【作者】 曹志群；

【导师】 隗继武；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2002， 博士

【摘要】 目的：本研究旨在运用中医辨证论治理论从临床和实验方面对慢性萎缩性胃炎癌前病变的病因病机和治法方药进行深入的探讨，以寻求治疗本病的中医药效机理。方法：根据临床辨证，提出慢性萎缩性胃炎痛前病变之脾胃虚损，瘀毒内蕴，穷必及肾说，拟健脾益肾、行气化瘀、敞结解毒为治法。据此遣药组方，用现代工艺流程制成芪莲舒痞颗粒（QLSP）。临床治疗慢性萎缩性胃炎癌前病变61例，并与40例胃复春，36例维酶素对照组进行临床和病理疗效比较。同时观察QLSP组及二对照组治疗前后H·Pylori清除率、血cAMP、SOD、LPO、TXB₂、6-K-PGF_1α的变化。实验研究用致癌剂造Wistar大鼠胃癌前病变模型，运用分子生物学原位杂文法、免疫组化法等技术，检测治疗前后QLSP组与二对照组大鼠胃粘膜癌前病变血管生成因子（VEGF及受体、bFGF、PDGF等）、MVD表达与病理学改变、血清SOD、MDA的变化以及免疫器官（胸腺、肿）的重量变化。结果：临床研究QLSP组治疗前后显效率32.8％，总行效率80.3％；胃复春组显效率27.5％，总有效率70.0％：维酶素组显效率2.8％，总有效率47.2％；QLSP组有效率有效率明显高于二对照组。QLSP组抑制H·Pylori，升高血cAMP、SOD，降低LPO，改善TXB₂/6-K-PGF_1α，与二对照组有显著差异（p＜0.05）。实验研究表明，胃粘膜癌前病变也有血管生成因子表达，与正常组有明显差异（p＜0.05）。QLSP组能明显抑制血管生成因子（VEGF及受体、bFGF、PDGF等）的表达和分泌；升高血清SOD、降低MDA；阻断或逆转胃粘膜癌前病变的病理状态；明显增加胸腺、脾的重量，并且与对照组有明显差异（p＜0.05）。结论：脾胃虚损，瘀毒内蕴，穷必及肾是慢性萎缩性胃炎癌前病变的主要病机。因此，健脾益肾，行气化瘀，散结解毒是其重要的治法，QLSP治疗本病不但有较好的临床疗效，而且结合实验研究，从整体、细胞和分子水平上揭示了本方治疗慢性萎缩性胃炎癌前病变的作用机制。认为该药作用于该病的多个环节，多个靶点，具有综合疗效作用，其机则可能与抑制血管生成因子、抗氧化、抑制脂质过氧化、调节免疫、改善血液PG1₂/TXA₂平衡、抑制H·D1叮、抗炎等综合作用有关，特别是其抑制血管牛成因于的表达，对本病的治疗提供了新的研究思路。为丰富慢性萎缩性胃炎癌汕病变的病理学和治疗学的内涵，做出了有益的尝试。更多还原

【Abstract】 OBJECTIVE In the study ,the TCM theories of treatment according to syndrome differentiation were used clinically and experimentally to probe into the possible causes, pathogenesis, management method and prescription of precancerous lesions of chronic atrophic gastritis,and to find out the pharmacodynamic mechanism of the prescription.METHODS On the basis of clinical syndrom differentiation,we come to the conclusion that the precancerous lesions of chronic atrophic gastritis are resulted from splenogastric asthenia,accumulation of stagnant pathogenic factors in the body,and involvement of the kidney functions at the advanced stage.Accordingly,we adopted the treatment principles of invigorating spleen and tonifying kidney,regulating qi to disperse stagnation,and dispersing accumulation of pathogenic factors to resolve masses.Guided by these principles we made up a prescription of medicinal herbs,which are processed and prepared with modern technique into granules named Qilian Shupi Granule(QLSP).61 patients of precancerous lesions of chronic atrophic gastritis were treated with QLSP Granule,and the clinical and pathological effects were compared with those of the 40 patients treated with Wei Fuchun Tablet and 36 patients treated with Weimeisu.At the same time, the Hp-eradicating rates, and the change of cAMP, SOD,LPO,TXB2,6-K-PGF0 inblood of the experinmental group were observed.In experiments,models of precancerous lesions of gastric cancer were induced by cancerogenic agent in Wistar rats,and in situ hybridizational and immunohistochemical methods were used to monitor angiogenesis factors (VEGF,VEGFR,bFGF, PDGF and so on)and MVD’s expression and pathological changes, the changes of SOD and LPO in plasma,and the weight changes of immune organs(thymus and spleen)in the QLSP group and the two control groups before and after treatment.RESULTS DATA of clinical research showed that in QLSP group the notable effective rate was 32.8%,and the total effective rate was 80.3%,while the notable effective rate was 27.5% and the total effective rate was 70.0% in Wei Fuchun group,and those of Weimeisu group was 2.8% and 47.2% respectively.The effective rate of QLSP being significantly higher than the other two drugs. It has been found that QLSP granule can inhibit Hp,rais cAMP and SOD in blood, lower MDA and improve TXB2/6-K-PGF|0, and the difference with the other two drugs is remarkable.Animal experimental research showed that precancerous lesions of gastric mucosa also has angiogenesis factors’ expression and the significant difference is compared with the control groups(p<0.05).QLSP Granule can notably inhibit the expression and secretion of angiogenesis factors (VEGF,VEGFR, bFGF,PDGF and so on),raise SOD in plasma,lower MDA,stop or reverse the pathological process of precancerous lesions of gastric mucosa,and considerably increase the weight of thyinus and spleen,and there was significant difference between the QLSP group and the two control groups(p<0.05).CONCLUSIONS Splenogastric asthenia,accumulation of stagnant pathogenic factors in the body, and involvement of the kidney functions at the advanced stage are the main causes leading to the pathogenesis of precancerous lesions of chronic atrophic gastritis.Therefore,invigorating spleen and tonifying kidney, regulating qi to disperse stagnation,and dispersing accumulation of pathogenic factors to resolve masses are the principles in the management of the conditon.The excellent clinical effect of QLSP together with the data from experimental research reveal itsmechanism at the systemic,cellular and molecular levels in treating precancerous lesions of chronic atrophic gastritis.The QLSP prescription acts on many chains and targets of the disease to produce a comprehensive therapeutic effect,the therapeutic mechanism may have much to do with an overall effect o inhibition of angiogenesis factors and lipid peroxidation,antioxidation, regulation of immunity,improvement of the balance between PG\2 and TXAi in blood,inhibition of Hp and anti-inflammatio更多还原