摘要
一、文献研究
辨证论治是中医论治思想的精华所在,脾胃学说是中医理论体系的重要组成部分,脾胃湿热证是中医临床的常见证型之一。中医认为脾胃功能受损是脾胃湿热证发生的内在根本,而湿邪、热邪则为机体受外在侵袭后疾病形成的条件,内因、外因相互结合,共同促进湿热证的形成。其病性上属于实证,是以邪气盛为矛盾主要方面的一种病理反应,在临床上出现一系列脏腑功能失调的征候。而至现代,学者们借助各种先进的医学技术手段,从胃形态学、胃动力学、胃肠激素、炎症因子与保护因子、免疫化学、细胞内能量代谢及微生态等方面对脾胃湿热证作进一步的阐述,对其中西医理论本质进行全方位的深入探讨。
幽门螺杆菌(Hp)作为消化系统疾病最为重要的致病因素逐渐被人们所熟知。相关研究表明,在Hp感染相关胃病中,以脾胃湿热证占比例最多,肝胃不和、瘀血内阻等以实证为主要类型亦为重要。Hp相关性胃病尤其在炎症活动期,其临床、病理表现上亦被证明与脾胃湿热证致病特点相类似。另一方面,各种临床观察和药理研究表明,治疗脾胃湿热证的中药及方剂亦对Hp的根除有着明显的疗效。综上所述,脾胃湿热证与幽门螺杆菌(Hp)密切相关,部分学者提出Hp感染应属中医的“邪气”范畴,在致病性质上与湿热病邪是同等的。
幽门螺杆菌(Hp)经过近30年的研究发展,认为其致病机理可分为Hp在胃黏膜上的定植、Hp自身引起的胃黏膜损害、宿主免疫应答介导的胃黏膜损伤以及宿主因素等几大方面,但还仍有很多未知的领域需待进一步的探索。研究表明,Hp感染导致胃黏膜上皮和固有层大量浸润CD4+T细胞为主要类型的淋巴细胞。CD4+T细胞在功能上,代表着具有调控T淋巴细胞增殖与免疫能力的一类T细胞,故亦被称为辅助性T淋巴细胞(Th)。按照目前的主要分类,辅助性T淋巴细胞可分化为Th1和Th2两种类型。在生理条件下,机体Th1/Th2细胞的免疫功能处于动态平衡状态,一旦这种平衡发生偏离,机体就会趋向疾病状态。Th1细胞占优势时所介导的反应,表现在清除多种致病原,主要控制感染发展,倾向于引起严重的病理改变；Th2细胞占优势时主要反映的是抑制备病理产物或机体反应,造成疾病慢性发展的建立。
研究表明Th1/Th2细胞平衡与多种疾病密切相关,而对Th1/Th2细胞平衡与Hp相关胃病的关系一直是学者们的争论热点,在最后的研究中学者们倾向于Th1和Th2两种细胞的协同发挥对Hp相关胃病起到保护性免疫作用。在中医学上,学者们亦通过对中药、中药方剂的疗效进行研究,发现各种疾病、不同症状及不同的治疗手段所表现出Th1/Th2细胞平衡变化存在着差别,证明Th1/Th2细胞的动态平衡与中医辨证论治理论存在着一定的规律和相关性。
Th1/Th2细胞平衡学说与中医理论辨证论治的思想有着统一所在,无疑成为了阐述中医理论本质和指导临床治疗的新亮点,研究前景广阔无限。
二、临床实验研究
研究目的：通过检测人体外周血IFN-γ、IL-12、IL-4、IL-10的表达,从整体上分析Hp相关胃病脾胃湿热证与Thl/Th2平衡的相关性,并设立脾胃湿热证热重于湿组、湿热并重组、湿重于热组三个亚型以及脾气虚证组进行对照,探讨Hp相关胃病脾胃湿热证发生的病理机制,说明不同证型具有不同的发病机制,为进一步加强脾胃湿热证的现代研究,完善脾胃本质的探讨,以及提高中医药治疗脾胃病的临床疗效提供依据。
实验方法：
1、中医证型属脾胃湿热证和脾气虚证的胃病患者,其中脾胃湿热证52例(热重于湿9例,湿热并重21例,湿重于热22例),脾气虚证15例,并招募正常志愿者12名作为正常对照组。
2、各组受试对象均需于局部消毒后由专业护士抽取外周血4ml,进行人血清的制备。
3、采用安速Hp血清快速检测方法进行Hp感染判定。
4、采用液相蛋白芯片技术检测各组血清IFN-γ、IL-12、IL-4、IL-10的表达。
结果：
1、一般情况
各组的一般情况(性别、年龄、病程)差异未见统计学意义(P>0.05),各组间具有可比性。
2、Hp感染情况
脾胃湿热证组、脾气虚证组Hp感染率较正常组明显升高(P≤0.05),但脾胃湿热证组与脾气虚证组比较两者差别无统计学意义(P>0.05)。脾胃湿热证Hp阳性、Hp阴性两组间各主症积分均无明显差异(P>0.05)。
3、不同证型各组指标外周血的表达关系
IFN-γ、IL-12表达脾胃湿热证、脾气虚证组较正常对照组升高；IL-4表达脾胃湿热证、脾气虚证组较正常对照组降低；IL-10呈低水平表达,脾胃湿热证、脾气虚证组高于正常对照组；IFN-γ、IL-12、IL-4、IL-10脾胃湿热组表达均比脾气虚组升高。但以上结果比较差异均无统计学意义(P>0.05)。
4、脾胃湿热证组各亚型之间的比较
IFN-γ、IL-12、IL-4、IL-10表达均呈现为湿热并重组>热重于湿组>湿重于热组,但以上结果比较差异均无统计学意义(P>0.05)。脾胃湿热证组各亚型IFN-γ/IL-4、IL-12/IL-4的比较外周血浓度和荧光强度则呈现不同的趋势,外周血浓度IFN-γ/IL-4表现为湿热并重组>湿重于热组>热重于湿组,IL-12/IL-4表现为湿热并重组>热重于湿组>湿重于热组；而荧光强度IFN-γ/IL-4则表现为热重于湿组>湿热并重组>湿重于热组,IL-12/IL-4表现为湿热并重组>热重于湿组>湿重于热组。
5、Hp感染与Th1/Th2平衡的关系
脾胃湿热证组中Hp阳性和Hp阴性组比较,IFN-γ的表达Hp阳性组较Hp阴性组降低,IL-12的表达Hp阳性组较Hp阴性组升高,IL-4、IL-10的表达Hp阳性组较Hp阴性组降低。但以上结果比较差异均无统计学意义(P>0.05)。Hp感染与IFN-γ、IL-12、IL-4、IL-10表达均未见明显相关性。
结论：
1、脾胃湿热证胃病患者临床主要症状积分与Hp感染未见明显相关性。
2、脾胃湿热证的实证性质可能体现了Th1/Th2平衡中Th1免疫反应为主导的病理机制,Th1/Th2平衡也可能初步体现出人体正气强弱的情况。
3、脾胃湿热证患者湿热并重亚型可能较热重于湿、湿重于热亚型更加偏移于Th1/Th2平衡中Th1主导的免疫反应。
4、幽门螺杆菌(Hp)感染与Th1/Th2平衡未见明显相关性。
