温肺合剂对闭塞性细支气管炎模型大鼠肺组织纤维化和半胱氨酰白三烯受体1表达的影响
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摘要
目的:探讨温肺合剂对闭塞性细支气管炎(BO)模型大鼠肺组织纤维化和半胱氨酰白三烯受体1(CysLTR-1)表达的影响。方法:将200只大鼠随机分为正常组、模型制备组,BO造模结束后将模型制备组大鼠随机分为模型组、温肺合剂低、中、高剂量组和地塞米松+孟鲁司特钠组。正常组、模型组按大鼠处死时间点分为第7天、第14天、第21天、第28天,药物干预组按处死时间点分为第14天、第21天、第28天,每个亚组10只大鼠。比较各组大鼠肺系数变化情况判断肺纤维化情况;采用HE染色观察大鼠肺组织炎症及纤维损伤结果;采用蛋白质免疫印迹法观察肺组织CysLTR-1表达水平。结果:温肺合剂中、高剂量组和地塞米松+孟鲁司特钠组肺系数显著低于模型组(P<0.01)。HE染色观察肺组织病理发现,药物干预各组实验前期病理表现与模型组类似,后期温肺合剂中、高剂量组纤维化程度小于温肺合剂低剂量组和地塞米松+孟鲁司特钠组。模型组CysLTR-1表达水平显著高于正常组(P<0.01)。温肺合剂高剂量组和地塞米松+孟鲁司特钠组各时间点CysLTR-1表达水平均显著低于模型组(P<0.01),且两者之间比较差异无统计学意义(P>0.05)。结论:温肺合剂可抑制闭塞性细支气管炎模型大鼠肺组织CysLTR-1的表达,阻断CysLTs介导的炎症及纤维化。
Objective: To investigate the effect of Wenfei mixture on pulmonary fibrosis and the expression of cysteinyl leukotriene receptor 1(CysLTR-1) in rats with bronchiolitis obliterans(BO) model. Methods:A total of 200 rats were randomly divided into normal group, model preparation group, and the model preparation group rats were then randomly divided into subgroups of model, low-dose of Wenfei mixture, middle-dose of Wenfei mixture, high-dose of Wenfei mixture and dexamethasone+montelukast. Normal group and model group rats were killed according to the time points for seventh days, fourteenth days, twenty-first days,twenty-eighth days and drug intervention group according to the time point of fourteenth days, twenty-first days, twenty-eighth days, with 10 rats in each sub group. Pulmonary fibrosis was determined by comparing the change of lung coefficient in each group. The results of inflammation and fiber damage in lung tissue were observed by HE staining; and the expression of CysLTR-1 in lung tissue was observed by Western blot.Results: Compared with the model group, the lung coefficient of Wenfei mixture group, Wenfei mixturegroup and dexamethasone+montelukast group were significantly lower, and the difference was statistically significant(P<0.01). Observation of lung tissue HE staining, pathological manifestations of early experimental drug intervention groups was similar to that of the model group. In the later stage, the degree of fibrosis in middle and high dose of Wenfei mixture group is less than that in the low dose group of Wenfei mixture and dexamethasone+montelukast group. The expression level of CysLTR-1 in model group was significantly higher than that in normal group(P<0.01). The expression level of CysLTR-1 in the high dose group and dexamethasone+montelukast group at each time point was significantly lower than that in the model group(P<0.01), and there was no significant difference between the two groups(P>0.05). Conclusion: Wenfei mixture may play an important role in the treatment of BO by inhibiting the expression of CysLTR-1 and consequently blockading inflammation.
Objective: To investigate the effect of Wenfei mixture on pulmonary fibrosis and the expression of cysteinyl leukotriene receptor 1(CysLTR-1) in rats with bronchiolitis obliterans(BO) model. Methods:A total of 200 rats were randomly divided into normal group, model preparation group, and the model preparation group rats were then randomly divided into subgroups of model, low-dose of Wenfei mixture, middle-dose of Wenfei mixture, high-dose of Wenfei mixture and dexamethasone+montelukast. Normal group and model group rats were killed according to the time points for seventh days, fourteenth days, twenty-first days,twenty-eighth days and drug intervention group according to the time point of fourteenth days, twenty-first days, twenty-eighth days, with 10 rats in each sub group. Pulmonary fibrosis was determined by comparing the change of lung coefficient in each group. The results of inflammation and fiber damage in lung tissue were observed by HE staining; and the expression of CysLTR-1 in lung tissue was observed by Western blot.Results: Compared with the model group, the lung coefficient of Wenfei mixture group, Wenfei mixturegroup and dexamethasone+montelukast group were significantly lower, and the difference was statistically significant(P<0.01). Observation of lung tissue HE staining, pathological manifestations of early experimental drug intervention groups was similar to that of the model group. In the later stage, the degree of fibrosis in middle and high dose of Wenfei mixture group is less than that in the low dose group of Wenfei mixture and dexamethasone+montelukast group. The expression level of CysLTR-1 in model group was significantly higher than that in normal group(P<0.01). The expression level of CysLTR-1 in the high dose group and dexamethasone+montelukast group at each time point was significantly lower than that in the model group(P<0.01), and there was no significant difference between the two groups(P>0.05). Conclusion: Wenfei mixture may play an important role in the treatment of BO by inhibiting the expression of CysLTR-1 and consequently blockading inflammation.
引文
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[7]张永菊,张会武,孟秋云,等.匹多莫德联合孟鲁司特对闭塞性细支气管炎患儿T细胞亚群的影响观察[J].药物流行病学杂志,2016,25(8):473-476.
[8]卢立伟.儿童闭塞性细支气管炎中医证型分布规律及温肺合剂对模型鼠CCSP、PPARγ、TGF-β1/Smad3影响的研究[D].济南:山东中医药大学,2016.
[9]周艳华,隋宇,孙明杰.精制清开灵注射液对大鼠肺纤维化组织学变化的影响[J].中国中医基础医学杂志,2006,12(7):528-529.
[2]郭志华,刘勇谋,李桂梅.闭塞性细支气管炎误诊报告并文献复习[J].临床误诊误治,2016,29(2):44-46.
[3]尹嘉宁.BO小鼠模型的建立及儿童感染后BO的前瞻性分析[D].长春:吉林大学,2016.
[4]Kurland G,Michelson P.Bronchiolitis Obliterans in Children[J].Pediatric Pulmonology,2005,39(3):193-208.
[5]朱美华,梁敏,王志坚,等.Cys LTR-1和Cys LTR-2在腺样体肥大儿童腺样体组织中的表达[J].中国当代儿科杂志,2015,17(2):159-163.
[6]Singh RK,Gupta S,Dastidar S,et al.Cysteinyl leukotrienes and their receptors:molecular and functional characteristics[J].Pharmacology,2010,85(6):336-349.
[7]张永菊,张会武,孟秋云,等.匹多莫德联合孟鲁司特对闭塞性细支气管炎患儿T细胞亚群的影响观察[J].药物流行病学杂志,2016,25(8):473-476.
[8]卢立伟.儿童闭塞性细支气管炎中医证型分布规律及温肺合剂对模型鼠CCSP、PPARγ、TGF-β1/Smad3影响的研究[D].济南:山东中医药大学,2016.
[9]周艳华,隋宇,孙明杰.精制清开灵注射液对大鼠肺纤维化组织学变化的影响[J].中国中医基础医学杂志,2006,12(7):528-529.