Cao Lihua, Chen Yu, Zhao Yue, Zhang Hongyan, Wang Shengli, Wang Zhenshan, Kang Jian
Institute of Respiratory Disease, First Affiliated Hospital, China Medical University, Shenyang, China.
Arzneimittelforschung. 2011;61(12):685-92. doi: 10.1055/s-0031-1300588.
This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divided into 6 groups: control (n = 6), exposure to cigarette smoke (CS, n = 6), CS plus Myrtol standardized treatment (CS + M, n = 6), Pseudomonas aeruginosa (PA) infection (PA, n = 25), CS + PA (n = 25), and CS + PA + M (n = 25). For all 62 CS rats, they were exposed to cigarette smoke for a period of 12 weeks. During this time period the 31 CS + M rats (CS + M; CS + PA + M) received 300 mg/kg/day Myrtol standardized intragastrically always 30 min prior to smoke exposure. For CS + PA and CS + PA + M rats, intratracheal PA inoculation was performed after the 12 weeks of smoke exposure. All intratracheal PA inoculations were followed by a post-infection examination at 6, 12, 24, 48 and 72 h in each 5 rats. All study animals were euthanized and their lungs were excised; the left lung was homogenized for determination of bacterial load and measurements of TNF-alpha and IL-6, the right lungs were preserved for histo- and immunohistochemical examinations (e. g. MUC5AC). The lungs from CS rats were pathologically similar to those of COPD patients with the characteristics of goblet cell metaplasia and MUC5AC hypersecretion. CS animals had a significantly greater number of MUC5AC positive cells in the bronchial epithelial cells, and significantly increased expression levels of TNF-alpha and IL-6 after PA infection. However, the administration of Myrtol standardized significantly (p = 0.002) attenuated MUC5AC hypersecretion, measured as integrity optical density (IOD), in CS + M rats (45.98 +/- 6.25) as compared to CS alone (65.55 +/- 11.18) rats. The same applies at different time points between CS + PA rats (65.15 +/- 11.94, 75.88 +/- 7.42, 81.2 +/- 6.49, 75.14 +/- 6.85 and 67.32 +/- 10.61, respectively) and CS + PA + M rats (47.08 +/- 4.78, 54.22 +/- 6.59, 65.4 +/- 6.12, 59.98 +/- 4.96 and 48.43 +/- 7.29, respectively). Similar effects were found in the production of IL-6 and TNF-alpha in the CS + PA + M lungs. Similarly the bacterial load of 10,980 +/- 4,253 CFU in CS + PA + M was significantly lower compared to 42,400 +/- 3,296 CFU in CS + PA lungs after 72 h PA infection. In conclusion, this experimental study demonstrates a significant therapeutic effect of Myrtol standardized in treating common pathological conditions, such as airway mucus hypersecretion and defect of mucociliary functions in COPD.
本研究旨在探讨标准桃金娘油（吉诺通强力型）在慢性阻塞性肺疾病（COPD）动物模型中的治疗效果。总共93只实验大鼠被随机分为6组：对照组（n = 6）、暴露于香烟烟雾组（CS，n = 6）、CS加标准桃金娘油治疗组（CS + M，n = 6）、铜绿假单胞菌（PA）感染组（PA，n = 25）、CS + PA组（n = 25）以及CS + PA + M组（n = 25）。对于所有62只CS大鼠，使其暴露于香烟烟雾中12周。在此期间，31只CS + M大鼠（CS + M组；CS + PA + M组）在每次烟雾暴露前30分钟经胃内给予300 mg/kg/天的标准桃金娘油。对于CS + PA和CS + PA + M大鼠，在烟雾暴露12周后进行气管内PA接种。所有气管内PA接种后，对每组5只大鼠在感染后6、12、24、48和72小时进行感染后检查。所有研究动物均实施安乐死并切除其肺脏；将左肺匀浆以测定细菌载量以及测量肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），右肺则留作组织学和免疫组织化学检查（如MUC5AC）。CS大鼠的肺脏在病理上与COPD患者的肺脏相似，具有杯状细胞化生和MUC5AC分泌过多的特征。CS组动物支气管上皮细胞中MUC5AC阳性细胞数量显著更多，并且在PA感染后TNF-α和IL-6的表达水平显著升高。然而，与单独的CS组大鼠（65.55±11.18）相比，标准桃金娘油的给药显著（p = 0.002）减轻了CS + M组大鼠以积分光密度（IOD）衡量的MUC5AC分泌过多情况（45.98±6.25）。CS + PA组大鼠（分别为65.15±11.94、75.88±7.42、81.2±6.49、75.14±6.85和67.32±10.61）与CS + PA + M组大鼠（分别为47.08±4.78、54.22±6.59、65.4±6.12、59.98±4.96和48.43±7.29）在不同时间点的情况相同。在CS + PA + M组肺脏中IL-6和TNF-α的产生方面也发现了类似效果。同样，在PA感染72小时后，CS + PA + M组的细菌载量为10,980±4,253 CFU，与CS + PA组肺脏中的42,400±3,296 CFU相比显著更低。总之，本实验研究证明标准桃金娘油在治疗COPD常见病理状况（如气道黏液分泌过多和黏液纤毛功能缺陷）方面具有显著的治疗效果。
