基于浊毒学说应用化浊解毒方治疗慢性萎缩性胃炎癌前期病变的临床疗效观察及机制探讨
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摘要
浊毒学说是近年来提出的一个重要学说，其源于临床实践，在实践中检验发展。慢性萎缩性胃炎癌前期病变为临床常见病、多发病，但逆转萎缩、肠化尚待进一步研究证实。于是我们在治疗时有意识运用化浊解毒药物，总结确立了“浊毒”学说，并指导临床辨证论治用药。然而各类文献记载中对浊毒的散在描述，缺乏系统的总结，为了提高对该学说的认识，在第一部分将浊毒的定义、浊毒的发展历程、浊毒的病因病机、浊毒的致病特点、浊毒证的临床表现、浊毒证治则、浊毒证的常用方剂、浊毒证常用中药进行系统论述。在第二部分回顾性分析以化浊解毒方为主治疗的238例慢性萎缩性胃炎癌前期病变的患者的病历，总结其临床疗效及浊毒证的主要症状及舌脉；确定化浊解毒为主的治疗大法，并根据个体差异辨症（证）治疗的临床辨证方法。在第三部分观察化浊解毒方治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴证患者的临床疗效，并观测患者胃蛋白酶原、血流变的改变，以期为慢性萎缩性胃炎癌前期病变浊毒内蕴提供物质基础并探讨其机制。在第四部分观察化浊解毒方治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴患者的临床疗效，并观测患者胃液成分的改变及对胃泌素的影响，并进一步探讨其机制。第一部分浊毒学说的形成及理论体系
目的：以历史文献记载及临床经验为依据探讨浊毒学说渊源及理法方药，进而提出新的学术观点及理论体系。
方法：梳理历代医家中对浊毒的记载，以探讨其源流，如实采集和原始保存名老中医药专家的诊疗经验，建立名老中医药专家独特诊疗信息数据库，形成浊毒学说的理法方药。
结果：梳理出浊毒的源流，探讨了浊毒的浊毒的历史沿革、病因病机致病特点、临床症候、治则治法、常用方剂、常用中药，从临床论证了浊毒学说的实用性。
结论：浊毒学说具有完善的理法方药体系，可用于指导临床实践。
第二部分238例慢性萎缩性胃炎伴癌前期病变患者应用化浊解毒方治疗2年回顾性分析
目的：探讨慢性萎缩性胃炎癌前期病变患者浊毒证的主要表现、舌脉，并以化浊解毒为主，结合个体差异，辨（症）证治疗的辨证方法。
方法：对238例经胃镜及病理诊断为CAG伴癌前期病变的门诊患者进行回顾性分析，并对癌前病变发生逆转的36例患者其治疗前后胃镜及病理进行比较。
结果：
1研究发现慢性萎缩性胃炎患者女性偏多，年龄以中老年为多，具有肿瘤家族史者比例偏低。慢性萎缩性胃炎癌前期病变患者，舌质暗、苔腻、脉弦细滑为浊毒证最常见舌脉，这也符合临床经验，十大症状在浊毒内蕴的基础上存在其个体差异，可根据十症（证）辨证治疗。
2在238例慢性萎缩性胃炎患者中，临床总有效率为79.0%，胃镜改变总有效率为77.7%，病理改变总有效率为74.4%。
3内镜下类型变化
癌前病变逆转的36例患者，随访前黏膜红白相间，以白为主12例，皱壁变平甚至消失，黏膜血管显露3例，黏膜呈颗粒或结节状17例，糜烂17例。
癌前病变逆转的36例患者，随访后黏膜红白相间，以白为主10例，皱壁变平甚至消失，黏膜血管显露5例，黏膜呈颗粒或结节状10例，糜烂12例。
4病理改变
癌前病变逆转的36例患者，随访前中度异增6例、轻度异增8例、重度肠化7例、中度肠化5例、轻度肠化11例、灶性肠化5例。
癌前病变逆转的36例患者，随访后中度异增0例、轻度异增1例、重度肠化0例、中度肠化0例、轻度肠化10例、灶性肠化1例。
5癌变的转归情况：癌前期病变经过化浊解毒治疗没有发生腺癌的病例。
结论：慢性萎缩性胃炎癌前期病变，病理均具有肠上皮化生和（或）不典型增生（上皮内瘤变）的改变。病理微观辨证及舌暗苔腻，脉弦细滑可以作为慢性萎缩性胃炎癌前期病变浊毒证诊断依据，在慢性萎缩性胃炎癌前期病变患者中并根据个体差异，可以出现十大主要症状，以化浊解毒治疗为大法对慢性萎缩性胃炎癌前期病变患者进行治疗，根据主要症状，辨（症）证治疗，既突出化浊解毒的特色，又不失辨证论治的原则。
第三部分化浊解毒方治疗慢性萎缩性胃炎癌前期病变115例临床观察及对PG、血流变的影响
目的：观察化浊解毒方治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴证患者的临床疗效及对PG、血流变的影响，并进一步探讨其机制。
方法：
治疗组：给予化浊解毒方(处方：白花蛇舌草15g、半枝莲15g、茵陈15g、黄连15g、藿香15g、全蝎9g、蜈蚣4g等),每日1剂。分早晚2次空腹服。
对照组：给予胃复春片，每次４片，每天３次，饭前30min服用。
两组在治疗时停用其他治疗慢性胃炎的药物。两组均以３个月为１个疗程，共治疗２个疗程。
结果：
1两组临床综合疗效比较
治疗组总有效率为86.7%，对照组总有效率为67.2%，两组患者总有效率比较差异有统计学意义(p<0.01)。
2两组内镜、病理疗效比较
内镜治疗组与对照组比较，经统计学处理，差异有显著性。治疗组总有效率为85.0%，对照组为56.4%，治疗组疗效明显为优(p<0.05)。病理治疗组与对照组比较，经统计学处理，差异有显著性。治疗组总有效率为83.3%，对照组为65.5%，治疗组疗效明显为优(p<0.05)。
3胃蛋白酶原表达情况比较
两组患者胃蛋白酶原治疗后胃蛋白酶原Ⅰ升高、胃蛋白酶原Ⅱ降低。治疗组治疗前胃蛋白酶原Ⅰ108.32±17.27mPa s，治疗后143.17±17.81mPa s；胃蛋白酶原Ⅱ治疗前10.74±1.88mPa s，治疗后7.48±1.69mPa s，差异有统计学意义(p<0.05)。对照组治疗前胃蛋白酶原Ⅰ104.92±15.17mPa s，治疗后胃蛋白酶原Ⅰ123.66±16.91mPa s；对照组治疗前胃蛋白酶原Ⅱ10.93±1.78mPa s，治疗后8.42±1.62mPa s，差异有统计学意义(p <0.05)。治疗后，治疗组胃蛋白酶原Ⅰ升高明显高于对照组，差异有统计学意义(p <0.05)，治疗组胃蛋白酶原Ⅱ降低明显高于对照组，差异有统计学意义(p <0.05)。
4两组患者治疗前后血液流变学指标比较
两组治疗前后全血粘度比较，差异均有统计学意义（p<0.05）。治疗组治疗前全血粘度高切值5.95±0.89mPa s，治疗后3.74±0.37mPa s，治疗组治疗前全血粘度低切值5.95±0.89mPa s，治疗后15.35±1.11mPa s；对照组治疗前全血粘度高切值5.66±0.72mPa s，治疗后全血粘度高切值4.08±0.36mPa s，对照组治疗前全血粘度低切值20.29±1.87mPa s，治疗后16.02±1.38mPa s。治疗后治疗组全血粘度高切值改善优于对照组，差异具有统计学意义（p<0.05）,全血粘度低切值改变不明显，差异无统计学意义（p>0.05）
结论：1化浊解毒方能减轻患者胃黏膜充血、水肿、糜烂，缓解黏膜白相、颗粒增生等胃镜征象，提高患者癌前期病变病理的治愈率。
2慢性萎缩性胃炎伴肠化、不典型增生（上皮内瘤变）时，因其分泌PGⅡ，可导致血清中PGⅡ上升，对胃黏膜产生破坏，血粘稠度常增高、血流缓慢不利于萎缩的黏膜的修复。
3化浊解毒方可能通过降低胃蛋白酶Ⅱ的表达及降低血粘稠度，改变胃黏膜环境状态，进而阻止癌前期病变的进一步发展，甚至逆转。第四部分化浊解毒方对慢性萎缩性胃炎胃癌前病变患者胃液成分及
GAS的影响
目的：观察化浊解毒法治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴证患者的胃液成分及GAS的影响。
方法：
治疗组：给予化浊解毒方(处方：白花蛇舌草15g、半枝莲15g、茵陈15g、黄连15g、藿香15g、全蝎9g、蜈蚣4g等)，每日1剂。分早晚2次空腹服。
