| Chronic atrophic gastritis(CAG) is a common disease of digestive system. Its pathological changes was caused by inflammation, such as the destruction, reduce, shrink or even disappear of gastric glands, the loss of surface epithelial cell secretion capacity and mucosal thickening of the muscle. The last century 40's, Schindle first proposed the concept of CAG. WHO would be the CAG as a precancerous lesion of gastric cancer in 1978, CAG associated with intestinal metaplasia and dysplasia are precancerous lesions of gastric cancer. The possibility of cancer is larger. CAG and its precancerous lesions has become the focus of the study. Early detection, prevention and treatment of precancerous diseases and precancerous lesions, become a effective way of lower incidence and mortality of gastric cancer.The application of traditional Chinese medicine(TCM) in the treatment of chronic atrophic gastritis has a distinct advantage, the improvement of patient symptoms and to correct the effect of disease and so on, it is affirmative and significant.CAG disease would be attributed to "Epigastralgia, gaster-mass, consumptive disease" syndrome in TCM. Professor Diangui Li thinks that modern people's pressure of spirit and society become larger and disease patterns will changes with the development of society, lifestyle and diet changes. We observed many patients with chronic diseases that their conditions were repeated and refractory lingering in the clinical treatment.They had several clinical manifestations,such as dark cloud complexion, dark stagnation and less burnish, sticking and greasy stool, yellow urine, dark red body of the tongue, surname or greasy coated tongue, slippery pulse and so on. Professor Diangui Li introduced Zhuodu theory in the base of summarizing predecessor's theory combined with years of clinical experience .He think Zhuodu is one of pathopoiesis factors which can cause serious harm on the human entrails and meridian and the QI-blood of yin and yang. Meanwhile, it's the pathological products came from metabolic products which accumulated in the body when it's entrails functional disorders and QI-blood circulation is not normal.Three pathogenic characteristics of Zhuodu: (1)Zhuodu is hard to dissolve and easy inducing disorder of vital energy.(2) Zhuodu is easy entering blood and collaterals and inducing disorder of vital energy.(3) Zhuodu is easy inducing incoordination between vital energy and blood and forming blood stasis. The symptoms caused by Zhuodu belong to Zhuodu Zheng. It refers to a group or several groups of syndromes group which have specific clinical manifestations when the body is in the state of Zhuodu caused by Zhuodu.We have obtained a relatively satisfactory clinical efficacy applying Zhuodu theory in the treatment of CAG. The study aims at consummating further the symptoms law of the theory in CAG and exploring the mechanism of Huazhuojiedu prescription.At present, it is discordant that the viewpoint of many institute and medical scientist about the typing of CAG in TCM. Some Chinese medical scientist consider that the typing of CAG is GanWeiBuHe, PiWeiShiRe, ShiZhuoZhongZu, WeiLuoYuZu, PiWei XuRuo, WeiYingBuZu. But other Chinese medical scientist considered that the typing of CAG is GanWeiBuHe, PiWeiXuRuo, PiWeiShiRe, WeiYingBuZu, WeiLuoYuZu, PiXuQiZhi. At the same time, some Chinese medical scientist consider that the typing of CAG is QiYing LiangXu, XuHuoZuo Wei, PiWeiQiXu. The discrepancy about the typing of CAG in TCM increase difficulty in evolving clinical work and scientific research.The study about the symptom of TCM is the frontline of the research on TCM. Over 20 years, the investigative methods of quantizating applicated in studying on diagnostic criteria of Chinese medical symptom are increasing along with the permeating of the knowledge of statistics, epidemiology, metrology, vague mathematics and so on. Cluster analysis is one kind of multivariant statistical method whice can sort the sample or variables index to sample cluster analysis or variables cluster analysis according to theirs characteristics. Cluster analysis aims to classify those samples or variables index whice have similar character into one sort according to the similar degree among the samples or variables indexs. Reasonable application of cluster analysis in study on Chinese medical symptom can enormously raise specification and accuracy rating of differentiation of symptoms and signs in TCM.In this