马玉琛教授风湿性间质性肺病痰毒并治研究
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摘要
导师马玉琛教授认为风湿性间质性肺病应属于《素问·痹论》肺痹,与一般具有咳、哮、痰、喘症状的慢性支气管炎、肺气肿、肺炎等不同：一是伴有五体痹,有不同程度的肢体症状；二是肺脏症状缠绵反复,重浊粘滞。结合其雍膨肿胀的临床表现,符合广义有形之痰,为顽痰、积痰、痰核之类；或疼痛剧烈,或关节畸形,肌肉萎缩,这种浸淫腐蚀、损害严重等特点,也符合邪实蕴结体内,久而酿生之内毒。其在现代辅助检查的微观表现,如CT的肺纤维化、条索样变,病理的肺泡结构紊乱、扩张、陷萎,泡腔渗出瘀积,泡壁增厚、断裂,肺泡间隔纤维化,胶原纤维增生,以及系列免疫指标的改变,也符合传统中医痰和毒的特点,可以认为是痰、毒侵袭或内生,痰积毒淫,痰结蕴毒,毒存助痰,坏血食气,蚀筋腐肉过程的表现。提出痰毒共同致痹,风湿性间质性肺病与痰、毒关系尤为密切,以及无毒不足以治痹,药物毒性相对论,痹病痰毒并治等观点。本课题秉承先生以上观点,应用痰毒并治法,并以先生经验方雄附散为主,对风湿性间质性肺病进行了动物实验研究和前瞻性临床对照研究。
诊断明确的本院住院风湿病患者,参考美国胸科协会和欧洲呼吸学会标准,选择其中间质性肺病63例纳入观察,常规中药辨证治疗,治疗组33例加雄附散(雄黄,僵蚕、白附子)冲服,治疗3个月；疗效评定：治疗组显效6例,有效21例,与对照组有效率对比X2=6.70,P<0.05；肺病症状,肺功能,CT影像变化：治疗后各项指标及与对照组比较都有显著性意义(P<0.05)。实验观察雄附散干预博莱霉素诱导的肺间质纤维化大鼠模型,肺组织中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性明显高于其它各组(P<0.01),丙二醛(MDA)含量明显低于各药物干预组(P<0.01)。提示雄附散能够干预痰积毒蚀的过程可能与其早期提高受损组织中抗氧化酶活性,从而有效阻断氧自由基引发肺组织纤维化过程。对其机制还应进一步研究。
Professor Ma Yu-chen thinks that rheumatosis-related interstitial lung disease can be considered as Arthromyodynia in lung from TCM theory. It is different from the common lung disease, such as chronic bronchitis, pulmonary emphysema and pneumonitis, which are characterized by cough, wheeze, phlegm and gasping. It has two individual features. Firstly, patients feel uncomfortable in limbs, which are called Arthromyodynia in five-ti. Patients may have arthralgia, joint deformities or muscle atrophy. Those destructions of joints coincide with the damage caused by "Toxin". Secondly, the lung symptoms persist for a long time and are easy to recur. These can be distinguished as phlegm syndromes. Besides, both CT manifestation and histopathology observation show the typical appearance of pulmonary fibrosis. The microscopic observation and the changes of its related immune indexes are in accordance with "Phlegm" and "Toxin" theories. In conclusion, rheumatosis-related interstitial lung disease can be considered as the consequence of invasion and turbid accumulation of "Toxin" and "Phlegm". So Professor Ma argues that a combination of expelling toxin and eliminating phlegm can be effective in the treatment of rheumatosis-related interstitial lung disease. This study was aimed to testify this view and to evaluate the efficacy of Xiongfusan on the treatment of rheumatosis-related interstitial lung disease by animal trial and clinical trial.
In the clinical trial, a total of 63 patients diagnosed with rheumatosis-related interstitial lung disease from Department of rheumatology in our hospital were randomly assigned into two groups. There are 30 patients in control group treated with regular decoction, and 33 patients in treatment group treated with Xiongfusan. Three months was a treatment course. As a result, there was significant difference on effective rate (x2=6.7 P<0.05). There are significant differences between two groups in the symptoms, the lung function and CT manifestation. In the animal trial, we found that enzymatic activity of SOD and GSH-PX were obviously higher than other groups (P<0.01) and the level of MDA was lower (P<0.05) in the lung tissues of the herbal treatment group. These showed that Xiongfusan can promote the activity of antioxidant enzyme in the damaged tissue, stop the fibrosis process initiated by oxygen free radical. Its concrete mechanisms should be studied in the future.
