【作者】 郭海；

【导师】 龚婕宁；

【作者基本信息】 南京中医药大学 ， 中医临床基础， 2010， 博士

【摘要】 老年肺炎是老年人呼吸系统常见病、多发病,其发病率和病死率往往随年龄增高而增高,病情随年龄增长而加重。鉴于本病人群的特殊性和病情的复杂性,加之现代社会老年人群的逐渐增多,老年肺炎已经成为临床呼吸系统最为常见的疾病之一。在西医治疗效果不理想的情况下,采用中西医结合的方法就显得尤为重要。根据本病的临床特征,应属温病肺热证的范畴。为了寻求临床更好的中医治疗方法,本研究在中医温病学理论指导下,对宣肺清气法的临床运用进行了理论、临床和相关的实验研究。本研究主要分为四部分,第一部分为文献综述,主要对国内外中医和西医治疗老年肺炎的研究成果进行综述。现代医学在未获得病原体和药敏结果前,主要根据院内外细菌感染的规律,经验型选用具有强力杀菌作用的抗生素控制感染,多主张联合用药。多数学者认为,虽然临床有抗生素和多种支持疗法的综合治疗,但由于老年肺炎患病率高、病情进展快、临床症状多不典型、漏诊率高、并发症多、临床症状缓解慢、涉及病种较多,加之老年人体质特殊和基础疾病多等特点,治疗效果仍不能令人满意。认为老年肺炎的发生主要有两个方面,一为正气不足,一为温邪袭肺；初期和中期的临床表现多以痰、热、咳、喘、气急等气分症状为主,多以邪热壅肺、肺气郁闭为病机,治疗应主要针对肺热,同时也要兼顾肺闭,既要清解气分邪热,也要宣肺开闭。中医药治疗老年肺炎具有一定优势,宣肺清气法在清解肺热的同时兼顾宣肺开闭,在临床应用上获得了明显的效果,所以有必要对宣肺清气法治疗老年肺炎的机理进行深入研究。第二部分主要对老年肺炎的有关理论进行研究,认为虚、痰、郁、瘀交织是老年肺炎的体质特征,并且贯穿于病程的始终。肺热炽盛、体虚邪实是老年肺炎的病机特点；热邪伤正,肺络闭阻是老年肺炎发生变证的主要原因,可出现心阳暴脱、邪陷心包、化源欲绝、肺脏痿弱等险恶证候。由于本病肺热炽盛、郁闭于内是病情发展的重要原因,因而提出：宣肺清气法是治疗老年肺炎的重要方法。宣肺清气法是指在清解气分邪热中有机的配合轻清宣畅肺气的药物,使肺经邪热宣泄而出的治疗方法。该法既能宣畅肺气使邪热透达外解,又能清泄肺热避免邪热内郁生变,在本病早、中期邪在气分时使用可以取得良好疗效。运用宣肺清气法治疗老年肺炎的基本原则是明确主症、把握病程,其中以肺热炽盛为辨证要点,以病程初、中期为常用阶段。同时,立足主法、灵活变化也是正确应用该法的关键,要考虑到老年患者的特殊体质和病程中的兼夹因素,随证加减或适当配合其它治疗方法,如化痰止咳、降气平喘、活血化瘀、益气养阴、润燥通下、清营凉血等,方能尽快控制肺部炎症,促进机体康复。第三部分为临床研究,选择江苏省中医院呼吸科60例老年社区获得性肺炎住院病人,按照随机、对照原则,分为治疗组和对照组各30例。对照组给予西医常规治疗(包括一般治疗、对症治疗和抗生素治疗),治疗组在对照组治疗的基础上同时给予中药宣肺清气方。试验结果：(1)疾病疗效比较：在治愈率、显效率和有效率的具体数值上,治疗组均高于对照组,但两组各率的比较在统计学上均无显著性差异,疗效相当。(2)证候疗效比较显示,治疗组明显优于对照组。两组显效率比较,具有明显差异,治疗组明显优于对照组。(3)单项症状体征比较：治疗组在缓解发热、恶寒、咳嗽、咳痰和舌质方面未见明显的优势,但对于退热时间、脉象和肺部啰音的改善情况,治疗组有着明显的优势。(4)两组血清WBC、N、CRP水平在治疗后均有显著下降,但两组治疗后的差值比较无统计学意义；对照组治疗前后ESR无显著差异,但治疗组治疗前后ESR有显著差异,两组治疗前后的差值比较亦有显著差异,治疗组明显优于对照组。试验结果表明,宣肺清气方在缓解症状、改善体征、缩短退热时间和改善肺部啰音等方面具有一定优势。第四部分为实验研究。为了进一步研究宣肺清气法的作用机理和预防由肺炎引发的肺纤维化的作用,进行了以下实验研究：(1)宣肺清气方对博莱霉素致大鼠肺损伤和死亡保护率的影响。结果发现,该方能降低肺损伤的程度,抑制肺指数的升高,在肺损伤早期具有明显的死亡保护作用。表明宣肺清气方具有宣肺祛邪,抑制炎症反应和保护肺脏的作用。(2)宣肺清气方对肺损伤大鼠免疫功能的影响,实验观察到该方能够降低博莱霉素诱发肺损伤大鼠TNF-α、IFN-γ、IL-4的水平。表明该方的作用机制之一,可能是通过影响炎症因子及抗感染免疫相关因子,达到治疗急性肺损伤和防止肺纤维化的目的。(3)宣肺清气方对博莱霉素致大鼠肺纤维化的干预作用。研究表明,宣肺清气方能够降低博莱霉素诱发大鼠肺泡炎和肺间质纤维化程度。(4)宣肺清气方对肺纤维化大鼠ERK1/2和NF-κB信号通路的影响。结果提示,该方能明显降低模型大鼠肺组织ERK1／2和NF-κB水平,与模型组有显著差异。表明宣肺清气方预防和治疗肺纤维化的作用机制之一,可能与干预ERK1／2和NF-κB等信号通路的激活有关。总之,论文从文献、理论、临床、实验四个方面研究了宣肺清气法治疗老年肺炎的有关问题,初步阐明了该法的作用机理。其研究结果,不仅可为临床治疗老年肺炎提供中医理论指导,也为今后进一步的理论研究和临床、实验研究奠定了良好基础。更多还原

【Abstract】 Pneumonia in elderly, a common and frequently-occurring respiratory disease, has increasing morbidity, mortality and severity with aging. Because of specificity of the affected population, complexity of the disease and the growth of the aged population, pneumonia in elderly is one of the most common respiratory diseases.Combined treatment of Chinese medicine with modern medicine is salient while modern medicine has dissatisfactory treatment.According to clinical characteristics, this disease could be put under the category of febrile diseases. For the sake of better TCM treatment, under the guidance of the theory of febrile diseases, clinical application of Declaring Lung and Eliminating Qi is discussed from the aspects of theory research, clinical observation and experiments.The research is divided into 4 parts. The first part, literature reviews, mainly reviews the achievements of domestic and overseas research on treatment