study, we have adopted the way of cluster analysis to analysis of large sample of cases of clinical manifestations and aim to provide reasonable scientific and normative differentiation of symptoms and signs for classification of syndrome for clinical, to investigate the regularity of symptoms and signs of Zhuodu Zheng.We tried to explore correlativity of the Zhuodu Zheng with the gut hormones by observing the change of the level of Gas, MTL and SS in patients of CAG and definite if the change of the level of gut hormones have variability in different type of syndrome of TCM, and if the abnormal content of gut hormones can lead different type of syndrome. The study can elevate our recognition about the Zhuodu Zheng of CAG.CAG is a kind of premalignant disease. CAG combining IM was known as atrophic typical indicate and gastric carcinomatous premonition. Through above-mentioned analysis, it was discovered that Zhuodu NeiYun was the principal characteristic of symptom of CAG, so we formulated HuaZhuoJieDu decoction and observed the curative effect of Huazhuo Jiedu decoction on treating CAG combining IM.At experimental point of view, we explored the possible mechanism of Huazhuo Jiedu to prevent and cure gastric carcinomatous precancerosis by observing the effect of Huazhuo Jiedu and their separate Huazhuo Jiedu decoction containing serum on proliferation and apoptosis of cultured human gastric cancer BGC-823 cell in vitro.Part 1: Study on Symptoms of Chronic atrophic gastritis in Traditional Chinese medicine by the way of Cluster analysis Objective:The study on the clinical data of CAG probed the regularity of different type of syndrome of TCM of CAG by the way of Cluster analysis. The study aims at exploring normative typing of syndrome of TCM of CAG and providing objective evidence for clinical differentiation of symptoms and signs by the way of modern mathematical statistics.Methods: The 371 patients visiting the clinic service or being in hospital at the Medical Department of Digestion of TCM Hospital of Hebei Province were diagnosed CAG according to the diagnostic criteria in modern medicine. Those patients are accordance with the criteria of internalizing and removing. The sysptoms,physical sign, tongues demonstration and pulse tracings of the 371 patients of with CAG were collected and recorded. We did Cluster analysis by SAS software for 56 variables through sorting 3-6 types.Results: The syndromes of these CAG Patients could be divided into 5 types: ZhuoDuNeiYun, GanWeiBuHe, WeiLuoYuZu, PiWeiXuRuo, WeiYing BuZu. The proportion explained was 72.74%. The principal and minor symptom of each type of syndromes of these CAG initially definited. The diagnostic criteria of ZhuoDuNeiYunZheng: the principal symptom and sign: chilly and cold limbs, stomachache, yellow thick and greasy fur,samll and smooth pulse; the minor symptom and sign: full sensation in the chest, distending pain over hypochondrium, halitosis, sunken pulse, even and soft pulse. The diagnostic criteria of GanWeiBuHeZheng: the principal symptom and sign: distention of stomach, eructation, wiry pulses; the minor symptom and sign: gastric upset, sour regurgitation, ill-temper, anorexia, eructation with foul odour and acidr regurgitation. The diagnostic criteria of WeiLuoYuZuZheng: the principal symptom and sign: prickle of stomach and tenderness, dimmish blackish complexion ,unsmooth pulses; the minor symptom and sign: nausea, tongue with ecchymosis, thin fur;The diagnostic criteria of PiWeiXu RuoZheng: the principal symptom and sign:felling of fulless and oppression, shortness of breath, loose stool, tongue with teeth marks on its margin; the minor symptom and sign:s,allow complexion, abdominal pain, acratia, pale tongue, weak pulse. The diagnostic criteria of WeiYing BuZuZheng: the principal symptom and sign: distending pain of stomach, tongue without fur, fissuared tongue, constipation, ripid pulses; the minor symptom and sign: dry mouth, sleepessness, slow pulse.Conclusions: The way of variable cluster analysis combined with the opinions of clinical expert could help us do reasonable syndrome differentiation for CAG patients. Meanwhile, ZhuoDuNeiYunZheng was inspected and verified rationally and scientifically as one new type of syndrome of CAG by the study. The study provides certain reasonable and scientific theoretical foundation for CAG on selection of treatment based on the differential diagnosis.Part 2: Study on dependablity of Zhuo Du Zheng of