摘要
目的:通过观察慢性阻塞性肺疾病大鼠治疗前后气道病理的改变,分析中医药治疗慢性阻塞性肺疾病的可能机制。方法:实验于2005-04/2005-10山东中医药大学附属医院中心实验室进行。①健康雄性SPF级Wistar大鼠264只,随机数字表法分为以下11组:空白对照组,寒痰蕴肺模型组和治疗组,痰热阻肺模型组和治疗组,肺气虚模型组和治疗组,脾气虚模型组和治疗组,肾气虚模型组和治疗组,每组24只。采用改良烟熏加气管滴加脂多糖方法复制慢性阻塞性肺疾病模型,并根据分型,分别给予不同干预,进行二次造模。②第30天起各治疗组分别灌服相应证型的预治疗中药合剂,连续14d。寒痰蕴肺治疗组灌服小青龙汤煎剂(麻黄9g,桂枝6g,白芍9g,干姜3g,五味子3g,半夏9g,甘草6g,细辛3g,水煎浓缩为浓度0.6g/mL的浓缩液),痰热阻肺治疗组大鼠灌服麻杏石甘汤煎剂(麻黄5g,杏仁9g,甘草6g,石膏18g,水煎浓缩为浓度0.475g/mL的浓缩液),肺气虚治疗组灌服玉屏风散煎剂(防风3g,黄芪3g,白术6g,水煎浓缩为浓度0.15g/mL的浓缩液),脾气虚治疗组灌服六君子汤煎剂(人参9g,白术9g,茯苓9g,炙甘草6g,半夏12g,陈皮9g,水煎浓缩为浓度0.675g/mL的浓缩液),肾气虚治疗组灌服人参蛤蚧散煎剂(蛤蚧6g,杏仁15g,甘草15g,人参6g,茯苓6g,贝母6g,桑白皮6g,知母6g,除蛤蚧外其他药物水煎浓缩为浓度0.75g/mL的浓缩液,蛤蚧研末兑入),2mL/d,相当于成人剂量的7.5倍(饮片由山东中医药大学附属医院中药房提供)。模型组大鼠每天给与2mL生理盐水灌胃。空白对照组不做任何干预,相同室内环境下自由饮食饮水。③光镜下观察大鼠小气道病理改变,电镜下观察大鼠气管纤毛的变化,并按照小气道病变评估方法和标准进行分析描述。结果:实验过程中,各造模组均有大鼠死亡,最终进入结果分析242只。①正常对照组中、小支气管黏膜上皮细胞排列整齐,肺泡结构连续,肺泡壁完整,且未见明显渗出。模型组气道黏膜充血水肿,上皮细胞变性坏死糜烂脱落,肺内细支气管、终末细支气管管腔及周围表现出不同程度的慢性炎性细胞浸润,管壁周围平滑肌和纤维细胞增生、断裂;肺泡管、肺泡囊及肺泡明显扩大,间隔变薄、断裂,肺泡扩大融合;小动脉血管壁增厚,平滑肌增生,管腔变小,周围炎性细胞浸润。②光镜、电镜下观察治疗组与模型组相比纤毛粘连倒伏、上皮细胞变性坏死以及炎细胞浸润等现象表现均明显减轻,肺大泡数量减少。结论:各经典方剂通过辨证论治均可以缓解大鼠肺内细支气管、终末细支气管管腔及周围表现炎性细胞浸润及分泌物阻塞,恢复纤毛粘连、倒伏、脱落,改善气道高反应性和气道重塑,对于慢性阻塞性肺疾病气道的修复和炎症的缓解作用。
AIM： To observe the pathological changes of airway in rats with chronic obstructive pulmonary diseases （COPD）, and analyze the possible mechanism of traditional Chinese medicine （TCM） prescription in the treatment of COPD. METHODS： The experiment was carried out in the Central Laboratory, Affiliated Hospital of Shandong University of TCM from April to October in 2005.①A total of 264 healthy male Wistar rats of SPF grade were randomly divided into 11 groups, namely blank control group, retention of coldphlegm in the lung model group and its treatment group （model A and treatment A）, retention of phlegm-heat in the lung model group and its treatment group （model B and treatment B）, deficiency of lung-Q/group and its treatment group （model C and treatment C）, deficiency of spleen-Q/ group and its treatment group （model D and treatment D）, and deficiency of kidney-Q/ group and its treatment group （model E and treatment E）, each containing 24 rats. The COPD model was induced by modified smoking and intratracheal instillation of lipopolysaccharide, and treated with corresponding interventions according to the grouping for the second modeling.②From the 30^th day, all the rats were drenched with pretreatment TCM mixture for 14 continuous days in various types of syndrome. Treatment A group： Xiaoqinglong decoction at the concentration of 0.6 g/mL, consisting of Ephedra, whir peony root and pinellia tuber at 9 g, cassia twig and licorice root at 6 g, zingiber, fructus schizandrae and Manchurian wildginger at 3 g; Treatment B group： Maxiong Shigan decoction at the concentration of 0.475 g/mL, consisting of 5 g Ephedra, 9 g