廖小红　张毅靖　唐洪梅　丘振文　罗丹冬　杨柳柳　杨丽娥　罗骞

中图分类号 R285.5 文献标志码 A 文章编号 1001-0408（2021）21-2593-06

DOI 10.6039/j.issn.1001-0408.2021.21.06

摘 要 目的：研究苇茎汤对慢性阻塞性肺疾病急性加重期（AECOPD）模型大鼠的改善作用及可能机制。方法：将55只雄性SD大鼠按随机数字表法随机分为正常组，模型组，苇茎汤低、高剂量组（8.37、16.74 g/kg，以生药量计）和地塞米松组（阳性对照组，0.09 mg/kg），每组11只。除正常组外，其余各组大鼠均采用香烟联合脂多糖诱导的方法建立AECOPD模型。造模结束后，正常组和模型组大鼠灌胃水，其余各组大鼠灌胃相应药物，每天灌胃2次，连续14 d。末次灌胃后，测定大鼠血清中白细胞介素1β（IL-1β）水平，观察大鼠肺组织和支气管的病理学变化，测定大鼠肺组织中基质金属蛋白酶9 （MMP-9）、基质金属蛋白酶抑制剂1（TIMP-1） mRNA表达水平及Ras同源基因家族成员A（RhoA）、蓬乱蛋白相关形态形成活化因子1（DAAM1）和细胞增殖抑制基因（HSG）蛋白的表达水平。结果：与正常组比较，模型组大鼠血清中IL-1β水平以及肺组织中MMP-9、TIMP-1 mRNA表达水平和RhoA、DAAM1蛋白表达水平均显著升高（P<0.05），肺组织中HSG蛋白表达水平显著降低（P<0.05）;支气管周围有较多慢性炎症细胞浸润，部分气道黏膜上皮脱落;肺泡代偿性扩张，肺间隔毛细血管扩张、充血。与模型组比较，苇茎汤高剂量组大鼠血清中IL-1β水平和肺组织中MMP-9 、TIMP-1 mRNA表达水平均显著降低（P<0.05）;苇茎汤低、高剂量组大鼠肺组织中RhoA、DAAM1蛋白表达水平均显著降低（P<0.05），HSG蛋白表达水平均显著升高（P<0.05）;苇茎汤高剂量组大鼠支气管周围炎症细胞浸润、气道黏膜脱落等病理形态学变化均得到明显改善，肺泡上皮结构较完整、未见明显肺扩张。结论：苇茎汤对AECOPD模型大鼠具有一定的改善作用;其机制可能与下调肺组织中MMP-9、TIMP-1 mRNA和RhoA、DAAM1蛋白的表达，上调肺组织中HSG蛋白的表达，从而抑制气道重建有关。

关键词 慢性阻塞性肺疾病急性加重期;苇茎汤;細胞增殖抑制基因;Wnt信号通路;大鼠

ABSTRACT   OBJECTIVE： To study the improvement effects of Weijing decoction on AECOPD model rats and its possibile mechanism. METHODS：Totally 55 male SD rats were randomly divided into normal group， model group， Weijing decoction low-dose and high-dose groups （8.37， 16.74 g/kg， by crude drug），dexamethasone group （positive control group，0.09 mg/kg），with 11 rats in each group. Except for normal group， AECOPD model was induced by cigarettes combined with lipopolysaccharide in other groups. After modeling， normal group and model group were given constant volume of water intragastrically，and other groups were given relevant medicine intragastrocally，twice a day，for 14 days. After last intragastric administration， the serum level of IL-1β was determined， and pathological changes of lung tissue and bronchus were observed in each group; mRNA expression of MMP-9 and TIMP-1 genes in lung tissue were detected; protein expression of Ras homologous gene family member （RhoA），dishevelled associated activator of morphogenesis-1 （DAAM1） and hyperplasic suppress gene （HSG） in lung tissue were also determined. RESULTS： Compared with normal group， the levels of IL-1β in serum， mRNA expression of  MMP-9 and TIMP-1 as well as protein expression of RhoA and DAAM1 in lung tissue were increased significantly in the model group （P<0.05）， while protein expression of HSG in lung tissue was decreased significantly （P<0.05）;there were many chronic inflammatory cells infiltrating around the bronchus，some airway mucosa epithelium exfoliating，alveolar compensatory dilation，pulmonary septal capillary dilation and hyperemia. Compared with model group， the levels of IL-1β in serum， mRNA expression of MMP-9 and TIMP-1 in lung tissue were decreased significantly in Weijing decoction high-dose group （P<0.05）; the protein expression of RhoA and DAAM1 in lung tissue were decreased significantly in Weijing decoction low-dose and high-dose groups （P<0.05），while the protein expression of HSG in lung tissue was increased （P<0.05）; the pathological changes of Weijing decoction high-dose group， such as inflammatory cells infiltrating around the bronchus and shedding of airway mucosa， were improved significantly， and there was complete alveolar epithelium structure but no obvious pulmonary dilation. CONCLUSIONS： Weijing decoction can improve AECOPD model rats to certain extent; its mechanism may be associated with down-regulating mRNA expression of MMP-9 and TIMP-1 as well as protein expression of RhoA and DAAM1 in lung tissue， up-regulating protein expression of HSG in lung tissue so as to inhibit the airway remodeling.

KEYWORDS   Acute exacerbation of chronic obstructive pulmonary disease; Weijing decoction; Hyperplasic suppress gene; Wnt signaling pathway;Rat

慢性阻塞性肺疾病（COPD）是一种以肺功能障碍和持续的气流受限为特征的阻塞性肺疾病，主要症状为咳嗽和呼吸困难[1]。在COPD 病程进展中，气道重建是关键，其实质是小气道成纤维细胞的增生[2]。COPD的发生与长期吸烟和吸入灰尘、毒素等因素相关[3-4]，其中长期吸烟是COPD的主要诱因，大部分COPD患者都有较长的吸烟史[5-6]。COPD分为稳定期和急性加重期（AECOPD），AECOPD患者的呼吸系统症状加重且明显高于日常水平，此时亟待调整临床治疗方案[7]。……