Chronic Atrophic Gastritis with Gut HormoneObjective: The study aims to reveal the characteristic of gut hormone secretion of the patient of CAG Zhuo Du Zheng and to provid objective evidence on indicatrix by investigating the dependablity of Zhuo du zheng with the changing of gut hormone.Methods: 50 patients who visited the Medical Department of Digestion of Traditional Chinese Medicine Hospital of Hebei Province between December, 2006 and December, 2007 were diagnosed CAG according to diagnostic criteria in modern medicine. Those patients who lived up to the criteria to internalize were divided into Zhuo Du group and Pi Xu group according to diagnostic criteria in Traditional Chinese Medicine. Healthy normal group also were composed of 25 healthy volunteers. The number of people in three groups all was 25.The level of gastrin, motilin and somatostatin in blood plasma were detected by radio-immunifaction.Results:1 The level of Gas in blood plasmaCompared with normal group, the level of gastrin in blood plasma of Zhuodu group didn't have marked change, there wasn't statistical significance between two groups(104.82±47.91 pg/ml VS 100.19±48.76 pg/ml, P>0.05).Compared with normal group, the level of gastrin in blood plasma of Pixu group remarkably decreased. There was statistical significance between two groups(79.17±34.02 pg/ml VS 100.19±48.76 pg/ml, P<0.05).Compared with Pi Xu group, the level of gastrin in blood plasma of Zhuodu group was higher. There was statistical significance between two groups(104.82±47.91pg/ml VS 79.17±34.02 pg/ml, P<0.05).2 The level of MTL in blood plasmaCompared with normal group, the level of motilin in blood plasma of Zhuodu group didn't have marked change, there wasn't statistical significance between two groups(302.89±126.82 pg/ml VS 326.00±58.76 pg/ml, P>0.05).Compared with normal group, the level of motilin in blood plasma of Pixu group remarkably decreased. There was statistical significance between two groups(208.72±85.21 pg/ml VS 326.00±58.76 pg/ml, P<0.05).Compared with Pixu group, the level of motilin in blood plasma of Zhuodu group was higher. There was statistical significance between two groups(302.89±126.82pg/ml VS 208.72±85.21 pg/ml, P<0.05).3 The level of SS in blood plasmaCompared with normal group, the level of somatostatin in blood plasma of Zhuodu group didn't have marked change, there wasn't statistical significance between two groups(11.81±6.34 pg/ml VS 10.10±7.20 pg/ml, P>0.05).Compared with normal group, the level of somatostatin in blood plasma of Pixu group didn't decreased. There wasn't statistical significance between two groups(10.95±6.87 pg/ml VS 10.10±7.20 pg/ml, P>0.05).Compared with Pixu group, There wasn't statistical significance between Zhuodu group and Pixu group(302.89±126.82pg/ml VS 208.72±85.21 pg/ml, P>0.05).Conclusions:1 The level of gastrin and motilin in blood plasma have variability in different type of syndrome of TCM of CAG .2 The change of the level of gastrin and motilin in blood plasma may be the reason to induce the different clinical manifestation among different type of syndrome.Part 3: Observated the clinical curative effect of chronic atrophic gastritis with intestinal metaplasia based on Zhuodu theoryObjective:This research aimed to observe clinical effect of treating chronic atrophic gastritis with intestinal metaplasia based on zhuodu doctrine.Methods: 92 patients of CAG with intestinal metaplasia were collected from the Medical Department of Digestion of TCM Hospital of Hebei Province. They were randomly divided into treatment group and control group.Treatment group were given Hua Zhuo Jie Du decoction twice a day and one pouch in once for treatment, but control group were given Wei Fu Chun three times a day and four pills in once for treatment. One course of treatment was 12 weeks,two course of treatment in all.Results:1 The compairson of clinical therapeutic effect between two groups:A total of 52 cases of treatment group, 17 cases of clinical recovery, 21 cases of clinical markedly, 11 cases of effective, 3 cases of invalid, the total effective rate was 94.23%. A total of 40 cases of control group, 7 cases of clinical recovery, 10 cases of clinical markedly, 8 cases of effective, 15 cases of invalid, the total effective rate was 62.5%. The difference of clinical curative effect between two groups was significant (P<0.01).2 The compairson of cardinal symptom score between two groups: After treating, the score of stomach