对照组：给予胃复春片，每次４片，每天３次，饭前30min服用。
两组在治疗时停用其他治疗慢性胃炎的药物。两组均以３个月为１个疗程，共治疗２个疗程。
结果：
1两组临床综合疗效比较
治疗组总有效率为80.0%，对照组总有效率为62.1%，两组患者总有效率比较差异有统计学意义(p <0.01)。
2两组内镜及病理疗效比较
治疗组与对照组比较，经统计学处理，差异有显著性。内镜治疗组总有效率为81.7%，对照组为75.9%，治疗组疗效明显为优(p <0.05)。病理治疗组总有效率为75.0%，对照组为62.1%，治疗组疗效明显为优(p<0.05)。
3两组胃液成分比较
对两组患者胃液中游离酸、总酸、乳酸及亚硝酸盐进行治疗前后的比较。治疗前，两组胃液中游离酸、总酸、乳酸及亚硝酸盐含量比较，差异无统计学意义（p>0.05）。治疗后，两组患者胃液中游离酸及总酸含量均较治疗前有所提高，与对照组比较，治疗组增加更为明显(p<0.05)；乳酸和亚硝酸盐含量较治疗前明显降低(p<0.05)，与对照组比较，治疗组乳酸下降更为明显，差异有统计学意义(p<0.05)。
4两组患者胃泌素水平治疗前后的比较
治疗前，两组胃泌素水平比较，差异无统计学意义（p>0.05）。治疗后，两组患者胃泌素水平均较治疗前有所降低，与对照组比较，治疗组降低更为明显(p<0.05)。
结论：1化浊解毒方能减轻患者胃黏膜充血、水肿、糜烂，缓解黏膜白相、颗粒增生等胃镜征象，提高患者癌前期病变病理的治愈率。
2慢性萎缩性胃炎癌前期病变患者总酸及游离酸含量降低，亚硝酸盐及乳酸升高，亚硝酸盐为常见的致癌物质，可能促进癌前期病变的进一步发展。胃泌素反应性升高，可能促进肠化或不典型增生（上皮内瘤变）的黏膜细胞的分裂增殖。
3化浊解毒方可能通过降低胃泌素表达，改善患者胃液成分，增加总酸及游离酸含量，降低乳酸及亚硝酸盐含量，促进胃黏膜的修复，阻止胃癌前病变进一步发展。
The zhuodu doctrine is an important doctrine proposed in recent years, tomake a contribution to the enrichment and development of traditional Chinesemedicine. The zhuodu doctrine derived from clinical practice, applied toclinical, should be tested and improved for real application. Precancerouslesion of chronic atrophic gastritis is the clinical common diseasefrequently-occurring disease. But the reverse atrophic and intestinalmetaplasia is yet to be further study, so it prompt us to expand way of thinking,research and development a new theory and method. And apply the drugs ofhuazhuojiedu to the therapy consciously, so the theory of zhuodu wereestablished, and clinical medication by syndrome differentiation. The theoryfor the treatment of chronic atrophic gastritis pre-cancerous lesions opens up anew train of thought. However, in all kinds of literature about the zhuoduscattered on the description of the zhuodu is all a lack of detailedunderstanding. In order to increase awareness of the doctrine, in the first part，the definition of zhuodu, development process of zhuodu, pathogene sis ofzhuodu, virulence characteristics of zhuodu, syndrome clinical manifestationsof zhuodu, treatment principles of zhuodu, common formula of zhuodu,Chinese medicine commonly used of zhuodu are Systematically discussed. Inthe second part, it is a retrospective analysis of medical records about the mainhuazhuo jiedu formula that treatment238cases of chronic atrophic gastritis inpatients with precancerous lesions, summarize the clinical efficacy and themain symptoms and tongue and pulse, establish the primary way of huazhuojiedu treatment, and according to individual differences determine the clinicalsyndrome treatment methods. In the third part, we observe the clinical efficacyof huazhuo jiedu formula on the precancerosis of chronic atrophic gastritis with the syndrome of accumulation of turbidity and toxicity, and observationof patients pepsinogen change, changes in hemorheology to chronic atrophicgastritis of precancerous lesions, to provide the material basis foraccumulation of turbidity and toxicity and its mechanism. In the fourth part,we observe the clinical efficacy of huazhuo jiedu formula on the precancerosisof chronic atrophic gastritis with the syndrome of accumulation of turbidityand toxicity, and observation the impact on the stomach secrete hormone whenpatients gastric juice change, and further explore its mechanism.