of pneumonia in elderly by Chinese medicine and modern medicine. Western medicine chooses potent antibiotics and comprehensive treatments according to bacterial infection rule in hospitals and in communities, before the results of pathogens and susceptibility test come out. Most scholars suggest that all the above treatments can not generate effects because of the high rate of infections, fast progress, atypical clinical symptoms, high rate of missed diagnosis, many complications, slow clinical remission, many related diseases, specificity of the aged and their basic diseases. The reasons of occurrence of pneumonia in elderly include weak resistibility and febrile evils invading lung. The initial stage and intermediate stage are manifested with sputum, heat, cough, wheezing and dyspnea. The pathogenesis is accumulation of pathogenic heat in the lung and failure of lung qi in dispersion. Treatment of Declaring Lung and Eliminating Qi focuses on relieving lung-heat and dispersion failure. TCM has advantages in treatment of pneumonia in elderly. Therefore, study of the mechanism of such law should be furthered.The second part mainly studies TCM theories of pneumonia in elderly. Intertwining of deficiency, phlegm, depression and stagnation is the constitutional characteristic of pneumonia in elderly. Exuberant lung-heat, physically weakness and evil pathogens are its pathogenesis. Heat evils damaging vital qi and closure of lung collaterals are the main reasons of deteriorated cases, causing sudden depletion of heart yang, invasion of cardial sac by pathogen, breathing failure and lung atrophy. So, the law of Declaring Lung and Eliminating Qi is an important treatment of pneumonia in elderly. The law refers to combination of drugs of ventilating lung qi when clearing heat at qi, to dispel lung heat and avoid the stagnation of evil heat. There is an obvious effect at the initial stage and intermediate stage. The basic application principle of Declaring Lung and Eliminating Qi is identifying main syndromes and grasping disease courses. Exuberant lung-heat is a key symptom differentiation. At the same time, the special physic constitution and other factors should be taken into account. Other treatment methods, such as eliminating sputum and reliving cough, lowing qi to dispel asthma, promoting blood circulation to remove blood stasis, nourishing qi and yin, moistening dryness and catharsis, and cooling yingfen and blood, should be combined to control lung infection as soon as possible to promote recovery.In partⅢ,clinical research,60 cases of conformed senile CAP from Chinese Medicine Hospital of Jiangsu Province were randomly divided into a control group (30 cases), treated with general treatment and anti-infective therapy, and a treatment group (30 cases), treated with Ventilating-lung-qi and clearing-heat Formula, general treatment and anti-infective therapy.Results:(1) There is no statistically significant difference between two groups in cure rate, marked effect and effective power, that is to say, the efficacy of two groups are equivalent.