Treatment Based on Syndrome Differentiation is the foundation of Traditional Chinese Medicine (TCM).Splenogastric Hygropyrexia Syndrome is the common one of syndrome in the Splenogastric theory, which is one of important part of TCM. Splenogastric hygropyrexia syndrome originated as a result of the interaction of intrinsic and extirnsic factors, and it belongs to excess syndrome which is a pathological condition--both vital qi and evil qi are strong and struggle with each other. Nowadays splenogastric hygropyrexia syndrome becomes the focus of attention, some researchers made good use of advanced technology and explain every aspect clearly from gastric morphology, gastric motility, gastrointestinal hormones, inflammatory factors and protective factors, immunology, metabolism and microecology.
As the most important digestive disease risk factors, helicobacter pylori (Hp) are well known gradually. Research shows that splenogastric hygropyrexia syndrome account for a large proportion in H. pylori-associated gastropathy, and liver-stomach disharmony syndrome and blood stagnant syndrome as the main type of excess syndrome are also important. H. pylori-associated gastropathy particularly at its inflammatory active stage, it's proved that the clinical manifestations and pathological condition are similar to the pathogenic features of splenogastric hygropyrexia syndrome. On the other hand, a great deal of clinical observation and pharmacological studies have shown that some chinese traditional formula and patent medicine treated for splenogastric hygropyrexia syndrome also has a significant effect on the H. pylori eradication. In summary, there is a close relationship between splenogastric hygropyrexia syndrome and H. pylori. Some Chinese scholars take it for granted that H. pylori infection should be the "evil qi" category, H. pylori infection and "dampness and heat" pathogenic factors are equal.
After nearly 30 years of research and development, the pathogenetic mechanism of H. pylori can be divided into:colonization in the gastric mucosa, gastric mucosal damage induced by H. pylori, gastric mucosal damage mediated by the host immune response, host condition and some major factors, but there are still many unknown areas need to be further explored. The results show that, H. pylori infection lead to a large number of infiltrating CD4+ T cells as the main types of lymphocytes infiltrating into gastric epithelium and lamina propria. CD4+ T cells represent a kind of cells which have important function to regulate proliferation and immunity of T lymphocytes, so it can also be called as helper T lymphocytes (Th). According to some reseach at present, helper T cells differentiate into Thl and Th2 types. Under normal physiological conditions, the body's Thl and Th2 maintain in a state of equilibrium, and an imbalance of Thl/Th2 may increase the possibilities of suffering from disease. When Thl occupy a dominant position in the balance of Thl/Th2, the immune system eradicate different kinds of pathogens and control the development of major infection, but it tend to lead to severe pathological damage of human body; When Th2 occupy a dominant position in the balance of Thl/Th2, the pathological production and the function of immune system are inhibited, resulting in the establishment of chronic disease development.