PartⅠ The formation of the doctrine and the theory of Zhuodu
Object: Based on historical records and clinical experience to explore theorigin of the doctrine of the Zhuodu and principle-method-recipe-medicines,then put forward a new academic point of view and theoretical system.
Method: Comb in the record of ancient physicians in order to explore itsorigins, truthfully collection and preservation of the original name of the oldclinic experience of experts in medicine, Chinese medicine experts to establishthe unique name of the old clinic information database, forming TCM science,law, formula, drugs.
Result: Tease out the origins of the Zhuodu, investigate the toxic cloudhistory, pathogenic characteristics of the etiology and pathogenesis, voicedclinical symptoms, syndrome therapeutic principle, commonly usedprescription and drugs commonly used. Demonstrate the practicality of thedoctrine of the toxic cloud from the clinical.
Conclusion: The Zhuodu doctrine has perfect system, can be used toguide clinical practice.PartII2-year retrospective analysis for238patients with chronic
atrophic gastritis with pre-cancerous lesions in treatment of
huazhuo jiedu formula.
Object: Observe the mainly clinical manifestation, tongue and pulse ofthe precancerosis of chronic atrophic gastritis with the syndrome ofaccumulation of turbidity and toxicity，mainly by huazhuo jiedu，combinedwith individual differences identified (disease) permits the treatment of dialectical method.
Method:238cases diagnosed by endoscopy and pathology CAG withprecancerous lesions were retrospectively analyzed, and precancerous lesionsin36patients before and after their treatment reversed endoscopy andpathology were compared.
Result:1It was found that patients with chronic atrophic gastritis femaleones, multi-aged to elderly, with a low proportion of family history of cancer.Chronic atrophic gastritis cancer precursor lesions, dark tongue, greasy moss,pulse string smooth to permit the most common accumulation of turbidity andtoxicity tongue and pulse, which is consistent with clinical experience, thesymptoms of the presence of the top ten on the basis of their individualdifferences on the intrinsic syndrome, according to ten syndrome differentialtreatment.
2In238cases of patients with chronic atrophic gastritis, the totaleffective rate was79.0%, the total effective rate change endoscopy77.7%totaleffective rate of pathological changes of74.4%.
3The change of endoscopic type:Premalignant lesion in36patientsfollowed up front mucosa red and white, with white-based12cases, or evendisappear flattened folds, mucosal vascular revealed three cases, granular ornodular mucosa were17cases,17cases of erosion.
Premalignant lesion in36patients, follow-up mucosa red and white, withwhite-based10cases, or even disappear flattened folds, mucosal vascularrevealed five cases, granular or nodular mucosa were10cases,12cases oferosion.
4Premalignant lesion in36patients, moderate differences before thefollow-up6cases, mild abnormal increase in eight cases, seven cases ofsevere intestinal metaplasia, moderate intestinal metaplasia five cases,11cases of mild intestinal metaplasia, focal intestinal metaplasia5cases.
Premalignant lesion in36patients were followed up moderatelyabnormal increase0cases, mild abnormal increase in one case, severeintestinal metaplasia0cases, moderate intestinal metaplasia0cases,10cases of mild intestinal metaplasia, focal intestinal metaplasia1cases.
5Outcome of the situation of cancer: there is no cases of pre-cancerouslesions adenocarcinoma after Huazhuo jiedu therapy.
Conclusion: Chronic atrophic gastritis precancerous lesions, pathologicalall have metaplasia and (or) changes in intestinal epithelial dysplasia.Syndrome and microscopic pathology tongue dark greasy moss, pulse stringsmooth as chronic atrophic gastritis precancerous lesions accumulation ofturbidity and toxicity permit diagnosis is based, and according to individualdifferences in chronic atrophic gastritis in patients with pre-cancerous lesionscan appear ten major symptoms, huazhuo judu therapy in chronic atrophicgastritis cancer precursor lesions for treatment, according to the mainsymptom resolution (disease) permits the treatment, not only prominenthuazhuo jiedu characteristics, but also the principles of diagnosis andtreatment.
Part Ⅲ Effects of Huazhuojiedu Formula on115cases withprecancerosis of chronic atrophic gastritis and influence
on PG and hemorheology
Objective: To observe the therapeutic effects of Huazhuo jiedu Formulaon the precancerosis of chronic atrophic gastritis with the syndrome ofaccumulation of turbidity and toxicity,and the influence on the PG,hemorheology, and to explore its mechanism further.
