仁术健胃颗粒治疗慢性萎缩性胃炎癌前病变的临床与实验研究

【作者】 陆为民；

【导师】 单兆伟；

【作者基本信息】 南京中医药大学 ， 中医内科学， 2001， 博士

【摘要】 文献研究：从古今两方面深入探讨了中医对CAG癌前病变病名、病因病机、治则治法的认识，回顾了CAG癌前病变分子生物学及动物模型的研究状况，为本课题的临床和实验研究奠定了基础。 临床研究：190例CAG癌前病变属气虚血瘀热郁的患者随机分为两组，分别予仁术健胃颗粒与胃复春片口服，治疗6个月。结果显示，治疗组综合疗效及愈显率（基本治愈显效率）分别为91.4％、69.5％，临床疗效为93.0％，胃镜、萎缩、肠化、异型增生的有效率分别为70.1％、64.1％、66.4％、67.9％，Hp cagA基因阴转率为64.2％，且能显著改善胃镜征象，降低临床症状、萎缩、肠化、异型增生、肠化亚型、CEA、PCNA、AgNOR、Bc1-2及P53蛋白表达的积分值和血清一氧化氮（NO）含量，作用明显优于胃复春对照组（P＜0.01，0.05）。 实验研究：结果显示，仁术健胃颗粒能显著抑制多种诱变剂3，4苯并芘（BaP）、柔红霉素（DRN）、二甲基苯蒽（DMBA）、甲硝基亚硝基胍（MNNG）诱发的His—鼠伤寒沙门氏菌TA₉₈、TA₁₀₀回复突变，降低环磷酰胺（CPA）诱发的小鼠骨髓嗜多染红细胞（PCEs）微核的形成率，使含巴豆油的混合致炎剂诱发的小鼠耳肿胀减轻，明显抑制巴豆油诱发的小鼠背部表皮组织鸟氨酸脱羧酶（ODC）活性增高。此外，仁术健胃颗粒可明显降低由3—MCA和TPA联合所致Balb/3T3恶性细胞转化灶形成的数目及Balb/3T3恶性转化细胞在软琼脂中形成克隆的能力，与阳性对照组差异有显著性（P＜0.05）。 讨论：对CAG癌前病变的病机进行了深入的探讨，认为脾胃气虚是其本，血瘀热郁为其标，气虚、血瘀、热郁三者互为因果，恶性循环，是CAG→肠化→异型增生→胃癌多步骤癌变的关键，治疗应以益气活血清热为大法，并提出了其临床运用的基本原则。有关仁术健胃颗粒治疗CAG癌前病变的作用机理，可能与诱导和促进细胞的分化成熟、抑制细胞的异常增殖、抑制癌基因的活化和抑癌基因的失活、促进胃癌前细胞的调亡、根除Hp、减轻和削弱Hp毒力、抗致突变、抗促癌、抗化学致癌及调节血清NO水平等多因素有关。更多还原

【Abstract】 Review This thesis had reviewed the concept of chronic atrophic gastritis(CAG) precancerous lesion in traditional Chinese medicine. The aetiology, pathology, treatment principal and treatment method were discussed at the same time. Besides of these, this thesis also reviewed the modem research results of the molecular biology and animal models on the CAG precancerous lesion. All these established clinical and experimental foundation of this project.Clinical research: 190 cases of CAG precancerous lesion with Qi deficiency, blood stasis and heat accumulation were divided into two groups randomly . One group accepted the treatment of RENZHUJIANWEI Granual(RZJWG), the other accepted WEIFUCHUN Tablet(WFCT) as control. The whole duration of treatment was 6 months. The results indicated that the total effective rate and curative rate was 91.4% and 69.5% respectively. The clinical effective rate was 93.0%, The effective rate of gastroscope appearance~ atrophy, intestinal metaplasia and dysplasia were 70.1%, 64.1%, 66.4% and 67.9%~ 64.2% of the helicobacter pylori(Hp) cagA became negative after treatment. The score of CEA, PCNA, AgNOR, Bcl-2, P53 and the serological level of nitric oxide(NO) decreased significantly after treatment. All these effects of RZJWG were better than WFCT significantly (PKO.01,0.05).Experimental research: RZJWG could restrain obviously the back mutation of His-mice salmonella typhi TA98, TA 100 induced by several mutagenesis agents (3,4 benzopyrene, DRN, DMBA, MNNG). The micronuleus formation rate of PCES induced by cyclophosphamide (CPA) in mice marrow decreased too. It also could alleviate the auricular tumefaction of mice induced by mixed phlogogen which contained crotonarin and inhibit the activity of ornithine decarboxylase (ODC) induced by crotonarin in the epidermis tissue of mice back. In addition, RZJWG could decrease the number of Balb/3T3 malignant cell transformation focuses induced by 3-MCA and TPA, it also could inhibit the formation of Balb/3T3-4-98t~E~Li~malignant transforming cells clone in the soft agar. There were significant differences between RZJWG and positive controls(P<O.05).Discussion:The Qi deficiency of spleen and stomach is the basis of CAG precancerous lesion. While the blood stasis and heat accumulation are the secondary aspects of the aetiology. Qi deficiency, blood stasis and heat accumulation showed cause and effect relationship between them and form a vicious circle. This circle is the key point of CAG棐.intestinal metaplasia?dysplasia---~-gastric cancer. The treatment principle is invigorating Qi, activating blood and cooling heat. The thesis also put forward its basic method in clinical exertion. The mechanism of RZJWCI treating CAG precancerous lesion may be related to inducing and promoting cells differentiation, inhibiting abnormal proliferation, inhibiting activation of oncogene and inactivating suppressor gene, promoting apoptosis of precancerous cells, eliminating Hp and weakening its toxicity, opposing the cause of mutation, countering the cause of cancer, inhibiting chemical carciogenesis and regulating serum NO levels更多还原