Studies show that the balance of Thl/Th2 is closely related with many diseases, and there were some debates on the relationship between Thl/Th2 balance and H. pylori-associated gastropathy. Recently, some scholars tend to agree that the effect of protective immunity in H. pylori-associated gastropathy comes from the cooperation of thl and th2 cells. On the other hand, some scholars studied the efficacy of traditional Chinese medicine, and found that different stage of different disease and different treatment methods have shown the differences of Thl/Th2 balance, they think there may exist some regularity and relevant between Thl/Th2 balance and the theory of Traditional Chinese Medicine.
Objective:
The study is investigating the level of IFN-γ、IL-12、IL-4、IL-10 expression in peripheral blood, in order to analyse the relationship between splenogastric hygropyrexia syndrome in H. pylori-associated grastropathy and Th1/Th2 balance on the whole human body.And also contrast it with three types of splenogastric hygropyrexia syndrome(heavy dampness impairing heat, heavy heat impairing dampness, simultaneous onset of dampness and heat) and splenic deficiency syndrome group. To explore the pathomechanism of the H. pylori-associated gastrosia with splenogastric hygropyrexia syndrome, to illustrate that the different type of syndrome have different pathogenesis, in order to provide the basis for further strengthen the modern research of splenogastric hygropyrexia syndrome, improve the approach to the nature of spleen, and raise the clinical therapeutic effect of traditional Chinese medicine treatment of the spleen and stomach disease.
Method:
1. We chose 67 cases gastropathy patients including 52cases belonging to splenogastric hygropyrexia syndrome (among them,9 cases belong to the group of heavy heat impairing dampness, and 21 cases belong to the group of simultaneous onset of dampness and heat, and 22 cases belong to the group of heavy dampness impairing heat) and 15 cases splenic deficiency syndrome. And we recruited 12 healthy people as normal control group.
2. After disinfection, we got the blood of all objects by the nurse for the preparation of serum.
3. H.pylori was detected through ASSURE H. pylori rapid test.
4. We detected the expression of IFN-γ、IL-12、IL-4、IL-10 in serum through the liquid chip method.
Result:
1. Analysis of Common Materials.
The difference has no statistical significance on sex, age and the course of disease in every group(P>0.05). So we thought that all of the groups can compared each other.
2. Analysis of H. pylori Infection.
The rate of H.pylori infection of the group of splenogastric hygropyrexia and splenic deficiency syndrome are significantly higher than normal control group(P≤0.05), but the difference has no statistical significance between splenogastric hygropyrexia syndrome and splenic deficiency syndrome in groups. Besides, in the gastrogathy belonging to splenogastric hygropyrexia syndrome group, the difference has no statistical significance between Hp-positive and Hp-negative on the symptoms including yellow greasy tongue coating, stomach pain or gastric distention, anorexia and loose stool (P>0.05).
3. Relationship between the expressions of IFN-γ、IL-12、IL-4、IL-10 in peripheral blood of all groups.
The expressions of IFN-γ、IL-12 in splenogastric hygropyrexia syndrome group are higher than that in splenic deficiency syndrome group and normal control group; The expression of IL-4 is lower than that in splenic deficiency syndrome group and normal control group; The expression of IL-10 in all groups is in a low lever or does not exist. The expression of IFN-γ、IL-12、IL-4、IL-10 in splenogastric hygropyrexia syndrome group are all higher than that in splenic deficiency syndrome group. But all the datas have no statistical significance (P>0.05).
4. Relationship between the expressions of IFN-γ、IL-12、IL-4、IL-10 in the three types of splenogastric hygropyrexia syndrome group.
There is a tendency that the expressions of IFN-γ、IL-12、IL-4、IL-10 in the group of simultaneous onset of dampness and heat are higher than the group of heavy heat impairing dampness, which them are higher than the group of heavy dampness impairing heat, but all the datas have no statistical significance(P>0.05). Besides, there are not the same tendency between IFN-γ/IL-4 and IL-12/IL-4 in these three types of splenogastric hygropyrexia syndrome group.
5. Analysis of The Correlation between The Level of H. pylori and The Balance of Thl/Th2.
In the group of splenogastric hygropyrexia syndrome, the expression of IFN-γis lower in Hp-positive group than in Hp-negative group, the expression of IL-12 is higher in Hp-positive group than in Hp-negative group, the expressions of IL-4 and IL-10 are all lower in Hp-positive group than in Hp-negative group. But all the datas have no statistical significance(P> 0.05). There is no correlation between the level of H.pylori and The Balance of Thl/Th2.
Conclusion:
1. There is no significant correlation between H. pylori and the symptoms of gastropathy belonging to splenogastric hygropyrexia syndrome.
2. The texture of excess syndrome of splenogastric hygropyrexia syndrome probably reflects the pathological mechanisms when Thl occupy a dominant position in the balance of Thl/Th2, and the balance of Thl/Th2 can probably present the strong or weak condition of vital qi in human body.
3. There is a tendency that Thl in the balance of Thl/Th2 take more important role in the group of simultaneous onset of dampness and heat than the group of heavy heat impairing dampness and the group of heavy dampness impairing heat.
4. There is no correlation between the level of H. pylori and The Balance of Thl/Th2.
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