Method: Treatment group: Given a daily Huazhuo Jiedu prescription,taken morning and evening empty stomach and daily.
Control group:Given a daily Weifuchun Tablet(WFCT),taken4pieceseach time,3times a day,before meals for30min.
Both groups were disabled other drugs for treating chronic gastric in thetreatment period and were treated for2courses,which included3months forone.
Result:1Comparison of clinical efficacy of the two groups
The total efficiency of treatment group was86.7%,the total efficiency ofcontrol group was67.2%.In the total efficiency,the difference was statistically significant(p<0.01)。
2Comparison of endoscopic and pathological efficacy of the two groups
Compared endoscopic efficacy of the two groups,there were significantdifference after statistical processing.The total efficiency of treatment groupwas85.0%,the total efficiency of control group was56.4%.Thus treatmentgroup was superior to control group(p<0.05).Compared pathological efficacyof the two groups,there were significant difference after statisticalprocessing.The total efficiency of treatment group was83.3%,the totalefficiency of control group was65.5%.Thus treatment group was superior tocontrol group(p<0.05).
Comparison of pepsinogen expression: In both groups, pepsinogenⅠincreased, pepsinogen II reduced after treating. In the treatment group,pepsinogenⅠwas108.32±17.27mPa·s before treating, was143.17±17.81mPa·s after treating; pepsinogen II was10.74±1.88mPa·s before treating,was7.48±1.69mPa·s after treating, therefore the difference was statisticallysignificant(p<0.05). In the control group, pepsinogen Ⅰ was104.92±15.17mPa·s before treating, was8.42±1.62mPa·s after treating, thus thedifference was statistically significant(p<0.05).After treatment,pepsinogen Ⅰin the treatment group increased more than it in the control group, thereforethe difference was statistically significant(p<0.05); pepsinogen II decreasedmore than it in the control group,thus the difference was statisticallysignificant(p<0.05).
4Comparison of hemorheology indexes before and after treatment inboth groups
Compared whole blood viscosity in the two groups before and aftertreatment, the difference was statistically significant(p<0.05). In the treatmentgroup, whole blood high shear viscosity values was5.95±0.89mPa s beforetreating, was3.74±0.37mPa s after treating; whole blood low shear viscosityvalues was5.95±0.89mPa s before treating, was15.35±1.11mPa s aftertreating.In the control group, whole blood high shear viscosity values was5.66±0.72mPa s before treating, was34.08±0.36mPa s after treating; whole blood low shear viscosity values was20.29±1.87mPa s before treating, was16.02±1.38mPa s after treating. After treatment, the improvement of wholeblood high shear viscosity values in the treatment group was superior tocontrol group(p<0.05), and the difference was statistically significant (p<0.05);changs of whole blood low shear viscosity values was not obvious,so therewas no statistically significant difference(p<0.05).
Conclusion:1Huazhuojiedu Formula can reduce the degree ofhyperemia and edema, erosion of gastric mucosal, alleviate gastroscope signs(such as mucosal play, hyperplasia of particles), and improve the cure rate ofpathology in patients with pre-cancerous lesions.
2When the body is in a state of chronic atrophic gastritis with intestinalmetaplasia and atypical hyperplasia, it can secret PG Ⅱ,which can result inrising of serum PG Ⅱ. That can damage the gastric mucosa, increase bloodviscosity and slow blood stream which is not conducive to the restoration ofgastric mucosa.
3Huazhuojiedu Formula may chang the environment condition of gastricmucosa by lowering the expression of pepsin Ⅱ and reducing bloodviscosity,thereby preventing the further development of pre-cancerous lesions,and even reversing them.
Part Ⅳ Influence of Huazhuojiedu Formula on gastric juicecomponents and GAS on the patients with precancerosisof chronic atrophic gastritis
Objective: To observe the influence of Huazhuojiedu Formula on gastricjuice components and GAS on the precancerosis of chronic atrophic gastritiswith the syndrome of accumulation of turbidity and toxicity.
Method: Treatment group:Given a daily Huazhuojiedu Formula, taken2times on an empty stomach in the morning and evening daily.
Control group:Given a daily Weifuchun Tablet(WFCT),taken4pieceseach time,3times a day,before meals for30min.
Both groups were disabled other drugs for treating chronic gastric in thetreatment period and were treated for2courses, which included3months for one.
Result:1Comparison of clinical efficacy of the two groups
The total efficiency of treatment group was80.0%,the total efficiency ofcontrol group was62.1%.In the total efficiency,the difference was statisticallysignificant(p<0.01)。
2Comparison of endoscopic and pathological efficacy of the two groups:
Compared efficacy of the two groups,there were significant differenceafter statistical processing.Compared endoscopic efficacy of the twogroups,the total efficiency of treatment group was81.7%,the total efficiencyof control group was75.9%.Thus treatment group was superior to controlgroup(p<0.05).Compared pathological efficacy of the two groups,the totalefficiency of treatment group was75.0%,the total efficiency of control groupwas62.1%.Thus treatment group was superior to control group(p<0.05).
3Comparison of gastric juice components of the two groups
Gastric juice components(such as free acid、total acid、lactic acid andnitrite）of the two groups were compared before and after treatment.Before thetreatment, compared the free acid、total acid, lactic acid and nitrite of the twogroups,there was no statistically significant difference(p>0.05). After thetreatment,the free acid and total acid in the gastric juice were improved thanbefore, and the treatment group increased more obviously than the controlgroup(p<0.05); lactic acid and nitrite decreased obviously than before, and thetreatment group decreased more obviously than the control group(p<0.05).
4Comparison of gastrin levels before and after treatment of the twogroups
Before treatment,compared the gastrin levels of the two groups,there wasno statistically significant difference(p>0.05).After treatment,the gastrin levelsof the two groups decreased than before,and the treatment group decreasedmore obviously than the control group(p<0.05).
Conclusion：1Huazhuojiedu Formula can reduce the degree ofhyperemia and edema, erosion of gastric mucosal, alleviate gastroscope signs,such as mucosal play, hyperplasia of particles, and improve the cure rate of pathology in patients with pre-cancerous lesions.