(2) The comparison of syndrome’s effect shows that the effect of the treatment group was significantly better than that of the control group. Comparing the two groups markedly effective, there was with significant differences and significantly better than the control group. (3) Comparison of individual symptoms and signs:There is no obvious advantage in the treatment group in dealing with fever, aversion to cold, cough, sputum, and tongue. But there are advantages in fever time, pulse, and pulmonary rales.(4) The levels of serum WBC, N, CRP were significantly decreased after treatment, but the difference between the two groups was no of statistical significance. ESR level in the control group has no significant difference before and after treatment, but that of the treatment group has significant difference. The difference in the two groups before and after treatment is also significant The treatment group was significantly better than the control group. The results of clinical trial show that Ventilating-lung-qi and clearing-heat Formula has some advantages in relieving symptoms and signs, reducing fever time and improving pulmonary rales.In part IV, experiments, to further study mechanism of the law of Declaring Lung and Eliminating Qi and prevention of pulmonary fibrosis caused by lung infections, the following experimental studies were carried out:(1) experiment of protecting acute lung injury and protection impact on death rates induced by bleomycin treated by Ventilating-lung-qi and clearing-heat Formula:the prescription can reduce the degree of acute lung injury, inhibit increase of lung index and has a significant protective effect in the early lung injury. The result shows that the prescription has the role of ventilating lung qi and eliminating evils, inhibiting inflammatory response and protecting lung. (2) experiment of the prescription in affecting immunity of acute lung injury in rats induced by bleomycin:the prescription can reduce the degrees of TNF-a, IFN-y, IL-4 levels of bleomycin-induced lung injury in rats. It shows that one mechanism of the prescription to treat acute lung injury and to prevent pulmonary fibrosis could be affecting inflammatory factors and anti-infection immune-related factors. (3) experiment of the prescription in interfering Bleomycin-induced pulmonary fibrosis in rats:the prescription can reduce the degree of bleomycin-induced pneumonia and pulmonary fibrosis.(4) experiment of the prescription in affecting ERK1/2 and NF-KB signal pathway of pulmonary fibrosis in rats:the results suggest that the prescription can significantly reduce the levels of ERK1/2 and NF-KB of lung tissues and has significantly difference compared with the model group. It shows that this is one of mechanisms of the prescription in treating acute lung injury and preventing pulmonary fibrosis via interfering with ERKl/2 and NF-KB signal pathway.In short, four parts above initially illustrate the mechanism. Its findings not only provide TCM theoretical guidance for clinical treatment of pneumonia in elderly, but also lay a good basis for further theoretical, clinical and experimental studies.更多还原