化浊解毒和胃方对胃癌前病变大鼠VEGF、EGF表达的影响
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摘要
目的:通过观察化浊解毒和胃方对胃癌前病变(GPL)大鼠模型一般状况、胃粘膜形态学、血管内皮生长因子(VEGF)、内皮生长因子(EGF)表达的影响,试图探讨: (1)胃癌前病变与VEGF、EGF的表达的关系;(2)化浊解毒和胃方对胃癌前病变大鼠VEGF、EGF表达的影响,及其治疗胃癌前病变的现代医学内涵是否通过干预VEGF、EGF的表达,达到抗血管新生的作用,从而阻断和逆转胃癌前病变。为中医药治疗胃癌前病变提供一定的实验基础,为进一步研究化浊解毒和胃方治疗胃癌前病变奠定基础。?
方法:将六周龄SPF级健康Wistar雄性大鼠70只,用随机数字表法抽取10只作为正常对照组(简称正常组),余下的60只大鼠采用综合造模法造模,共24周。造模成功后,将造模组剩余大鼠按照随机原则分为5组:模型组,化浊解毒和胃方高、中、低剂量组,维甲酸组,每组9只老鼠。造模结束后各组进行相应治疗,共16周,于第40周处死大鼠。观察各组大鼠的精神、食欲、毛色和大便等情况,观察胃粘膜病理组织学的改变,放射免疫法测定EGF的表达,免疫组化法检测VEGF的表达。经统计分析比较各组间的差异, P<0.05有统计学意义。
结果:(1)一般情况:各治疗组均可改善胃癌前病变大鼠的毛色、精神状态、食欲、大便及活动度。其中化浊解毒和胃方各剂量组改善情况优于维甲酸组,但仍不如正常组。(2)病理形态学观察肉眼所见:正常组胃粘膜呈粉红色,粘膜皱襞表面光滑规整,伸展性好,未见增生结节;模型组粘膜呈灰白色,可见点状或片状出血,皱襞低平、稀少、甚至消失,胃壁弹力减弱,可见增生结节;维甲酸组粘膜较暗淡,较正常粘膜变薄,未见增生结节;高、中、低剂量组,除个别可见胃标本大体观显示胃壁弹力减弱,胃窦粘膜层变薄,色苍白,皱襞变平或走向紊乱,可见不同程度的陈旧性出血点,伴点状或灶状糜烂,大部分接近正常组。(3)胃粘膜病理组织学光学显微镜所见:改善模型大鼠胃粘膜方面,与模型组相比,化浊解毒和胃高、中、低剂量组及维甲酸组均能改善病变大鼠的胃粘膜,但化浊解毒和胃各剂量组优于维甲酸组。结果表明化浊解毒和胃方对大鼠胃癌前病变有较好的治疗作用。(4)血清EGF的表达:正常组、维甲酸组、低剂量组、中剂量组、高剂量组大鼠血清中EGF含量明显低于模型组,差异有统计学意义(P<0.05)。低剂量组、中剂量组、高剂量组与模型组比较,血清EGF的含量低于模型组,差异有统计学意义(P<0.05)。低剂量组、中剂量组、高剂量组与维甲酸组比较,血清EGF的含量低于维甲酸组,差异有统计学意义(P<0.05)。低、中、高剂量各组间比较无显著性差异(P>0.05)。提示化浊解毒和胃方高、中、低各剂量及维甲酸均对胃癌前病变大鼠血清EGF的表达有抑制作用,化浊解毒和胃方对EGF的抑制作用优于维甲酸,化浊解毒和胃方高、中、低剂量对EGF的抑制作用无差别。化浊解毒和胃方对EGF的表达有明显的抑制作用。(5)胃粘膜中VEGF的表达:正常组VEGF表达甚微,模型组VEGF表达较强烈,两组比较有显著异(P<0.05),提示VEGF在胃癌前病变中明显表达。与模型组比较,高、中、低剂量组VEGF的表达低于模型组,差异有显著性(P<0.05),提示化浊解毒和胃方具有明显抑制VEGF表达的作用。维甲酸组与模型组比较也存在显著差异(P<0.05)。高、中、低剂量组与维甲酸组比较均有显著差异(P<0.05),高剂量组、中剂量组与低剂量组比较无显著性差异(P>0.05),提示化浊解毒和胃方虽对VEGF有抑制作用,但不存在明显的量效关系。
结论:(1)EGF、VEGF在胃癌前病变中呈高表达。(2)化浊解毒和胃方可以改善胃癌前病变大鼠模型的一般状况。(3)化浊解毒和胃方可以改善胃癌前病变大鼠模型胃粘膜的损伤。(4)化浊解毒和胃方可抑制EGF、VEGF的表达,从而阻断或逆转胃癌前病变。其作用机制可能是通过抑制EGF、VEGF的表达,达到抗血管新生的作用,从而阻断或逆转胃癌前病变。
Objective:By observing the impact of HuaZhuoJeDuHeWei Decoction on Gastic Precancerous Lesions model rat’s general situation、gastric mucosal morphology、vascular endothelial growth factor(VEGF)、endothelial growth factors(EGF),attempt to explore:(1)the relationship between gastic precancerous lesions and the expression of VEGF、EGF;(2) effect of HuaZhuoJieDuHeWei Decoction on the expression of VEGF、EGF, and if its western medicine connotation of the treatment of gastic precancerous lesions is to inhibit angiogenesis by interferring the expression of VEGF、EGF, thereby blocking and reversing gastic precancerous lesions.and lay some experimental foundation for the treatment of gastic precancerous lesions by Chinese traditional medicine , and lay the foundation for further study of HuaZhuoJieDuHeWei Decoction.