2The total acid and free acid of patients with precancerosis of chronicatrophic gastritis will decrease, and their nitrite and lactic acid will increase.The nitrite, as a common carcinogens,may promote the further development ofpre-cancerous lesions.The gastrin of the patients will increase reactivity, whichmay promote cellular differentiation and proliferation of patients withintestinal metaplasia or atypical hyperplasia.
3Huazhuojiedu Formula can promote the recovery of gastric mucosa,probably through decreasing the expression of gastrin, improving gastric juicecomponents and reducing lactic and nitrite, thereby, prevent the furtherdevelopment of precancerous lesions of gastric cancer.
目的：以历史文献记载及临床经验为依据探讨浊毒学说渊源及理法方药，进而提出新的学术观点及理论体系。
方法：梳理历代医家中对浊毒的记载，以探讨其源流，如实采集和原始保存名老中医药专家的诊疗经验，建立名老中医药专家独特诊疗信息数据库，形成浊毒学说的理法方药。
结果：梳理出浊毒的源流，探讨了浊毒的浊毒的历史沿革、病因病机致病特点、临床症候、治则治法、常用方剂、常用中药，从临床论证了浊毒学说的实用性。
结论：浊毒学说具有完善的理法方药体系，可用于指导临床实践。
第二部分238例慢性萎缩性胃炎伴癌前期病变患者应用化浊解毒方治疗2年回顾性分析
目的：探讨慢性萎缩性胃炎癌前期病变患者浊毒证的主要表现、舌脉，并以化浊解毒为主，结合个体差异，辨（症）证治疗的辨证方法。
方法：对238例经胃镜及病理诊断为CAG伴癌前期病变的门诊患者进行回顾性分析，并对癌前病变发生逆转的36例患者其治疗前后胃镜及病理进行比较。
结果：
1研究发现慢性萎缩性胃炎患者女性偏多，年龄以中老年为多，具有肿瘤家族史者比例偏低。慢性萎缩性胃炎癌前期病变患者，舌质暗、苔腻、脉弦细滑为浊毒证最常见舌脉，这也符合临床经验，十大症状在浊毒内蕴的基础上存在其个体差异，可根据十症（证）辨证治疗。
2在238例慢性萎缩性胃炎患者中，临床总有效率为79.0%，胃镜改变总有效率为77.7%，病理改变总有效率为74.4%。
3内镜下类型变化
癌前病变逆转的36例患者，随访前黏膜红白相间，以白为主12例，皱壁变平甚至消失，黏膜血管显露3例，黏膜呈颗粒或结节状17例，糜烂17例。
癌前病变逆转的36例患者，随访后黏膜红白相间，以白为主10例，皱壁变平甚至消失，黏膜血管显露5例，黏膜呈颗粒或结节状10例，糜烂12例。
4病理改变
癌前病变逆转的36例患者，随访前中度异增6例、轻度异增8例、重度肠化7例、中度肠化5例、轻度肠化11例、灶性肠化5例。
癌前病变逆转的36例患者，随访后中度异增0例、轻度异增1例、重度肠化0例、中度肠化0例、轻度肠化10例、灶性肠化1例。
5癌变的转归情况：癌前期病变经过化浊解毒治疗没有发生腺癌的病例。
结论：慢性萎缩性胃炎癌前期病变，病理均具有肠上皮化生和（或）不典型增生（上皮内瘤变）的改变。病理微观辨证及舌暗苔腻，脉弦细滑可以作为慢性萎缩性胃炎癌前期病变浊毒证诊断依据，在慢性萎缩性胃炎癌前期病变患者中并根据个体差异，可以出现十大主要症状，以化浊解毒治疗为大法对慢性萎缩性胃炎癌前期病变患者进行治疗，根据主要症状，辨（症）证治疗，既突出化浊解毒的特色，又不失辨证论治的原则。
第三部分化浊解毒方治疗慢性萎缩性胃炎癌前期病变115例临床观察及对PG、血流变的影响
目的：观察化浊解毒方治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴证患者的临床疗效及对PG、血流变的影响，并进一步探讨其机制。
方法：
治疗组：给予化浊解毒方(处方：白花蛇舌草15g、半枝莲15g、茵陈15g、黄连15g、藿香15g、全蝎9g、蜈蚣4g等),每日1剂。分早晚2次空腹服。
对照组：给予胃复春片，每次４片，每天３次，饭前30min服用。
两组在治疗时停用其他治疗慢性胃炎的药物。两组均以３个月为１个疗程，共治疗２个疗程。
结果：
1两组临床综合疗效比较
治疗组总有效率为86.7%，对照组总有效率为67.2%，两组患者总有效率比较差异有统计学意义(p<0.01)。
2两组内镜、病理疗效比较
内镜治疗组与对照组比较，经统计学处理，差异有显著性。治疗组总有效率为85.0%，对照组为56.4%，治疗组疗效明显为优(p<0.05)。病理治疗组与对照组比较，经统计学处理，差异有显著性。治疗组总有效率为83.3%，对照组为65.5%，治疗组疗效明显为优(p<0.05)。
3胃蛋白酶原表达情况比较
两组患者胃蛋白酶原治疗后胃蛋白酶原Ⅰ升高、胃蛋白酶原Ⅱ降低。治疗组治疗前胃蛋白酶原Ⅰ108.32±17.27mPa s，治疗后143.17±17.81mPa s；胃蛋白酶原Ⅱ治疗前10.74±1.88mPa s，治疗后7.48±1.69mPa s，差异有统计学意义(p<0.05)。对照组治疗前胃蛋白酶原Ⅰ104.92±15.17mPa s，治疗后胃蛋白酶原Ⅰ123.66±16.91mPa s；对照组治疗前胃蛋白酶原Ⅱ10.93±1.78mPa s，治疗后8.42±1.62mPa s，差异有统计学意义(p <0.05)。治疗后，治疗组胃蛋白酶原Ⅰ升高明显高于对照组，差异有统计学意义(p <0.05)，治疗组胃蛋白酶原Ⅱ降低明显高于对照组，差异有统计学意义(p <0.05)。
4两组患者治疗前后血液流变学指标比较
两组治疗前后全血粘度比较，差异均有统计学意义（p<0.05）。治疗组治疗前全血粘度高切值5.95±0.89mPa s，治疗后3.74±0.37mPa s，治疗组治疗前全血粘度低切值5.95±0.89mPa s，治疗后15.35±1.11mPa s；对照组治疗前全血粘度高切值5.66±0.72mPa s，治疗后全血粘度高切值4.08±0.36mPa s，对照组治疗前全血粘度低切值20.29±1.87mPa s，治疗后16.02±1.38mPa s。治疗后治疗组全血粘度高切值改善优于对照组，差异具有统计学意义（p<0.05）,全血粘度低切值改变不明显，差异无统计学意义（p>0.05）
结论：1化浊解毒方能减轻患者胃黏膜充血、水肿、糜烂，缓解黏膜白相、颗粒增生等胃镜征象，提高患者癌前期病变病理的治愈率。
2慢性萎缩性胃炎伴肠化、不典型增生（上皮内瘤变）时，因其分泌PGⅡ，可导致血清中PGⅡ上升，对胃黏膜产生破坏，血粘稠度常增高、血流缓慢不利于萎缩的黏膜的修复。
3化浊解毒方可能通过降低胃蛋白酶Ⅱ的表达及降低血粘稠度，改变胃黏膜环境状态，进而阻止癌前期病变的进一步发展，甚至逆转。第四部分化浊解毒方对慢性萎缩性胃炎胃癌前病变患者胃液成分及
GAS的影响
目的：观察化浊解毒法治疗慢性萎缩性胃炎胃癌前病变浊毒内蕴证患者的胃液成分及GAS的影响。
方法：
治疗组：给予化浊解毒方(处方：白花蛇舌草15g、半枝莲15g、茵陈15g、黄连15g、藿香15g、全蝎9g、蜈蚣4g等)，每日1剂。分早晚2次空腹服。
