【作者】 陶波；

【导师】 李云英；

【作者基本信息】 广州中医药大学 ， 中医五官科学， 2006， 博士

【摘要】 喉癌前病变(Laryngeal Precancerosis)乃喉上皮增生性病变(epithelial hyperplastic lesions of the larynx,EHLL)中的一种特殊类型,是一类比正常粘膜更易发生癌变的病理学变化。主要包括有慢性肥厚性喉炎(hyperplastic laryngitis);喉角化症(keratosis of the larynx),包括喉黏膜白斑病(leukoplakia)和喉厚皮病(pachydermia);成人的喉乳头状瘤(papilloma of the larynx)。临床上并非所有的喉癌前病变都最终发展为喉癌,一些可部分或完全消退,部分保持原有形态,仅少数在内源性和外源性有害因素作用下继续恶化或演变成癌。因此,及早识别和控制这些病变,研究其临床表现、病理组织学特点及其与恶变之间关系,对防止癌变的发生发展在理论上和实践上都有重要意义。 中医古籍中并无“喉癌前病变”这一名称,但根据其反复不愈的声嘶特点,把其归属于“慢喉喑”“喉瘤”的范畴。喉癌前病变的喉局部表现为粘膜充血暗红肥厚、增生隆起,与中医学的血瘀证相一致,微循环障碍为其最基本的病理改变。中医证候本质是反映人体生理、病理的改变,应与蛋白质的变化有密切关系,蛋白质的动态性、可调节性、可加工、可修饰性更符合中医证候的可变性、多样性,因此,研究蛋白质与中医证候的相关性有重要意义。 本课题以与喉癌前病变密切相关的诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和血管内皮生长因子(vascular endothelial growth factor,VEGF)为切入点,采用免疫组织化学技术,从细胞、分子水平上探讨喉癌前病变与中医血瘀证密切相关的微观指标,以及微循环障碍在癌前病变到发生癌变这一量变到质变的过程中所起的影响,找寻一种有助于判断喉癌前病变发展趋势的量化微观指标,确定其基本中医证型,同时观察具有活血化瘀散结作用的金喉片对本病的干预作用,应用中医药阻断和逆转喉癌前病变,为中医药进行防癌、抗癌治疗提供理论和临床依据。 一、文献研究 本文先推本溯源,复习了中医学古文献中有关喉癌前病变病名、病因、病机及治疗等方面文献,并且对近十年来关于中医治疗喉癌前病变研究进展作了一综述。然后概述了西医学对喉癌前病变的概念、病因、分类、诊断及治疗,诱导型一氧化氮合酶和血管内皮生长因子与喉癌的关系以及嗓音的客观检测等相关研究进展。 二、临床研究 目的:探索金喉片对血瘀型喉癌前病变的干预作用。 方法:选取符合纳入标准的血瘀型喉癌前病变患者30例,采用金喉片口服治疗,每次4片,每日3次,以14天为一疗程,连续用药2个疗程,在治疗第14天、第28更多还原

