【作者】 崔建从；

【导师】 李佃贵；

【作者基本信息】 河北医科大学 ， 中西医结合临床， 2010， 硕士

【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。更多还原

【Abstract】 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.更多还原