Method:?70 SPF level healthy 6-week-old Wistar male rats, Drawn 10 with random number table as normal control group (normal group for short), The remaining 60 rats were modeled by integrated modeling method for 24 weeks. After the model been successfully built,.ratsrandomly divided the left rats into five group:model group, HuaZhuoJeDuHeWei Decoction high dose group,HuaZhuoJeDuHeWeiDecoction middle dose group,HuaZhuoJeDuHeWei Decoction low dose group, RetinoicAcid group,Each group with 9 rats. After modeling each group was treated accordingly for 16 weeks, the rats were killed in the first 40 weeks. Observe the spirit, loss of appetite, coat color and stool of rats in each group and so on, Observe pathology of gastric mucosa tissue , Measured the expression of EGF by radioimmunoassay, Immunohistochemistry was used to detect the expression of VEGF. the differences between the groups were drawn by statistical analysis, P<0.05?means the difference is statistically significant.?
Result:?(1)General condition of the rats:All the group of treatment can improve gastic precancerous lesions rats’fur color,the state of mind,the appetite,and the activity. HuaZhuoJeDuHeWei Decoction each dose group superior to improving the situation than Retinoic Acid group, but not as a normal group.(2)Observe the gastric mucosa by eyes:Gastric mucosa surface of normal group is pink, smooth, regularity. stretching is well, no hyperplastic nodules; The mucous of the model group is pale and point shape or schistose bleeds,Plica are low,rare and even disappear. stomach stretch weakened , hyperplastic nodule are visible; The mucous of the Retinoic Acid group is less pale and thin than normal group, no hyperplastic nodules;In high, middle and low-dose group, except for the general view of the stomach specimens, a few showed elastic stomach weakened, gastric mucous thinner, color pale, flattened folds or move toward disorder, we can see different levels of old bleeding points, with points, or stove-like erosion, most close to the normal group.(3)Gastric mucosa under light microscope observation: compared with model group, HuaZhuoJeDuHeWei Decoction high、middle、low-dose group and Retinoic Acid group can improve gastric mucosal lesions in rats,but the improvement of Retinoic Acid group is not as good as the HuaZhuoJeDuHeWei Decoction each dose group. The results showed that HuaZhuoJeDuHeWei Decoction has better therapeutic effection of gastric precancerous lesions in rats.(4) The expression of serum EGF: The normal group, Retinoic Acid group, low-dose group, middle-dose group, high-dose of serum EGF concentration was significantly lower than model group, the difference was statistically significant (P<0.05). Compared with model group, low-dose group, middle-dose group and high-dose group had a lower level of serum EGF, the difference was statistically significant(P<0.05).The difference between low-dose group, middle dose group, high-dose group and the Retinoic Acid group was statistically significant (P<0.05). Low、middle、high of the various groups showed no significant difference(P>0.05). It was pointed out that HuaZhuoJeDuHeWei Decoction each dose group and Retinoic Acid group can inhibit the expression of serum EGF,but HuaZhuoJeDuHeWei Decoction had better effection than Retinoic Acid, the inhabition of expression of EGF had no difference among the HuaZhuoJeDuHeWei Decoction high, middle and low-doses. HuaZhuoJeDuHeWei Decoct could significantly inhibited expression of EGF. (5) The expression of gastric mucosa VEGF : Little VEGF expressed in the normal group,while relatively strong expressed in the model group, the two groups were significantly different (P<0.05), VEGF was obviously expressed in gastic precancerous lesions . Compared with model group, high, middle and low-dose group had lower expression of VEGF, the difference was significant (P<0.05),which showed that HuaZhuoJeDuHeWei Decoct had a role of inhabiting the expression of VEGF.?There was also significant differences between Retinoic acid group and modlegroup(P<0.05). High, middle and low-dose group and the Retinoic Acid group were significantly different (P<0.05), high-dose group, middle- dose group and low- dose group showed no significant difference (P>0.05), which showed that HuazhuoJieDuHeWei Decoct could inhabit the expression of VEGF,but there was no obvious dose-response relationship.