pain, swelling of the liver is full, belching and debilitation decreased obviously in two groups.There was a significant difference bewteen before and after treating (treatment group and:1.32±0.51VS 4.82±1.25 P <0.01; control group:1.58±0.65 VS 4.69±1.17, P <0.01). After treatment, treatment group in the above-mentioned symptoms was significantly lower than the control group, there was a significant difference (1.32±0.51 VS 1.58±0.65, P<0.05).3 The compairson of gastroscopic effect between two groups: Gastroscopic curative effect of treatment group was superior to control group (The total effective rate in treatment group were 86.96%, 92%, 64.58%, 71.42%, 65.63%,the total effective rate control group were 60%, 78.95%, 38.23%, 36.36%, 31.82%, P<0.05 or P<0.01). Treatment group and control group comparisons to improve the mucosal oedema was no significant difference(The total effective rate in treatment group were 87.5%, the total effective rate control group were71.88%, P>0.05)4 The compairson of Gastic mucosa'pathological curative effect between two groups:The total effective rates of Treatment group in the improvement of gastric atrophy and IM, were 78.85%, 84.62%. The total effective rate control group were 52.5%, 55%. Gastic mucosa'pathological curative effect of treatment group was superior to control group(P<0.01).5 The compairson of the teradication rate of Hp between two groups: Two groups'curative effect of resising Hp infection were 47.22% and 44.44%. Two groups'curative effect of resisting Hp infection had no significant difference (P>0.05) .6 Detection of security indicators:There is no abnormal changes for Observation of blood, urine, conventional liver and kidney function and ECG changes before and after.Conclusions:1 Huazhuo Jiedu decoction can improve clinical symptoms in patients with CAG.2 Huazhuo Jiedu decoction can recover the gastric mucosa and improve intestinal metaplasia.3 Huazhuo Jiedu decoction can surely and partially resist Hp infection.Part 4:The effect on multiplication and apoptosis of human gastric cancer cell with drug-containing serum of Huazhuo Jiedu decoction and separate decoctionObjective: We observed the effect of multiplication and apoptosis to BGC-823 with drug-containing serum of Huazhuo Jiedu decoction and separate decoction in the experiment. The aim of it was to investigate if the Huazhuo Jiedu decoction could prevent precancerosis of CAG by the mechanism of action of inhibiting the cell to multiply and provide experimental evidence for clinical application.Methods:1 The preparation of drug-containing serum: 20 healthy male SD rats were randomly divided into four groups: normal group, Huazhuo Jiedu decoction group, Huazhuo decoction group, Jiedu decoction group.The amount of medicinal herb given to rats in Huazhuo Jiedu decoction group, Huazhuo decoction group, Jiedu decoction group was 345.9g·kg-1·d-1,208.4g·kg-1·d-1,137.3g·kg-1·d-1 weight respectively. Normal group were given 2ml isotonic Na chloride once a day by intragastric administration for 3 days. After anesthetizing by intraperitoneal injection hydral(350mg/kg), all rats were killed and draw blood by abdominal aorta. After standing, centrifugd for 10min, 3000rpm/min, deactivated by 56℃for 30min, finally, conserved in frigidaire -20℃for pre-emergency.2 Administration and subgroup: we treated BGC-823 cell with blank pastilleserum, Huazhuo Jiedu drug-containing serum, Huazhuo decoction drug-containing serum, jiedu drug-containing serum. We departed them into four groups, Huazhuo Jiedu decoction group, Huazhuo decoction group, Jiedu decoction group and control group.3 Detected the index: we deployed MTT, flow cytometry, cell immunohistochemistry to detect the growth inhibiting, cell cycle, apoptosis rate, the expression of Bcl-2 and Bax proteinum in BGC-823 cell with different drug-containing serum.Results:1 The experiment on inhibitation the multiplication of cell: Compared with control group, there was effect on inhibitation the multiplication of BGC-823 cell with Huazhuo Jiedu decoction, Huazhuo decoction and Jiedu decoction (P<0.05,P<0.01), especially, the effect of Huazhuo Jiedu decoction was evident, the rate of inhititation was 39.3%, 16.8%, 16.5% respectively. There was no different between Huazhuo decoction and Jiedu decoction in the effect of inhibitation.2 cell cycle: compared with normal group, great changes had happened in the cell cycle of BGC-823 with Huazhuo Jiedu decoction. The number of cell in G0/G1 stage