诊断明确的本院住院风湿病患者,参考美国胸科协会和欧洲呼吸学会标准,选择其中间质性肺病63例纳入观察,常规中药辨证治疗,治疗组33例加雄附散(雄黄,僵蚕、白附子)冲服,治疗3个月；疗效评定：治疗组显效6例,有效21例,与对照组有效率对比X2=6.70,P<0.05；肺病症状,肺功能,CT影像变化：治疗后各项指标及与对照组比较都有显著性意义(P<0.05)。实验观察雄附散干预博莱霉素诱导的肺间质纤维化大鼠模型,肺组织中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性明显高于其它各组(P<0.01),丙二醛(MDA)含量明显低于各药物干预组(P<0.01)。提示雄附散能够干预痰积毒蚀的过程可能与其早期提高受损组织中抗氧化酶活性,从而有效阻断氧自由基引发肺组织纤维化过程。对其机制还应进一步研究。
Professor Ma Yu-chen thinks that rheumatosis-related interstitial lung disease can be considered as Arthromyodynia in lung from TCM theory. It is different from the common lung disease, such as chronic bronchitis, pulmonary emphysema and pneumonitis, which are characterized by cough, wheeze, phlegm and gasping. It has two individual features. Firstly, patients feel uncomfortable in limbs, which are called Arthromyodynia in five-ti. Patients may have arthralgia, joint deformities or muscle atrophy. Those destructions of joints coincide with the damage caused by "Toxin". Secondly, the lung symptoms persist for a long time and are easy to recur. These can be distinguished as phlegm syndromes. Besides, both CT manifestation and histopathology observation show the typical appearance of pulmonary fibrosis. The microscopic observation and the changes of its related immune indexes are in accordance with "Phlegm" and "Toxin" theories. In conclusion, rheumatosis-related interstitial lung disease can be considered as the consequence of invasion and turbid accumulation of "Toxin" and "Phlegm". So Professor Ma argues that a combination of expelling toxin and eliminating phlegm can be effective in the treatment of rheumatosis-related interstitial lung disease. This study was aimed to testify this view and to evaluate the efficacy of Xiongfusan on the treatment of rheumatosis-related interstitial lung disease by animal trial and clinical trial.
In the clinical trial, a total of 63 patients diagnosed with rheumatosis-related interstitial lung disease from Department of rheumatology in our hospital were randomly assigned into two groups. There are 30 patients in control group treated with regular decoction, and 33 patients in treatment group treated with Xiongfusan. Three months was a treatment course. As a result, there was significant difference on effective rate (x2=6.7 P<0.05). There are significant differences between two groups in the symptoms, the lung function and CT manifestation. In the animal trial, we found that enzymatic activity of SOD and GSH-PX were obviously higher than other groups (P<0.01) and the level of MDA was lower (P<0.05) in the lung tissues of the herbal treatment group. These showed that Xiongfusan can promote the activity of antioxidant enzyme in the damaged tissue, stop the fibrosis process initiated by oxygen free radical. Its concrete mechanisms should be studied in the future.
引文
1 童学彪.五脏痹实质探讨[J].南京中医药大学学报,1996,12(6)：6-7.
2 宋建平.肺纤维化的中医药治疗研究近况[J].中医药信息研究杂志,1998,5(6)：13-14,22.
3 宋建平.肺痹古今论[J].中华医史杂志,1998,28(4)：212-215.
4 范永升主编.金匮要略.长沙：湖南科学技术出版社,2000：43-44.
5 冯兴华.《素问·痹论》与现代风湿病学[J].中医杂志,2008,49(5)380-381.
6 姚楚芳,林意菁,蒋树龙.浅谈肺痹与肺间质纤维化[J].中西医结合学报,2004,2(4)：295-296.
7 董振华.从《内经》五脏痹理论探讨风湿病多系统损害的治疗[J].北京中医,2006,(25)6：347-350.
8 钟丽丹,洪鸿彬.陈湘君教授治疗风湿病肺间质病变经验介绍[J].新中医,2006,38(10)：13-15.
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10 周贤梅,戴令娟,侯杰.风湿病肺间质病变的临床特点[J].医师进修杂志,2002.25[10]：17.
11 赵红英,李晓明,王健等.原发性干燥综合征肺间质病变临床分析[J].实用心脑肺血管病杂志,2008,16(6)：49-50.
12 刘涛,宋良文.肺纤维化发生的分子机制和早期防治研究进展[J].军事医学科学院院刊,2003,27：312-316.
13 高惠英,李小峰.结缔组织病所致间质性肺疾病的研究进展[J].国际呼吸杂志,2007,27(9)：673-675.
14 王勇,马玉琛.痰毒并治类风湿性关节炎致肺间质纤维化[J].中国中医急症,2009,18(3)：395-402.
1 周贤梅,戴令娟,侯杰.风湿病肺间质病变的临床特点[J].医师进修杂志,2002,10(25)10：15-17.
2 周继朴,苑惠清.益气活血化痰解毒中药静点与口服联用治疗特发性肺间质纤 维化急性期的临床研究[J].中华中医药学刊,2008,26(9)：2074-2076.