Conclusion:(1)There is a high expression of EGF, VEGF in the gastic precancerous lesions.(2)HuaZhuoJieDuHeWeiDecoction can improve general state of rat model of gastic precancerous lesions.(3) HuaZhuoJieDuHeWei Decoction can improve impaired gastric mucosa of rat model of gastic precancerous lesions. (4) HuaZhuoJieDuHeWei Decoction can inhabit the expression of EGF、VEGF, thereby blocking and reversing gastic precancerous lesions.? The mechanism could be block and reverse gastic precancerous lesions through inhabiting the expression of VEGF、EGF, blocking the stomach ailments or reversed.
方法:将六周龄SPF级健康Wistar雄性大鼠70只,用随机数字表法抽取10只作为正常对照组(简称正常组),余下的60只大鼠采用综合造模法造模,共24周。造模成功后,将造模组剩余大鼠按照随机原则分为5组:模型组,化浊解毒和胃方高、中、低剂量组,维甲酸组,每组9只老鼠。造模结束后各组进行相应治疗,共16周,于第40周处死大鼠。观察各组大鼠的精神、食欲、毛色和大便等情况,观察胃粘膜病理组织学的改变,放射免疫法测定EGF的表达,免疫组化法检测VEGF的表达。经统计分析比较各组间的差异, P<0.05有统计学意义。
结果:(1)一般情况:各治疗组均可改善胃癌前病变大鼠的毛色、精神状态、食欲、大便及活动度。其中化浊解毒和胃方各剂量组改善情况优于维甲酸组,但仍不如正常组。(2)病理形态学观察肉眼所见:正常组胃粘膜呈粉红色,粘膜皱襞表面光滑规整,伸展性好,未见增生结节;模型组粘膜呈灰白色,可见点状或片状出血,皱襞低平、稀少、甚至消失,胃壁弹力减弱,可见增生结节;维甲酸组粘膜较暗淡,较正常粘膜变薄,未见增生结节;高、中、低剂量组,除个别可见胃标本大体观显示胃壁弹力减弱,胃窦粘膜层变薄,色苍白,皱襞变平或走向紊乱,可见不同程度的陈旧性出血点,伴点状或灶状糜烂,大部分接近正常组。(3)胃粘膜病理组织学光学显微镜所见:改善模型大鼠胃粘膜方面,与模型组相比,化浊解毒和胃高、中、低剂量组及维甲酸组均能改善病变大鼠的胃粘膜,但化浊解毒和胃各剂量组优于维甲酸组。结果表明化浊解毒和胃方对大鼠胃癌前病变有较好的治疗作用。(4)血清EGF的表达:正常组、维甲酸组、低剂量组、中剂量组、高剂量组大鼠血清中EGF含量明显低于模型组,差异有统计学意义(P<0.05)。低剂量组、中剂量组、高剂量组与模型组比较,血清EGF的含量低于模型组,差异有统计学意义(P<0.05)。低剂量组、中剂量组、高剂量组与维甲酸组比较,血清EGF的含量低于维甲酸组,差异有统计学意义(P<0.05)。低、中、高剂量各组间比较无显著性差异(P>0.05)。提示化浊解毒和胃方高、中、低各剂量及维甲酸均对胃癌前病变大鼠血清EGF的表达有抑制作用,化浊解毒和胃方对EGF的抑制作用优于维甲酸,化浊解毒和胃方高、中、低剂量对EGF的抑制作用无差别。化浊解毒和胃方对EGF的表达有明显的抑制作用。(5)胃粘膜中VEGF的表达:正常组VEGF表达甚微,模型组VEGF表达较强烈,两组比较有显著异(P<0.05),提示VEGF在胃癌前病变中明显表达。与模型组比较,高、中、低剂量组VEGF的表达低于模型组,差异有显著性(P<0.05),提示化浊解毒和胃方具有明显抑制VEGF表达的作用。维甲酸组与模型组比较也存在显著差异(P<0.05)。高、中、低剂量组与维甲酸组比较均有显著差异(P<0.05),高剂量组、中剂量组与低剂量组比较无显著性差异(P>0.05),提示化浊解毒和胃方虽对VEGF有抑制作用,但不存在明显的量效关系。
结论:(1)EGF、VEGF在胃癌前病变中呈高表达。(2)化浊解毒和胃方可以改善胃癌前病变大鼠模型的一般状况。(3)化浊解毒和胃方可以改善胃癌前病变大鼠模型胃粘膜的损伤。(4)化浊解毒和胃方可抑制EGF、VEGF的表达,从而阻断或逆转胃癌前病变。其作用机制可能是通过抑制EGF、VEGF的表达,达到抗血管新生的作用,从而阻断或逆转胃癌前病变。
Objective:By observing the impact of HuaZhuoJeDuHeWei Decoction on Gastic Precancerous Lesions model rat’s general situation、gastric mucosal morphology、vascular endothelial growth factor(VEGF)、endothelial growth factors(EGF),attempt to explore:(1)the relationship between gastic precancerous lesions and the expression of VEGF、EGF;(2) effect of HuaZhuoJieDuHeWei Decoction on the expression of VEGF、EGF, and if its western medicine connotation of the treatment of gastic precancerous lesions is to inhibit angiogenesis by interferring the expression of VEGF、EGF, thereby blocking and reversing gastic precancerous lesions.and lay some experimental foundation for the treatment of gastic precancerous lesions by Chinese traditional medicine , and lay the foundation for further study of HuaZhuoJieDuHeWei Decoction.