对照组：给予胃复春片，每次４片，每天３次，饭前30min服用。
两组在治疗时停用其他治疗慢性胃炎的药物。两组均以３个月为１个疗程，共治疗２个疗程。
结果：
1两组临床综合疗效比较
治疗组总有效率为80.0%，对照组总有效率为62.1%，两组患者总有效率比较差异有统计学意义(p <0.01)。
2两组内镜及病理疗效比较
治疗组与对照组比较，经统计学处理，差异有显著性。内镜治疗组总有效率为81.7%，对照组为75.9%，治疗组疗效明显为优(p <0.05)。病理治疗组总有效率为75.0%，对照组为62.1%，治疗组疗效明显为优(p<0.05)。
3两组胃液成分比较
对两组患者胃液中游离酸、总酸、乳酸及亚硝酸盐进行治疗前后的比较。治疗前，两组胃液中游离酸、总酸、乳酸及亚硝酸盐含量比较，差异无统计学意义（p>0.05）。治疗后，两组患者胃液中游离酸及总酸含量均较治疗前有所提高，与对照组比较，治疗组增加更为明显(p<0.05)；乳酸和亚硝酸盐含量较治疗前明显降低(p<0.05)，与对照组比较，治疗组乳酸下降更为明显，差异有统计学意义(p<0.05)。
4两组患者胃泌素水平治疗前后的比较
治疗前，两组胃泌素水平比较，差异无统计学意义（p>0.05）。治疗后，两组患者胃泌素水平均较治疗前有所降低，与对照组比较，治疗组降低更为明显(p<0.05)。
结论：1化浊解毒方能减轻患者胃黏膜充血、水肿、糜烂，缓解黏膜白相、颗粒增生等胃镜征象，提高患者癌前期病变病理的治愈率。
2慢性萎缩性胃炎癌前期病变患者总酸及游离酸含量降低，亚硝酸盐及乳酸升高，亚硝酸盐为常见的致癌物质，可能促进癌前期病变的进一步发展。胃泌素反应性升高，可能促进肠化或不典型增生（上皮内瘤变）的黏膜细胞的分裂增殖。
3化浊解毒方可能通过降低胃泌素表达，改善患者胃液成分，增加总酸及游离酸含量，降低乳酸及亚硝酸盐含量，促进胃黏膜的修复，阻止胃癌前病变进一步发展。
The zhuodu doctrine is an important doctrine proposed in recent years, tomake a contribution to the enrichment and development of traditional Chinesemedicine. The zhuodu doctrine derived from clinical practice, applied toclinical, should be tested and improved for real application. Precancerouslesion of chronic atrophic gastritis is the clinical common diseasefrequently-occurring disease. But the reverse atrophic and intestinalmetaplasia is yet to be further study, so it prompt us to expand way of thinking,research and development a new theory and method. And apply the drugs ofhuazhuojiedu to the therapy consciously, so the theory of zhuodu wereestablished, and clinical medication by syndrome differentiation. The theoryfor the treatment of chronic atrophic gastritis pre-cancerous lesions opens up anew train of thought. However, in all kinds of literature about the zhuoduscattered on the description of the zhuodu is all a lack of detailedunderstanding. In order to increase awareness of the doctrine, in the first part，the definition of zhuodu, development process of zhuodu, pathogene sis ofzhuodu, virulence characteristics of zhuodu, syndrome clinical manifestationsof zhuodu, treatment principles of zhuodu, common formula of zhuodu,Chinese medicine commonly used of zhuodu are Systematically discussed. Inthe second part, it is a retrospective analysis of medical records about the mainhuazhuo jiedu formula that treatment238cases of chronic atrophic gastritis inpatients with precancerous lesions, summarize the clinical efficacy and themain symptoms and tongue and pulse, establish the primary way of huazhuojiedu treatment, and according to individual differences determine the clinicalsyndrome treatment methods. In the third part, we observe the clinical efficacyof huazhuo jiedu formula on the precancerosis of chronic atrophic gastritis with the syndrome of accumulation of turbidity and toxicity, and observationof patients pepsinogen change, changes in hemorheology to chronic atrophicgastritis of precancerous lesions, to provide the material basis foraccumulation of turbidity and toxicity and its mechanism. In the fourth part,we observe the clinical efficacy of huazhuo jiedu formula on the precancerosisof chronic atrophic gastritis with the syndrome of accumulation of turbidityand toxicity, and observation the impact on the stomach secrete hormone whenpatients gastric juice change, and further explore its mechanism.