【Abstract】 Laryngeal precancerosis is a particular type of EHLL. It is a kind of pathologic change which is more inclined to be cancerated than the normal mucous membrane. It mainly includes hyperplastic laryngitis, keratosis of the larynx (including leukoplakia and pachydermia) and adults’ papilloma of the larynx. In clinic, not all the precancerosis of laryngeal cancer finally lead to laryngeal cancer. Some of them can partly or even completely disappear. Some of them remain its precancerous condition. Only minority of them will deteriorate into laryngeal cancers owing to endogenous or exogenous harmful factors. So, it plays a significant role in preventing the cancerization of laryngeal cancers both in theory and practice by diagnosing and controlling the pathological changes betimes, studying it’s clinical manifestation, histological features and the relationship between their histological features and canceration.Laryngeal precancreosis was never mentioned in TCM ancient books. However, it was classified into the chronic hoarseness in light of its characteristic of repeated hoarseness. The local symptom in patient’ s throat manifests itself as congestive, purple mucous membrane with hypertrophy hyperplasia and swelling, which is consistent with the blood stasis TCM theory. Circulation disorder is the basic pathological changes of the disease. The essence of TCM symptom reflects the physiologic and pathologic changes in human body which was considered to have close relationship with protein changes. Furthermore,the instability and adjustability of protein are more consistent with thevariability and variety of symptom in TCM. So, the study on the correlation between protein and TCM symptom is significant.INOS and VEGF were taken as the breakthrough point, which all have close relation with laryngeal precancerosis, with the immunohistoche-mical technique, We tried to find some micro-indexes that can indicate the correlation between laryngeal precancerosis and the blood stasis syndrome in TCM from cellar and molecular level, studying how micro-circulation disorder effects human body in the process from a precancerous condition to cancer, looking for some objective microindexes which are helpful to estimate the developing trend of Laryngeal precancerosis, identifying what type of syndrome a certain case is, observing the effects of the JinHou tablet which has been proved to be able to activate blood and dissipate stagnation as well. It can provide a lot of evidences of preventing and treating cancers with Chinese medicine by the research of blocking and reversing laryngeal precancerosis with Chinese medicine.1 Literature studyAt the beginning we made a review about the names, causes, pathomechanism and treatments of laryngeal precancreosis in ancient books. We also gave a general summarization about the recent progress in treating laryngeal precancerosis with Chinese medicine in recent 10 years. Then the research progress of the definition, causes, classification, diagnosis and therapy of Laryngeal precancerosis in western medicine theory, the relationship study on between the carcinoma of larynx and the INOS and the VEGF, the voice objective detection as well were all summarized.2 Clinical studyObjective:To investigate the efficacy of intervention of the JinHou tablet on the treatment of laryngeal precancerosis with blood stasis syndrome.Methods:30 cases with proved laryngeal precancerosis identified as blood stasis syndrome were chosen. The patients in the trial group were treated with JinHou tablets per os, with a dose of four tablets every time, three times a day. A course consists of 14 days. All the treatment lasted for two courses. A symptom and physical sign examination and computing analysis of voice were conducted respectively at the 14th, 28th day and two months later. The safety were checked once pre-treatment and post-treatment respectively. Self PA comparision statistical method were implemented to the analysis of thecurative effects.Results:A course later, the dominant healing rate was 43.30%. 83.30% for the end of the treatment, 73. 30% for the two -month - later-follow-up survey. There was significant difference between pre-treatment and post-treatment in the symptoms, physical signs and parameters of voice (includes SHIMMER JITTER NNE MPT) (P< 0. 01). No reverse effects was observed among 20 patients in the trial group. The safety of all cases is grade one.Conclusions:The JinHou tablet has the function of activating blood circulation, removing blood stagnation and dissipating stasis. The clinical study proved that the JinHou tablet can remarkably improved laryngeal precancerosis patient’ s symptoms, physical signs as well as the voice quality. So, the tablet has a definite effect to treat laryngeal precancerosis by blocking up the development of canceration of laryngeal precancerosis without any harmful or side effect. Therefore, it deserves to be popularized and used in clinicin treating such disease. 3 Laboratory study Objective:To investigate the correlation between the essence of TCM syndrome of laryngeal precancerosis and the expression of INOS and VEGF in the level of genetic protein expression.Methods:10 paraffin embedded samples of laryngeal precancerosis identified as blood stasis syndrome were chosen as the trial group and 10 paraffin embedded tissue sections of laryngeal precancerosis with phlegm-dampness syndromes were chosen as the control grouop. 10 paraffin-embedded materials of laryngeal cancer stored in the department of pathology in Guangdong provincial TCM hospital were chosen as the laryngeal cancer grouop. Respectively, measuring their expression of INOS/VEGF and protein with the immunohistochemical technique.Results:? In the laryngeal cancer group, the positive expression rate of the JNOS and VEGF is 100.00% and 90.00% respectively. While in the trial groui/\he/~~rate is 80. 00% and 60. 00% respectively. In the control group, the rate is 30. 00% and 30. 00% respectively. There was siginificant difference between any two groups in the positive rate of the INOS and VEGF among three groups.(2) There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy (P<0. 01) .(3) There was a positive correlation between the expression of the INOS and the expression of the VEGF (/>< 0. 05) .Conclusions:(D The experimental study showed that VEGF and iNOS of all samples in three groups expressed positively at different degrees. There was a significant difference in the expression of IONS and VEGF between any two groups among three groups. There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy. Base on the results mentioned above, we considered that blood stasis syndrome in TCM is the basic TCM type of laryngeal precancerosis.(2) There was a positive correlation between the expression of INOS and VEGF. So, we considered that in the process of blood vessel generating of laryngeal precancerosis or laryngeal cancer, INOS and VEGF may interact to accelerate the generation of new blood vessel, which play an important role in the onset and development of laryngeal cancer. 4 ConclusionsThe JinHou tablet has a definite effect to treat laryngeal precancerosis. It can remarkably improve the patient’ s voice quality, blocking up the development of canceration of laryngeal precancerosis. The expression of INOS and VEFG can be an index for evaluating the disease condition of laryngeal precancerous and forecasting the risk of canceration. The blood stasis syndrome is a basic TCM type of laryngeal precancerosis.更多还原