Method:?70 SPF level healthy 6-week-old Wistar male rats, Drawn 10 with random number table as normal control group (normal group for short), The remaining 60 rats were modeled by integrated modeling method for 24 weeks. After the model been successfully built,.ratsrandomly divided the left rats into five group:model group, HuaZhuoJeDuHeWei Decoction high dose group,HuaZhuoJeDuHeWeiDecoction middle dose group,HuaZhuoJeDuHeWei Decoction low dose group, RetinoicAcid group,Each group with 9 rats. After modeling each group was treated accordingly for 16 weeks, the rats were killed in the first 40 weeks. Observe the spirit, loss of appetite, coat color and stool of rats in each group and so on, Observe pathology of gastric mucosa tissue , Measured the expression of EGF by radioimmunoassay, Immunohistochemistry was used to detect the expression of VEGF. the differences between the groups were drawn by statistical analysis, P<0.05?means the difference is statistically significant.?
Result:?(1)General condition of the rats:All the group of treatment can improve gastic precancerous lesions rats’fur color,the state of mind,the appetite,and the activity. HuaZhuoJeDuHeWei Decoction each dose group superior to improving the situation than Retinoic Acid group, but not as a normal group.(2)Observe the gastric mucosa by eyes:Gastric mucosa surface of normal group is pink, smooth, regularity. stretching is well, no hyperplastic nodules; The mucous of the model group is pale and point shape or schistose bleeds,Plica are low,rare and even disappear. stomach stretch weakened , hyperplastic nodule are visible; The mucous of the Retinoic Acid group is less pale and thin than normal group, no hyperplastic nodules;In high, middle and low-dose group, except for the general view of the stomach specimens, a few showed elastic stomach weakened, gastric mucous thinner, color pale, flattened folds or move toward disorder, we can see different levels of old bleeding points, with points, or stove-like erosion, most close to the normal group.