PartⅠ The formation of the doctrine and the theory of Zhuodu
Object: Based on historical records and clinical experience to explore theorigin of the doctrine of the Zhuodu and principle-method-recipe-medicines,then put forward a new academic point of view and theoretical system.
Method: Comb in the record of ancient physicians in order to explore itsorigins, truthfully collection and preservation of the original name of the oldclinic experience of experts in medicine, Chinese medicine experts to establishthe unique name of the old clinic information database, forming TCM science,law, formula, drugs.
Result: Tease out the origins of the Zhuodu, investigate the toxic cloudhistory, pathogenic characteristics of the etiology and pathogenesis, voicedclinical symptoms, syndrome therapeutic principle, commonly usedprescription and drugs commonly used. Demonstrate the practicality of thedoctrine of the toxic cloud from the clinical.
Conclusion: The Zhuodu doctrine has perfect system, can be used toguide clinical practice.PartII2-year retrospective analysis for238patients with chronic
atrophic gastritis with pre-cancerous lesions in treatment of
huazhuo jiedu formula.
Object: Observe the mainly clinical manifestation, tongue and pulse ofthe precancerosis of chronic atrophic gastritis with the syndrome ofaccumulation of turbidity and toxicity，mainly by huazhuo jiedu，combinedwith individual differences identified (disease) permits the treatment of dialectical method.
Method:238cases diagnosed by endoscopy and pathology CAG withprecancerous lesions were retrospectively analyzed, and precancerous lesionsin36patients before and after their treatment reversed endoscopy andpathology were compared.
Result:1It was found that patients with chronic atrophic gastritis femaleones, multi-aged to elderly, with a low proportion of family history of cancer.Chronic atrophic gastritis cancer precursor lesions, dark tongue, greasy moss,pulse string smooth to permit the most common accumulation of turbidity andtoxicity tongue and pulse, which is consistent with clinical experience, thesymptoms of the presence of the top ten on the basis of their individualdifferences on the intrinsic syndrome, according to ten syndrome differentialtreatment.
2In238cases of patients with chronic atrophic gastritis, the totaleffective rate was79.0%, the total effective rate change endoscopy77.7%totaleffective rate of pathological changes of74.4%.
3The change of endoscopic type:Premalignant lesion in36patientsfollowed up front mucosa red and white, with white-based12cases, or evendisappear flattened folds, mucosal vascular revealed three cases, granular ornodular mucosa were17cases,17cases of erosion.
Premalignant lesion in36patients, follow-up mucosa red and white, withwhite-based10cases, or even disappear flattened folds, mucosal vascularrevealed five cases, granular or nodular mucosa were10cases,12cases oferosion.
4Premalignant lesion in36patients, moderate differences before thefollow-up6cases, mild abnormal increase in eight cases, seven cases ofsevere intestinal metaplasia, moderate intestinal metaplasia five cases,11cases of mild intestinal metaplasia, focal intestinal metaplasia5cases.
Premalignant lesion in36patients were followed up moderatelyabnormal increase0cases, mild abnormal increase in one case, severeintestinal metaplasia0cases, moderate intestinal metaplasia0cases,10cases of mild intestinal metaplasia, focal intestinal metaplasia1cases.
5Outcome of the situation of cancer: there is no cases of pre-cancerouslesions adenocarcinoma after Huazhuo jiedu therapy.
Conclusion: Chronic atrophic gastritis precancerous lesions, pathologicalall have metaplasia and (or) changes in intestinal epithelial dysplasia.Syndrome and microscopic pathology tongue dark greasy moss, pulse stringsmooth as chronic atrophic gastritis precancerous lesions accumulation ofturbidity and toxicity permit diagnosis is based, and according to individualdifferences in chronic atrophic gastritis in patients with pre-cancerous lesionscan appear ten major symptoms, huazhuo judu therapy in chronic atrophicgastritis cancer precursor lesions for treatment, according to the mainsymptom resolution (disease) permits the treatment, not only prominenthuazhuo jiedu characteristics, but also the principles of diagnosis andtreatment.
Part Ⅲ Effects of Huazhuojiedu Formula on115cases withprecancerosis of chronic atrophic gastritis and influence
on PG and hemorheology
Objective: To observe the therapeutic effects of Huazhuo jiedu Formulaon the precancerosis of chronic atrophic gastritis with the syndrome ofaccumulation of turbidity and toxicity,and the influence on the PG,hemorheology, and to explore its mechanism further.
Method: Treatment group: Given a daily Huazhuo Jiedu prescription,taken morning and evening empty stomach and daily.
Control group:Given a daily Weifuchun Tablet(WFCT),taken4pieceseach time,3times a day,before meals for30min.
Both groups were disabled other drugs for treating chronic gastric in thetreatment period and were treated for2courses,which included3months forone.
Result:1Comparison of clinical efficacy of the two groups
The total efficiency of treatment group was86.7%,the total efficiency ofcontrol group was67.2%.In the total efficiency,the difference was statistically significant(p<0.01)。
2Comparison of endoscopic and pathological efficacy of the two groups
Compared endoscopic efficacy of the two groups,there were significantdifference after statistical processing.The total efficiency of treatment groupwas85.0%,the total efficiency of control group was56.4%.Thus treatmentgroup was superior to control group(p<0.05).Compared pathological efficacyof the two groups,there were significant difference after statisticalprocessing.The total efficiency of treatment group was83.3%,the totalefficiency of control group was65.5%.Thus treatment group was superior tocontrol group(p<0.05).
