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滋肾通关解毒法干预前列腺特异性抗原(PSA)研究
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摘要
肿瘤是严重危害人类健康的疾病之一,肿瘤防治的关键在于早期发现、早期诊断,已成为人们的共识。目前肿瘤早期诊断主要依靠影像学、病理学等技术手段,一般在患者具有明显占位病变或出现临床症状后才得以确诊。然而从细胞癌变的生物学角度分析,占位病变已不是癌变早期,能够诊治难以发现的微小早期癌将对控制肿瘤发病率具有重要意义。肿瘤标记物的存在或量的改变可探索肿瘤的存在、性质、了解肿瘤的来源、细胞分化等,对肿瘤诊断、分类、判断预后及指导治疗具有一定意义。PSA等肿瘤标记物应用于肿瘤筛查,对肿瘤早期诊断、预后及治疗均具有重要价值。
     临床上相当一部分人群仅肿瘤标记物表达异常,但并未发现肿瘤病灶。如何有效干预肿瘤标记物异常表达,控制其向占位病变发展,是医学界值得探索的课题。中医辨证论治的个体化诊疗模式、整体调节的防治手段与治未病理念,对肿瘤标记物异常的治疗具有优势作用。本文以PSA异常但未发现前列腺癌病灶的特殊阶段为切入点,探讨滋肾通关解毒法干预PSA异常的作用与优势,全文分理论探讨、临床与实验机理研究三部分。
     理论探讨部分结合中医理论与临床实践,分析中医对肿瘤标记物异常的认识,阐述PSA异常病因、病机、病位、病性及病势变化,总结其辨治规律。提出脏腑功能失调,阴阳气血失衡,正气不足,毒邪留恋,郁滞气血津液是PSA异常表达的主要病因病机,尤以肾阴不足,膀胱气化不利为其主要病理特征,毒邪稽留为其主要致病因素。其病机复杂,本虚标实,虚实夹杂,病势变化多端,易滋生毒瘤,当早期干预,既病防变。PSA异常辨证论治宜宏观与微观结合、定正虚之部位、察邪正盛衰的程度,治以扶正祛邪之法,综合调节与PSA异常特征兼顾,及时治疗,防止肿瘤病灶形成,抑制其发展,提高生活质量。确立滋肾通关解毒法是治疗PSA异常的基本法则,“滋补肾阴、利尿化瘀、解毒抑瘤”是其立法特点。
     临床研究以滋肾通关解毒法为主要干预手段,对30例PSA异常、未发现前列腺癌病灶的患者进行疗效观察。结果显示该法对PSA异常恢复率达93%,临床症状有效率达98%。经治疗的病人无肿瘤发生案例,不仅解除了病人的忧虑,也未见任何副作用。
     实验研究以人雄激素依赖性前列腺癌LNCaP细胞分泌的PSA为研究对象,应用RT-PCR、western-blot及ELISA等技术检测本法干预后调控PSA表达的雄激素受体(AR)、抑癌基因P53等的变化情况,初步揭示本法下调PSA表达的分子机制。结果表明,该法通过降低AR、上调抑癌基因P53表达等机制实现抑制PSA表达作用。此外,该法对LNCaP细胞体外增殖有一定抑制作用,为“解毒抑瘤、既病防变”的立法思想提供了科学依据。
     研究证实:肾与膀胱功能失常,肾阴不足、膀胱气化不利,毒邪稽留,郁滞气血津液可导致PSA异常表达;肾阴不足,毒邪稽留与PSA异常表达及其疾病进展关系密切;滋肾通关解毒法是干预PSA异常的有效方法,该法源于临床,基于中医理论,疗效确切;滋肾通关解毒法立足“滋补肾阴、利尿化瘀、解毒抑瘤”,其抑制PSA表达的作用可通过降低AR、上调抑癌基因P53等机制,多层次、多角度、综合调节而实现。
Tumor is a serious disease hazard to human health. Early detection and diagnosis should be the key measure to tumor prevention and treatment. Currently, tumor generally diagnosed with obvious occupyinglesion or clinical symptoms,its early diagnosis mainly relies on imaging or pathology technologies. However, from the perspective of cancer biology, space occupying lesion may have not been the most early time of the cancer. So for the incidence of tumor control, it will be important to make a diagnosis and give treatment to the small early carcinoma.The existence of the tumor marker or its amount changes can explore the existence, nature, source or cell differentiation of the tumor, etc. According to this, we can classify, diagnose the tumor, and assess prognosis and guiding therapy for it. PSA and other tumor markers used in the cancer screening, they have an important value in early diagnosis, prognosis and treatment of tumor.