(3)Gastric mucosa under light microscope observation: compared with model group, HuaZhuoJeDuHeWei Decoction high、middle、low-dose group and Retinoic Acid group can improve gastric mucosal lesions in rats,but the improvement of Retinoic Acid group is not as good as the HuaZhuoJeDuHeWei Decoction each dose group. The results showed that HuaZhuoJeDuHeWei Decoction has better therapeutic effection of gastric precancerous lesions in rats.(4) The expression of serum EGF: The normal group, Retinoic Acid group, low-dose group, middle-dose group, high-dose of serum EGF concentration was significantly lower than model group, the difference was statistically significant (P<0.05). Compared with model group, low-dose group, middle-dose group and high-dose group had a lower level of serum EGF, the difference was statistically significant(P<0.05).The difference between low-dose group, middle dose group, high-dose group and the Retinoic Acid group was statistically significant (P<0.05). Low、middle、high of the various groups showed no significant difference(P>0.05). It was pointed out that HuaZhuoJeDuHeWei Decoction each dose group and Retinoic Acid group can inhibit the expression of serum EGF,but HuaZhuoJeDuHeWei Decoction had better effection than Retinoic Acid, the inhabition of expression of EGF had no difference among the HuaZhuoJeDuHeWei Decoction high, middle and low-doses. HuaZhuoJeDuHeWei Decoct could significantly inhibited expression of EGF. (5) The expression of gastric mucosa VEGF : Little VEGF expressed in the normal group,while relatively strong expressed in the model group, the two groups were significantly different (P<0.05), VEGF was obviously expressed in gastic precancerous lesions . Compared with model group, high, middle and low-dose group had lower expression of VEGF, the difference was significant (P<0.05),which showed that HuaZhuoJeDuHeWei Decoct had a role of inhabiting the expression of VEGF.?There was also significant differences between Retinoic acid group and modlegroup(P<0.05). High, middle and low-dose group and the Retinoic Acid group were significantly different (P<0.05), high-dose group, middle- dose group and low- dose group showed no significant difference (P>0.05), which showed that HuazhuoJieDuHeWei Decoct could inhabit the expression of VEGF,but there was no obvious dose-response relationship.