3 袁成波.小青龙汤加味治疗间质性肺疾病(ILD)—(寒饮伏肺,肺络痹阻证)的临床研究[D].中国优秀硕士学位论文全文数据库,2009,(02)
4 胡蕙蕙,闻胜兰.6例急性间质性肺炎临床分析[J].全科医学临床与教育,2008,6(4)：347.
5 陈亚红,姚婉贞,杨薇等.糖皮质激素治疗特发性间质性肺炎31例临床分析[J].北京大学学报(医学版),2002,12：722-725
6 杨永滨,王勇,马玉琛,等.雄附散抑制大鼠肺间质纤维化过程中肺组织iNOS的表达水平[J].医学研究与教育,2009,26(6)：1-3.
7 王勇,杨永滨,马玉琛.雄附散对抗博莱霉素诱导的大鼠肺间质纤维化的作用机制[J].军医进修学院学报,2010,31(1)：513-515.
8 马玉琛,杨永滨,王勇,等.雄附散阻抗大肺间质纤维化的病理形态观察[J].武警医学,2010,21(2)：131-134.
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1 童学彪.五脏痹实质探讨[J].南京中医药大学学报,1996,12(6)：6-7.
2 宋建平.肺纤维化的中医药治疗研究近况[J].中医药信息研究杂志,1998,5(6)：13-14,22.
3 宋建平.肺痹古今论[J].中华医史杂志,1998,28(4)：212-215.
4 范永升主编.金匮要略.长沙：湖南科学技术出版社,2000：43-44.
5 姚楚芳,林意菁,蒋树龙.浅谈肺痹与肺间质纤维化[J].中西医结合学报,2004,2(4)：295-296.
6 钟丽丹,洪鸿彬.陈湘君教授治疗风湿病肺间质病变经验介绍[J].新中医,2006,38(10)：13-15.
7 王勇,马玉琛.痰毒并治类风湿性关节炎致肺间质纤维化[J].中国中医急症,2009,18(3)：395-402.
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9 王勇,杨永滨,马玉琛.雄附散对抗博莱霉素诱导的大鼠肺间质纤维化的作用机制[J].军医进修学院学报,2010,31(1)：513-515
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14 马玉琛,杨永滨,王勇等.雄附散阻抗大肺间质纤维化的病理形态观察[J].武警医学,2010,21(2)：131-134.
15 杨永滨,王勇,马玉琛等.雄附散抑制大鼠肺间质纤维化过程中肺组织iNOS
的表达水平[J].医学研究与教育,2009,26(6)：1-3.
2 宋建平.肺纤维化的中医药治疗研究近况[J].中医药信息研究杂志,1998,5(6)：13-14,22.
3 宋建平.肺痹古今论[J].中华医史杂志,1998,28(4)：212-215.
4 范永升主编.金匮要略.长沙：湖南科学技术出版社,2000：43-44.
5 冯兴华.《素问·痹论》与现代风湿病学[J].中医杂志,2008,49(5)380-381.
6 姚楚芳,林意菁,蒋树龙.浅谈肺痹与肺间质纤维化[J].中西医结合学报,2004,2(4)：295-296.
7 董振华.从《内经》五脏痹理论探讨风湿病多系统损害的治疗[J].北京中医,2006,(25)6：347-350.
8 钟丽丹,洪鸿彬.陈湘君教授治疗风湿病肺间质病变经验介绍[J].新中医,2006,38(10)：13-15.
9 赵建宏.中西医结合治疗系统性红斑狼疮肺间质病变28例[J].山东中医杂志,2003,22(9)：549-550.
10 周贤梅,戴令娟,侯杰.风湿病肺间质病变的临床特点[J].医师进修杂志,2002.25[10]：17.
11 赵红英,李晓明,王健等.原发性干燥综合征肺间质病变临床分析[J].实用心脑肺血管病杂志,2008,16(6)：49-50.
12 刘涛,宋良文.肺纤维化发生的分子机制和早期防治研究进展[J].军事医学科学院院刊,2003,27：312-316.
13 高惠英,李小峰.结缔组织病所致间质性肺疾病的研究进展[J].国际呼吸杂志,2007,27(9)：673-675.
14 王勇,马玉琛.痰毒并治类风湿性关节炎致肺间质纤维化[J].中国中医急症,2009,18(3)：395-402.
1 周贤梅,戴令娟,侯杰.风湿病肺间质病变的临床特点[J].医师进修杂志,2002,10(25)10：15-17.
2 周继朴,苑惠清.益气活血化痰解毒中药静点与口服联用治疗特发性肺间质纤 维化急性期的临床研究[J].中华中医药学刊,2008,26(9)：2074-2076.
3 袁成波.小青龙汤加味治疗间质性肺疾病(ILD)—(寒饮伏肺,肺络痹阻证)的临床研究[D].中国优秀硕士学位论文全文数据库,2009,(02)
4 胡蕙蕙,闻胜兰.6例急性间质性肺炎临床分析[J].全科医学临床与教育,2008,6(4)：347.
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