     From clinical practice, we find that quite a number of people only with tumor markers abnormal expression, but did not find the tumor lesions.The individualized diagnosis and treatment of Chinese medicine, concept of viewing the situation as a whole, overall adjustment means of prevention and control, and the early intervention which under the guidence of the concepts of preventive treatment have advantage to the treatment of this special phase.Through the early intervention effect by this treatment to the special period that PSA abnormal expression but without Prostate cancer lesions,this paper has discussed the early intervention effect and the advantages of the therapy that nourishing kidney yin,opening essence or water orifices and disintoxication to PSA abnormal expression,it is consisted by three parts that it is theoretical discussion, clinical efficacy observation and experimental study.
     Combinated the Chinese medicine theory and clinical practice,the part of the-oretical discussion has analysised the etiology, pathogenesis, pathogenic factors, disease location and potential changes of the special period for this disease, at the same time summarized its differential treatment. It proposed that dysfunctional organs, imbalance of yin and yang, the lack of healthy Qi,the pathogenic toxin stagnation of the qi, blood or fluid is the main etiology and pathogenesis of PSA abnormal expression, especially kidney yin deficiency, bladder gasification negative and pathogenic toxin accumulation can cause the disease.Its pathogenesis is complex, such as origin deficiency and excess in superficiality, mixture of deficiency and excess, and disease tendency changes fast are the charectersfor the disease, and it easily become a malignant tumor, so early intervention is necessary. The syndrome differentiation and treatment for PSA abnormal should put the macroscopic and microcosmic syndrome differentiation in combination, observate the position of body resistance deficiency, inspect the tide of healthy energy or pathogenic factors then treat by the supporting healthy energy to eliminate pathogenic factors method. Meanwhile, considering the anomaly characteristics of the PSA, timely treatment to prevent the tumor lesion formation, inhibit tumor's development, and improve the quality of life. And then we establish the fundamental early intervention therapy that nourishing kidney yin,opening essence or water orifices and disintoxication method, and the basic characteristic of the method is "nourishing kidney yin, diuresis or dissolving blood stasis, detoxification to inhibit tumor growth".
     By the method as the main means, the clinical analysis section discussed the clinical curative effect after the method intervention in30patients, whose PSA abnormal but without prostate cancer. Results show that this treatment method has quick effect, and obviously improved symptoms.The PSA abnormal complete remission rate was93%, and the clinical symptoms effective rate was98%. During the treatment, there was no deterioration record and drugs cause side effects.
     Experiment study discussed the mechanism for the method to inhibite the PSA abnormal expression. Using RT-PCR, western-blot and ELISA techniques, puting the PSA which secreted by the human androgen dependent LNCaP cell as the research object, we have tested the changes of androgen receptor (AR) and the tumor suppressor gene P53which control the expression of PSA to reveal the possible molecular mechanism for this method decreased PSA expression.Experiment results show that, the therapy can be through different mechanisms to decrease PSA expression, such as reducingthe AR, up-regulation tumor suppressor gene P53or apoptosis gene Bax expression and so on.Moreover, this method has certain inhibitory effect on the proliferation of LNCaP cells in vitro, this can offers some experimental foundation for the legislation idea "detoxification to inhibition of tumor generation "of the treatment method.
     Through the above researches we get the following conclusion:kidney and bladder dysfunction, kidney yin deficiency and bladder gasification was bad, the pathogenictoxin stagnation of the qi, blood and fluid can cause PSA abnormal expression; Pathological changes of kidney yin deficiency and pathogenic toxin factors accumulation is closely related to this disease; the therapy of nourishing kidney yin,opening essence or water orifices and disintoxication which derived from clinical, based on the theory of Chinese medicine, and its curative effect is exact its an effective method for the early intervention of PSA abnormal expression; this method based on the legislation idea "nourishing kidney yin, diuresis ordissolving blood stasis, detoxification to inhibite tumor generation "has its theoretical, clinical and experimental basis; this therapy may from multi-angle, multi-level or comprehensive adjustment, through the possible mechanisms such as lowering the AR, increaseing tumor suppressor gene P53to realize the inhibitory effect for PSA abnormal expression.
引文
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