Conclusion:(1)There is a high expression of EGF, VEGF in the gastic precancerous lesions.(2)HuaZhuoJieDuHeWeiDecoction can improve general state of rat model of gastic precancerous lesions.(3) HuaZhuoJieDuHeWei Decoction can improve impaired gastric mucosa of rat model of gastic precancerous lesions. (4) HuaZhuoJieDuHeWei Decoction can inhabit the expression of EGF、VEGF, thereby blocking and reversing gastic precancerous lesions.? The mechanism could be block and reverse gastic precancerous lesions through inhabiting the expression of VEGF、EGF, blocking the stomach ailments or reversed.
引文
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18王刚,董枚.半枝莲醇提物抗肿瘤活性的研究[J].现代中西医结合杂志,2004,13(9):1141-1143
19王建波,王庆安,董风增,等.白莪星注射液抑癌作用的实验研究[J].济宁医学院学报,2003, 26(2):12-13
20姜艳艳,石任兵,刘斌,等.半边莲中黄酮类化学成分研究[J].北京中医药大学学报,2009,32(1):59-61
21粟君,谭兴,李劲涛,等.半边莲生物碱的提取及其对胃癌细胞的抑制作用[J].西华师范大学学报(自然科学版)2007,28(4):311-313
22程仁权,程建萍,贾正红,等.全蝎治疗肿瘤的研究进展[J].中国中西结合外科杂志,2002,8(5):360
23秦晋之,闫智勇.蜈蚣的药理作用和临床应用研究进展[J].河北农业科学,2008,12(10):164-166
24 Jensen RL. Growth factor-mediated angiogenesis in themalignant progeression ofglial tumors: a review[J]. SurgNeuro,1998, 49(2): 189-195
25 AkagiM, KawaguchiM, LiuW,etal. Induction ofneuropilin-1 and vascularendothelialgrowth factorby epidermalgrowth factorin human gastric cancer cells[J]. Br JCancer, 2003, 88(5): 796-802
26 RavindranathN,Wion D, BrachetP,etal. Epidermal growth factormodulates the expression ofvascular endothelialgrowth factor in the human prostate[J]. JAndro,l 2001, 22(3): 432-443
27 SiniP, WyderL, SchnellC,et al. The antitumor and antiangiogenic activity ofvascular endothelialgrowth factor receptor inhibition is potentiated by ErbB1 blockade[ J]. Clin Cancer Res,2005, 11(12): 4521-4532
28 MaedaK,chungY,OgawaY,et al.Cancer,1996;77(5):858-863
29 Folkman J.What is the evidence that tumor are angiogenesis dependent.[J].J NatlCancer Inst,1990,82(1): 1-3
1刘启泉,杜艳茹,王志坤,等.解毒活血法治疗胃癌前病变66例临床观察[J].江苏中医药,2006,27(1):35-36
2黄明河,蔡锦莲,陈秀凤,等.萎胃1号治疗慢性萎缩性胃炎及胃癌前病变135例观察[J].世界中西医结合杂志,2007,2(4): 241 -242
3姚恩东,厉秀云,李振民.香连复胃汤治疗胃黏膜非典型增生130例[J].陕西中医,2009,30(9): 1141
4王志坤,刘红,张伟.小归芍颗粒治疗胃癌前病变119例证候疗效观察[J].河北中医,2008,40(1):28-29
5雷胜举,章红波,李刚,等.消溃异功散治疗肠上皮化生的疗效观察[J].湖北中医杂志,2007,29(1): 32-33
6蔡锦莲,李爱娣,曾兰英.萎胃散治疗慢性萎缩性胃炎临床研究[J].河南中医,2006,26(5): 28-30
7陈希源,厉秀云,李振民.中医辨证论治胃癌前病变30例[J].辽宁中医杂志,2009,36(9): 1522
8高富贵.慢性萎缩性胃炎中医辨证治疗108例[J].医学理论与实践,2004,17(8):909
9柯莹玲,单兆伟.辩证治疗慢性萎缩性胃炎癌前病变患者78例[J].上海中医药大学学报,2005,19(4):18-20
10陈良金.慢性萎缩性胃炎辩证分型与治法特点探析[J].时珍国医国药,2005,16(11):1149
11游涛,徐淑静.慢性萎缩性胃炎的中医辨治体会[J].吉林中医药,2006,26(3):29-30
12秦善文.中医辨证治疗胃癌癌前病变的临床观察[J].中国中医药现代远程教育,2008,9(6):1023-1024
13祝倩.半夏泻心汤加减治疗慢性胃炎62例[J].四川中医,2006,24(4):67
14杜秋梅.逍遥散加味治疗慢性萎缩性胃炎68例[J].中国民间疗法,2007,15(1):31
15王万卿,王岩,王晟.半夏厚朴汤加味治疗慢性萎缩性胃炎68例疗效观察[J].四川中医,2006,24(8):60
