机构地区:[1]山东省聊城市人民医院呼吸内科,252000 [2]河北医科大学第一医院呼吸科,石家庄050031 [3]河北医科大学第一医院血液科,石家庄050031 [4]河北医科大学第一医院急诊科,石家庄050031 [5]天津市第三中心医院儿科,300170 [6]浙江省苍南县人民医院内科,温州325800 [7]河北省老年病医院呼吸科,石家庄050031
出 处:《国际呼吸杂志》2017年第5期330-335,共6页International Journal of Respiration
摘 要:目的 观察辛伐他汀对吸烟所致COPD大鼠肺组织中IL-17、IL-21及转录因子视黄酸相关孤儿受体γt (retinoid-related orphan nuclear receptor gamma t,RORγt)表达的影响,探讨辛伐他汀治疗COPD的价值及其作用机制.方法 SD雄性大鼠随机分为对照组(10只)、吸烟组(11只)及治疗组(10只);观察各组大鼠肺组织的病理改变,采用免疫组织化学方法对大鼠肺组织IL-17、IL-21及RORγt蛋白的分布进行检测;Real time RT-PCR方法对肺组织中IL-17、IL-21及RORγtmRNA的表达进行测定.结果 在支气管黏膜上皮和肺泡间隔内,IL-17、IL-21及RORγt阳性细胞在吸烟组[(90.00±14.02) cells/mm2、(61.18±9.16) cells/mm2、(77.27±7.95) cells/mm2]和治疗组[(72.80±10.79) cells/mm2、(49.40±3.34) cells/mm2、(65.40±5.23) cells/mm2]的表达量均高于对照组[(5.20±4.49) cells/mm2、(8.20±3.16) cells/mm2、(6.80±5.85) cells/mm2] (P<0.01);且吸烟组的表达量高于治疗组(P<0.05).肺组织中IL-17、IL-21及RORγt mRNA的表达吸烟组(7.49±2.93、12.22±4.98、4.04±0.21)和治疗组(2.39±0.62、3.78±0.35、1.76±0.25)均高于对照组(1.00±0.00、1.00±0.00、1.00±0.00)(P<0.01),吸烟组的表达量高于治疗组(P<0.05).肺泡间隔内的IL-17阳性细胞数与平均内衬间隔呈正相关(r=0.729,P<0.01),与平均肺泡数呈负相关(r =-0.889,P<0.01).结论 IL-17、IL-21和RORγt在大鼠COPD形成过程中起着一定的作用,辛伐他汀降低大鼠肺内炎症细胞及炎症因子IL-17、IL-21及RORγt的表达,这种作用是辛伐他汀抑制COPD大鼠肺组织炎症反应和肺病理改变的机制之一.Objective To observe the effects of simvastatin on smoking induced COPD in the lung tissues of rats with IL-17,IL-21 and retinoid-related orphan nuclear receptor gamma t (ROR γ t) expression,to explore the value of simvastatin in the treatment of COPD and its mechanism.Methods Male SD rats were randomly divided into three groups:control group (n =10),smoking group (n =11) and treatment group (n =10).The pathological changes of lung tissue were observed in each group.The distribution of IL-17,IL-21 and RORγt protein in lung tissue of rats were detected by immunohistochemical method.The mRNA expression of IL-17,IL-21 and RORγt in rat lung tissue was measured by real-time RT-PCR.Results In the bronchial epithelium and alveolar septa,the expression of ID17,IL-21 and RORγt positive cells were higher in smoking group [(90.00 ± 14.02) cells/mm2,(61.18 ± 9.16) cells/mm2,(77.27 ± 7.95) cells/mm2] and treatment group [(72.80 ± 10.79) cells/mm2,(49.40 ± 3.34) cells/mm2,(65.40 ± 5.23) cells/mm2] compared with control group [(5.20 ± 4.49) cells/mm2,(8.20 ± 3.16) cells/mm2,(6.80 ± 5.85) cells/mm2] (P 〈 0.01),and the expression of smoking group was higher than the treatment group (P 〈0.05).The mRNA expression of IL-17,IL-21 and RORγt in lung tissue of smoking group (7.49 ± 2.93,12.22 ± 4.98,4.04 ± 0.21) and treatment group (2.39 ± 0.62,3.78 ± 0.35,1.76 ± 0.25) were higher than those in control group (1.00 ± 0.00,1.00 ± 0.00,1.00 ± 0.00) (P 〈0.01),and the expression level in smoking group was higher than that in control group (P 〈 0.05).There was a positive correlation between the number of IL-17 positive cells in the alveolar septum and the mean linear intercept (r =0.729,P 〈0.01),which was negatively correlated with the mean alveolar number (r =-0.889,P 〈0.01).Conclusions IL-17,IL-21 and RORγt plays a role in the process of COPD formation in rats,simvastatin reduced expression of inflammatory cells and
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