increased (P<0.01), the number of cell in S stage decreased(P<0.01),there was no changes in G2/M stage, most of cells was hold in G0/G1 stage. But there was no changes in the cell cycle of BGC-823 with Huazhuo decoction and Jiedu decoction (P>0.05).3 Apotosis rate: the BGC-823 was treated with different Drug-containing serum, the bar chart of DNA emerged typical hypodiploid apoptotic peak.The result of FCM: the apotosis rate in Huazhuo Jiedu group prescription,Huazhuo decoction group and Jiedu decoction group was (16.85±0.63)%, (11.48±0.50)%, (12.38±0.60)% respectively.Compared with normal group (2.09±0.25)%, there was significant difference between them (P <0.01).There was significant difference between Huazhuo Jiedu decoction group, Huazhuo decoction group and Jiedu decoction group in apotosis rate (P <0.01). There was no difference, Huazhuo decoction group and Jiedu decoction group in apotosis rate (P>0.05).4 Detected the expression of Bcl-2 and Bax proteinum by cell immunohistochemistry: the masculine rate of expression Bcl-2 proteinum in huazhuojiedu group prescription, Huazhuo decoction group and Jiedu decoction group decreased greatly and they were (29.73±4.34)%, (37.11±4.63)%, (41.63±6.47)% respectively. Compared with normal group (53.74±2.97)%, there was significant statistical difference (P<0.01). There was significant difference between Huazhuo Jiedu decoction group,Huazhuo decoction group and Jiedu decoction group in the masculine rate of expression Bcl-2 proteinum (P<0.01). But there was no difference between Huazhuo decoction group and Jiedu decoction group (P>0.05). The masculine rate of expression Bax proteinum in huazhuojiedu group prescription, Huazhuo decoction group and Jiedu decoction group was (58.11±4.19)%, (32.25±2.93)%, (34.84±2.66)% respectively. Compared with normal group (25.17±2.36), there was significant difference (P<0.01). There was significant difference between Huazhuo Jiedu decoction group, Huazhuo decoction group and Jiedu decoction group in the masculine rate of expression Bax proteinum (P<0.01). But There was no difference between Huazhuo decoction group and Jiedu decoction group (P>0.05).5 Detected the expression of Bcl-2 and Bax proteinum with flow cytometry:Compared with normal group the expression of Bcl-2 in Huazhuo Jiedu group prescription,Huazhuo decoction group and Jiedu decoction group decreased (257.67±9.02 VS 330.22±7.13 P<0.01; 291.22±11.07 VS 330.22±7.13 P<0.01;276.20±9.10VS330.22±7.13 P<0.01).But the expression of Bax proteinum increased (330.14±8.19 VS 281.23±12.71 P<0.01; 303.84±6.60 VS 281.23±12.71P<0.05; 310.54±13.29 VS 281.23±12.71, P<0.01).There was significant difference between Huazhuo Jiedu decoction group, Huazhuo decoction group and Jiedu decoction group in the expression of Bcl-2 and Bax proteinum (P<0.01). There was no difference between Huazhuo decoction group and Jiedu decoction group in the expression of Bcl-2 and Bax proteinum(P>0.05).Conclusions:1 Huazhuo Jiedu decoction can inhibit BGC-823 cell multiplication, because it can interact cell cycle and induce apoptosis.2 Huazhuo Jiedu decoction, Hua Zhuo decoction and Jie Du decoction induce apoptosis may be according to increase the expression of Bcl-2 proteinum and decrease the expression of Bax proteinum in BGC-823 cell.3 Huazhuo decoction and Jiedu decoction can induce apoptosis, but it can not influence the cell cycle. The compatibility of Huazhuo Jiedu decoction can retard cell in G0/G1 stage, therefore it has remarkable effect on inhibiting the BGC-823 cell multiplication of gastric adenocarcinoma.Conclusions:1 Our study investigated the problem about the type of syndrome in TCM and indicated that Zhuodu Zheng is one common type of syndrome of CAG by the the way of cluster analysis.2 The level of gastrin and motilin in blood plasma have variability in different type of syndrome of traditional chinese medicine of CAG. The change of the level of gastrin and motilin in blood plasma may be the reason to induce the different clinical manifestation among different type of syndrome.3 Huazhuo Jiedu decoction can improve clinical symptoms and intestinal metaplasia , recove gastric mucosa in CAG patients.4 The drug-containing serum of Huazhuo Jiedu decoction and separate decoction can inhibit BGC-823 cell to multiply and enhance to apoptosis. It is possible the one of mechanism of this prescription prevented gastric cancer and reversed precancerosis.
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