Comparison of pepsinogen expression: In both groups, pepsinogenⅠincreased, pepsinogen II reduced after treating. In the treatment group,pepsinogenⅠwas108.32±17.27mPa·s before treating, was143.17±17.81mPa·s after treating; pepsinogen II was10.74±1.88mPa·s before treating,was7.48±1.69mPa·s after treating, therefore the difference was statisticallysignificant(p<0.05). In the control group, pepsinogen Ⅰ was104.92±15.17mPa·s before treating, was8.42±1.62mPa·s after treating, thus thedifference was statistically significant(p<0.05).After treatment,pepsinogen Ⅰin the treatment group increased more than it in the control group, thereforethe difference was statistically significant(p<0.05); pepsinogen II decreasedmore than it in the control group,thus the difference was statisticallysignificant(p<0.05).
4Comparison of hemorheology indexes before and after treatment inboth groups
Compared whole blood viscosity in the two groups before and aftertreatment, the difference was statistically significant(p<0.05). In the treatmentgroup, whole blood high shear viscosity values was5.95±0.89mPa s beforetreating, was3.74±0.37mPa s after treating; whole blood low shear viscosityvalues was5.95±0.89mPa s before treating, was15.35±1.11mPa s aftertreating.In the control group, whole blood high shear viscosity values was5.66±0.72mPa s before treating, was34.08±0.36mPa s after treating; whole blood low shear viscosity values was20.29±1.87mPa s before treating, was16.02±1.38mPa s after treating. After treatment, the improvement of wholeblood high shear viscosity values in the treatment group was superior tocontrol group(p<0.05), and the difference was statistically significant (p<0.05);changs of whole blood low shear viscosity values was not obvious,so therewas no statistically significant difference(p<0.05).
Conclusion:1Huazhuojiedu Formula can reduce the degree ofhyperemia and edema, erosion of gastric mucosal, alleviate gastroscope signs(such as mucosal play, hyperplasia of particles), and improve the cure rate ofpathology in patients with pre-cancerous lesions.
2When the body is in a state of chronic atrophic gastritis with intestinalmetaplasia and atypical hyperplasia, it can secret PG Ⅱ,which can result inrising of serum PG Ⅱ. That can damage the gastric mucosa, increase bloodviscosity and slow blood stream which is not conducive to the restoration ofgastric mucosa.
3Huazhuojiedu Formula may chang the environment condition of gastricmucosa by lowering the expression of pepsin Ⅱ and reducing bloodviscosity,thereby preventing the further development of pre-cancerous lesions,and even reversing them.
Part Ⅳ Influence of Huazhuojiedu Formula on gastric juicecomponents and GAS on the patients with precancerosisof chronic atrophic gastritis
Objective: To observe the influence of Huazhuojiedu Formula on gastricjuice components and GAS on the precancerosis of chronic atrophic gastritiswith the syndrome of accumulation of turbidity and toxicity.
Method: Treatment group:Given a daily Huazhuojiedu Formula, taken2times on an empty stomach in the morning and evening daily.
Control group:Given a daily Weifuchun Tablet(WFCT),taken4pieceseach time,3times a day,before meals for30min.
Both groups were disabled other drugs for treating chronic gastric in thetreatment period and were treated for2courses, which included3months for one.
Result:1Comparison of clinical efficacy of the two groups
The total efficiency of treatment group was80.0%,the total efficiency ofcontrol group was62.1%.In the total efficiency,the difference was statisticallysignificant(p<0.01)。
2Comparison of endoscopic and pathological efficacy of the two groups:
Compared efficacy of the two groups,there were significant differenceafter statistical processing.Compared endoscopic efficacy of the twogroups,the total efficiency of treatment group was81.7%,the total efficiencyof control group was75.9%.Thus treatment group was superior to controlgroup(p<0.05).Compared pathological efficacy of the two groups,the totalefficiency of treatment group was75.0%,the total efficiency of control groupwas62.1%.Thus treatment group was superior to control group(p<0.05).
3Comparison of gastric juice components of the two groups
Gastric juice components(such as free acid、total acid、lactic acid andnitrite）of the two groups were compared before and after treatment.Before thetreatment, compared the free acid、total acid, lactic acid and nitrite of the twogroups,there was no statistically significant difference(p>0.05). After thetreatment,the free acid and total acid in the gastric juice were improved thanbefore, and the treatment group increased more obviously than the controlgroup(p<0.05); lactic acid and nitrite decreased obviously than before, and thetreatment group decreased more obviously than the control group(p<0.05).
4Comparison of gastrin levels before and after treatment of the twogroups
Before treatment,compared the gastrin levels of the two groups,there wasno statistically significant difference(p>0.05).After treatment,the gastrin levelsof the two groups decreased than before,and the treatment group decreasedmore obviously than the control group(p<0.05).
Conclusion：1Huazhuojiedu Formula can reduce the degree ofhyperemia and edema, erosion of gastric mucosal, alleviate gastroscope signs,such as mucosal play, hyperplasia of particles, and improve the cure rate of pathology in patients with pre-cancerous lesions.
2The total acid and free acid of patients with precancerosis of chronicatrophic gastritis will decrease, and their nitrite and lactic acid will increase.The nitrite, as a common carcinogens,may promote the further development ofpre-cancerous lesions.The gastrin of the patients will increase reactivity, whichmay promote cellular differentiation and proliferation of patients withintestinal metaplasia or atypical hyperplasia.
3Huazhuojiedu Formula can promote the recovery of gastric mucosa,probably through decreasing the expression of gastrin, improving gastric juicecomponents and reducing lactic and nitrite, thereby, prevent the furtherdevelopment of precancerous lesions of gastric cancer.
引文
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