16李维柏.香砂六君子汤加减治疗慢性萎缩性胃炎临床观察[J].四川中医,2009,27(8):88
17刘连英,李继霞.温胆汤治疗慢性萎缩性胃炎临床观察[J].河南中医,2009,29(3):295
18杨扩美.乌梅丸加减治疗慢性萎缩性胃炎78例[J].陕西中医,2004,25(1):6-7
19练慧,张正立.柴胡舒肝散合四君子汤加减治疗慢性萎缩性胃炎47例[J].上海中医药杂志,2006,40(5):27-28
20卢泳,王家涛,陈日新.针药结合治疗慢性萎缩性胃炎肠化生的疗效观察[J].中国针灸,2005,25(7):457-459
21刘红.火针配合穴位注射治疗慢性萎缩性胃炎64例[J].中国中医药信息杂志,2007,14(2):53
22陈士军,徐纯超.中西医结合治疗胃癌前病变158例[J].广东医学,2006,27(4):596-597
23赵双梅,李慧臻.胃安散对慢性萎缩性胃炎大鼠HP感染及超微结构影响[J].云南中医中药杂志,2008,29(4):40-41
24陆为民,单兆伟,杨学文.仁术健胃颗粒对慢性萎缩性胃炎患者幽门螺杆菌及其cagA基因的影响[J].天津中医药,2003,20(1):26-28
25郭星,郭霞,姚希贤.慢性萎缩性胃炎胃泌素生长抑素表皮生长因子血管活性肠肤的测定及临床意义[J].世界华人消化杂志,2003,11(5):531-534
26郑世华,林寿宁,罗和生.安胃汤对大鼠慢性萎缩性胃炎胃肠激素的影响[J].中国中西医结合消化杂志,2005,13(1):33-35
27 Rhyu M G,Park W S,Melzer S J.Microsatellite instability occurs frequently in human gastric carcinoma. Oncogen,1994,9:29
28孙丽群,唐昃,段秀泉.加味左金丸对胃癌前病变大鼠胃黏膜组织细胞增殖与凋亡的影响[J].中国中西医结合消化杂志,2006,14(4):233-236
29梅武轩,曾常春.益气化瘀中药对大鼠胃癌前病变PCNA及CyclinE蛋白表达的影响[J].陕西中医,2007,28(2):247-248
30王垂杰,李岩,任明智.阻癌胃泰对胃癌前病变Bcl-2及P53基因蛋白的影响[J].中国中西医结合消化杂志,2005,13(5):281-283
2李春启,刘为纹,房殿春.实验性腺粘膜肠上皮化生模型的建立[J].解放军医学杂志,1994,19(2):131-132
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4王少明,林才经,杨春波,等.大鼠胃粘膜癌前病变实验动物模型的建立[J].药学实践杂志,2005,23(5):271-272
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8钟先锋,黄桂东.荷叶成分及功能的研究进展[J].食品与机械,2006,22(4):138-141
9 Kelly GS. Larch arabinogalactan: clinical relevance of a novel im-mue-enhancing polysaccharide[J]. AlternMed Rev, 1999, 4(2):96-103
10梅全喜,毕焕新.现代中药药理手册[M].北京:中国中医药出版社,1999:207
11薄芯,杜明莹,戍梅.沙参、砂仁、猪苓、莪术和鸡血藤对环磷酰胺毒副反应影响的实验研究[J].中国中医药科技,1997,4(3):153
12李备,刘华蓉,潘永全等.黄连总生物碱对乙醇致大鼠胃粘膜损伤的保护作用及其机制探讨[J].中国中药杂志,2006,31(1):53
13徐州,周德端,段国勋,等.中药对幽门螺杆菌抑杀作用的实验研究[J].中国医药学报,1993,8(5):25-26
14秦彩玲,刘君英,程志铭.黄连汤对实验性胃粘膜损伤[J].中国中药杂志,1994,19(7):427-428
15台卫平,罗和生.黄连素与肿瘤关系研究进展[A].国外医学肿瘤学分册,2002,29(6):425
16孟繁钦,吴宜艳,雷涛,等.茵陈的药理作用及临床应用进展[J].牡丹江医学院学报,2009,30(1):46-48
17于春艳,李薇,刘玉和,等.白花蛇舌草提取物体外抗肿瘤作用及机制研究[J].北京大学学报,2004,5(5):412-416
18王刚,董枚.半枝莲醇提物抗肿瘤活性的研究[J].现代中西医结合杂志,2004,13(9):1141-1143
19王建波,王庆安,董风增,等.白莪星注射液抑癌作用的实验研究[J].济宁医学院学报,2003, 26(2):12-13
20姜艳艳,石任兵,刘斌,等.半边莲中黄酮类化学成分研究[J].北京中医药大学学报,2009,32(1):59-61
21粟君,谭兴,李劲涛,等.半边莲生物碱的提取及其对胃癌细胞的抑制作用[J].西华师范大学学报(自然科学版)2007,28(4):311-313
22程仁权,程建萍,贾正红,等.全蝎治疗肿瘤的研究进展[J].中国中西结合外科杂志,2002,8(5):360
23秦晋之,闫智勇.蜈蚣的药理作用和临床应用研究进展[J].河北农业科学,2008,12(10):164-166
24 Jensen RL. Growth factor-mediated angiogenesis in themalignant progeression ofglial tumors: a review[J]. SurgNeuro,1998, 49(2): 189-195
25 AkagiM, KawaguchiM, LiuW,etal. Induction ofneuropilin-1 and vascularendothelialgrowth factorby epidermalgrowth factorin human gastric cancer cells[J]. Br JCancer, 2003, 88(5): 796-802
