP, and IL-10 plays a bidirectional role in the pathogenesis of MPP. IL-10 level can be used as one of the predictors of severe inflammation of MPP. Controlling inflammation is essential in MPP, especially in the treatment of SMPP. Aim: to elucidate the effects of TNF- 伪 or IL-8 on the contraction of tracheal smooth muscle in mice induced by agonists in order to further verify the role of cytokines in the pathogenesis of MPP. Methods: the mouse trachea was cultured in vitro and incubated with TNF- 伪 or IL-8 for 18 hours. The tension of tracheal smooth muscle induced by agonist was measured by tension measurement system. The aim of this study was to investigate the effects of TNF- 伪 and IL-8 on the calcium influx mediated by VDCC in the tracheal smooth muscle of mice, and to further explore the changes of VDCC protein expression and its effect on tracheal tension. Results: (1) TNF- 伪 and IL-8 pretreatment could significantly enhance tracheal contraction induced by high potassium and carbachol in mice. (2) VDCC channel blockers could significantly block the enhancement of tracheal contraction induced by TNF- 伪 and IL-8 pretreatment in mice. (3) Western blot analysis showed that TNF- 伪 and IL-8 pretreatment significantly enhanced the expression of VDCC in the trachea of mice. Conclusion: inflammatory factors may enhance the contractile response of tracheal smooth muscle cells by enhancing the expression of VDCC, which may lead to tracheal spasm and respiratory dysfunction. This study is helpful to understand the possible role and mechanism of inflammatory factors in the pathogenesis of MPP, to provide some theoretical basis for future treatment, and to provide potential and new treatment methods for clinical treatment.
【学位授予单位】：安徽医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R725.6

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