节点文献
肺纤方治疗肺间质纤维化的临床与实验研究
【作者】 张晓梅；
【导师】 姜良铎；
【作者基本信息】 北京中医药大学 ， 中医内科学， 2006， 博士
【摘要】 本研究探讨了肺纤方治疗肺间质纤维化的理论依据、临床疗效及其对博来霉素肺间质纤维化大鼠的影响。在文献回顾和导师经验总结的基础上进行了理论研究,认为反复外感、环境毒邪、肺肾亏虚是肺间质纤维化的发病原因。瘀血痰浊为肺间质纤维化基本病理产物,痰瘀深伏凝滞、肺络痹阻为肺纤维化致病关键;反复外感加重肺纤维化进展,瘀浊痹阻肺络加重气虚、易致阴虚。肺间质纤维化分为慢性进展期和急性加重期。肺间质纤维化治则治法为:慢性进展期治以补肺益肾化痰活血通络,急性加重期兼以清热养阴。姜良铎教授在长期临床实践中针对病机总结出肺纤方治疗肺间质纤维化取得较好疗效。临床研究开展了肺纤方治疗肺间质纤维化的系统临床观察。根据西医诊断标准筛选病例,共收集病例40例发病一年内的中期早期患者,分为肺纤方组和强的松组对照,中药组给予肺纤方治疗,激素组给予强的松0.5-0.25mg/kg体重,观察治疗效果,并监测不良反应。同时检测病人血清中基质金属蛋白酶1、2组织金属蛋白酶抑制剂TIMP1、2的水平,以评价中药对于肺间质纤维化患者基质的影响。结果显示:中药肺纤方在临床疗效、在改善症状、提高生理指标(肺功能、动脉血氧分压)方面明显优于强的松。肺纤方在治疗期间的肺再感染次数明显低于激素组。肺纤方能明显降低血清中基质金属蛋白酶2、13、基质金属蛋白酶抑制剂TIMP1、2的水平。肺纤方治疗特发性肺间质纤维化患者的疗效,可能与肺纤方对肺间质纤维化基质重建的调节,而发挥其抑制肺纤维化的作用。试验研究开展了肺纤方与强的松组、模型组和空白对照组的试验研究。Wister大鼠87只,随机分为空白对照组15只,经气管插管注入生理盐水1ml/kg;模型组、肺纤方组与强的松组各24只,经气管插管注入博来霉素1mg/kg造模;造模后第二天开始灌胃。分别于造模后第14天、28天、45天处理动物,空白组每个时间点各5只,模型组、肺纤方组与强的松组每个时间点各8只。右肺进行肺病理检测,行HE染色比较肺泡炎程度,Masson染色比较肺纤维化程度。左肺制成肺匀浆液检测层粘连蛋白、Ⅰ型、Ⅲ型胶原、基质金属蛋白酶9、13,左肺制成肺匀浆液检测氧化损伤产物谷胱甘肽和丙二醛。大鼠血清检测基质金属蛋白酶1、2及组织金属蛋白酶抑制剂1、2。研究结果显示肺纤方组和强的松组较模型组对肺间质纤维化大鼠模型均有明显的抑制作用。肺纤方组较强的松组更能有效改善大鼠纤维化的程度,抑制层粘连蛋白、氧化物丙二醛、谷胱甘肽、Ⅰ型、Ⅲ型胶原、基质金属蛋白酶9、13、大鼠血清检测基质金属蛋白酶1、2及组织金属蛋白酶抑制剂1、2的产生,在肺间质纤维化大鼠45天时尤其明显,说明肺纤方有显著抑制肺间质纤维化大鼠基质重建的作用和较强的抗氧化损伤作用。既往中医药治疗肺间质纤维化的临床与实验研究着重探讨了中药对肺间
【Abstract】 The theoretical basis, clinical effects of Feixian Fang(FXF) treating idiopathic pulmonary fibrosis and its effects on rats with pulmonary fibrosis induced by bleomycin(BLM) have been explored in this paper.The theoretical study has been carried out on the basis of literature review and the summary of advisor’s experience. It is considered that the etiological factors of pulmonary fibrosis are repeated suffering of exogenous pathogen, environmental pathogen, deficiency of lung and kidney. The basic pathological products of pulmonary fibrosis are blood stasis and phlegm turbid, the key point of pathopoiesis are that phlegm and stasis hide deeply and stagnated, the pulmonary collaterals are blocked. Repeated suffering of exogenous pathogen accelerates the development of pulmonary fibrosis, pulmonary collaterals blocked by stasis and turbid aggravates qi deficiency, which results in yin deficiency easily. Pulmonary fibrosis is divided into chronic progression stage and acute exacerbation stage. The therapeutical principle and methods of pulmonary are as follows: invigorating lung and kidney, eliminating phlegm and promoting blood circulation to remove meridian obstruction in chronic progression stage, clearing heat and nourishing yin in acute exacerbation stage. After long-term clinical practice, professor Jiang Liangduo composed FXF aiming at pathogenesis and satisfactory effects have been achieved.The clinical study included systematical clinical observation of FXF treating pulmonary fibrosis. According to modern medicine diagnostic criteria, the cases had been sifted. 40 case of middle stage and early stage patients with invasion within one year had been collected, who were divided into FXF group and control group with prednisone, the Chinese medicine group rats were administrated with FXF, while the hormone group rats were administrated with prednisone, 0.5-1mg/kg body weight. The therapeutic efficacy was observed and the adverse effects were monitored. Meanwhile, the levels of matrix met alloproteinase 1,2, tissue inhibtor of met alloproteinase (TIMP1,2) were tested, so as to evaluate the effects of Chinese medicine on ground substance of patient with idiopathic pulmonary fibrosis. The results indicated that the Chinese medicine FXF was better than prednisone in aspects of clinical effects, improving symptoms, enhancing physiogical index(pulmonary function, arterial partial pressure of oxygen). The pulmonary reinfection frequency during the treatment period of FXF was lower than that of prednisone, the FXF could lower the levels of matrix met alloproteinase(MMP1,2,) and tissue inhibtor of met alloproteinase (TIMP1,2), which indicated that FXF probably exhibited its inhibiting pulmonary fibrosis effect through rebuilding pulmonary ground