26 RavindranathN,Wion D, BrachetP,etal. Epidermal growth factormodulates the expression ofvascular endothelialgrowth factor in the human prostate[J]. JAndro,l 2001, 22(3): 432-443
27 SiniP, WyderL, SchnellC,et al. The antitumor and antiangiogenic activity ofvascular endothelialgrowth factor receptor inhibition is potentiated by ErbB1 blockade[ J]. Clin Cancer Res,2005, 11(12): 4521-4532
28 MaedaK,chungY,OgawaY,et al.Cancer,1996;77(5):858-863
29 Folkman J.What is the evidence that tumor are angiogenesis dependent.[J].J NatlCancer Inst,1990,82(1): 1-3
1刘启泉,杜艳茹,王志坤,等.解毒活血法治疗胃癌前病变66例临床观察[J].江苏中医药,2006,27(1):35-36
2黄明河,蔡锦莲,陈秀凤,等.萎胃1号治疗慢性萎缩性胃炎及胃癌前病变135例观察[J].世界中西医结合杂志,2007,2(4): 241 -242
3姚恩东,厉秀云,李振民.香连复胃汤治疗胃黏膜非典型增生130例[J].陕西中医,2009,30(9): 1141
4王志坤,刘红,张伟.小归芍颗粒治疗胃癌前病变119例证候疗效观察[J].河北中医,2008,40(1):28-29
5雷胜举,章红波,李刚,等.消溃异功散治疗肠上皮化生的疗效观察[J].湖北中医杂志,2007,29(1): 32-33
6蔡锦莲,李爱娣,曾兰英.萎胃散治疗慢性萎缩性胃炎临床研究[J].河南中医,2006,26(5): 28-30
7陈希源,厉秀云,李振民.中医辨证论治胃癌前病变30例[J].辽宁中医杂志,2009,36(9): 1522
8高富贵.慢性萎缩性胃炎中医辨证治疗108例[J].医学理论与实践,2004,17(8):909
9柯莹玲,单兆伟.辩证治疗慢性萎缩性胃炎癌前病变患者78例[J].上海中医药大学学报,2005,19(4):18-20
10陈良金.慢性萎缩性胃炎辩证分型与治法特点探析[J].时珍国医国药,2005,16(11):1149
11游涛,徐淑静.慢性萎缩性胃炎的中医辨治体会[J].吉林中医药,2006,26(3):29-30
12秦善文.中医辨证治疗胃癌癌前病变的临床观察[J].中国中医药现代远程教育,2008,9(6):1023-1024
13祝倩.半夏泻心汤加减治疗慢性胃炎62例[J].四川中医,2006,24(4):67
14杜秋梅.逍遥散加味治疗慢性萎缩性胃炎68例[J].中国民间疗法,2007,15(1):31
15王万卿,王岩,王晟.半夏厚朴汤加味治疗慢性萎缩性胃炎68例疗效观察[J].四川中医,2006,24(8):60
16李维柏.香砂六君子汤加减治疗慢性萎缩性胃炎临床观察[J].四川中医,2009,27(8):88
17刘连英,李继霞.温胆汤治疗慢性萎缩性胃炎临床观察[J].河南中医,2009,29(3):295
18杨扩美.乌梅丸加减治疗慢性萎缩性胃炎78例[J].陕西中医,2004,25(1):6-7
19练慧,张正立.柴胡舒肝散合四君子汤加减治疗慢性萎缩性胃炎47例[J].上海中医药杂志,2006,40(5):27-28
20卢泳,王家涛,陈日新.针药结合治疗慢性萎缩性胃炎肠化生的疗效观察[J].中国针灸,2005,25(7):457-459
21刘红.火针配合穴位注射治疗慢性萎缩性胃炎64例[J].中国中医药信息杂志,2007,14(2):53
22陈士军,徐纯超.中西医结合治疗胃癌前病变158例[J].广东医学,2006,27(4):596-597
23赵双梅,李慧臻.胃安散对慢性萎缩性胃炎大鼠HP感染及超微结构影响[J].云南中医中药杂志,2008,29(4):40-41
24陆为民,单兆伟,杨学文.仁术健胃颗粒对慢性萎缩性胃炎患者幽门螺杆菌及其cagA基因的影响[J].天津中医药,2003,20(1):26-28
25郭星,郭霞,姚希贤.慢性萎缩性胃炎胃泌素生长抑素表皮生长因子血管活性肠肤的测定及临床意义[J].世界华人消化杂志,2003,11(5):531-534
26郑世华,林寿宁,罗和生.安胃汤对大鼠慢性萎缩性胃炎胃肠激素的影响[J].中国中西医结合消化杂志,2005,13(1):33-35
27 Rhyu M G,Park W S,Melzer S J.Microsatellite instability occurs frequently in human gastric carcinoma. Oncogen,1994,9:29
28孙丽群,唐昃,段秀泉.加味左金丸对胃癌前病变大鼠胃黏膜组织细胞增殖与凋亡的影响[J].中国中西医结合消化杂志,2006,14(4):233-236
29梅武轩,曾常春.益气化瘀中药对大鼠胃癌前病变PCNA及CyclinE蛋白表达的影响[J].陕西中医,2007,28(2):247-248
30王垂杰,李岩,任明智.阻癌胃泰对胃癌前病变Bcl-2及P53基因蛋白的影响[J].中国中西医结合消化杂志,2005,13(5):281-283