almond, 6 g licorice root and 18 g gypsum; Treatment C group： Jade Screen Powder at the concentration of 0.15 g/mL, consisting of 3 g divaricate saposhnikovia root, 3 g milkvetch root and 6 g largehead atractylodes rhizome; Treatment D group： Liujunzi decoction at the concentration of 0.675 g/mL, consisting of ginseng, largehead atractylodes rhizome, Indian bread and dried tangerine peel at 9 g, prepared liquorice root at 6 g and pinellia tuber at 12 g; Treatment E group： ginseng and gecko combination at the concentration of 0.75 g/mL, consisting of apricot seed and liquorice root at 15 g, ginseng, Indian bread, fritillaria, white mulberry root-bark and common anemarrhena rhizome at 6 g, as well as 6 g gecko levigation. All the administrations were given 2 mL daily, which was 7.5 times as much as adults＇ dosage （Decoction tablet was offered by TCM Dispensary, Affiliated Hospital of Shangdong University of TCM）. In model group, the rats were injected intragastrically with 2 mL saline everyday, while the rats of blank control group were free to drink and eat without any intervention. ③The pathological changes of rat small airway were observed with light microscope, and electron microscope was used to observe the airway cilium of rats, which were analyzed with the evaluation and standard of small airway dysfunction. RESULTS： Totally 242 rats were involved in the result analysis, while others died in the experiment.①In blank control group, epithelial cells arranged orderly in mesobronchus and bronchium mucous membrane, pulmonary alveoli presented continuous structure and intact wall, without obvious exudation. In model groups, airway mucous hyperemia and edema appeared, epithelial cells were degenerated and erosive; Alveolar duct, alveolar sac and pulmonary alveolus were significantly enlarged, the spaces were thinner and broken, pulmonary alveoli was fused; The arterial blood vessel wall thickened, smooth muscle proliferated, lumens shortened and surrounding inflammatory cells infiltrated.②Compared with model groups, the treatment groups showed the cilium adhesion and lodging, the degeneration and necrosis of epithelial cell, as well as the inflammatory cell infiltration by light and electron microscopy. CONCLUSION： Classical prescriptions of TCM can relieve the inflammatory cell infiltration and secretion emphraxis in vessel cavity of bronchiole and terminal bronchiole of rats, and recover the cilium adhesion, lodging and abscission, improve the airway hyperreactivity and airway reconstruction, remiss the inflammation of COPD airway.
出处
《中国临床康复》
CSCD
北大核心
2006年第47期75-78,F0003,共5页
Chinese Journal of Clinical Rehabilitation
基金
山东省卫生系统高层次人才1020工程资助课题
山东省科技厅攻关计划资助课题(2002第17号)~~
作者简介
张伟 ，男，1963年生，山东省济南市人，汉族，1992年山东中医药大学毕业，硕士，主任医师，主要从事中医呼吸系统疾病的临床和科研方面的研究。
