【作者】 齐晶晶；

【导师】 王贤斌；

【作者基本信息】 湖北中医学院 ， 中医内科学， 2009， 硕士

【摘要】 目的:研究和中消溃汤对乙酸溃疡模型大鼠胃粘膜的保护作用,探讨其发挥保护作用促进溃疡愈合的作用机制,为中医药治疗胃溃疡提供实验依据。方法:在质量为200-250g的70只健康成年雄性大鼠中随机抽取10只作为正常空白对照组,余下60只均用乙酸烧灼法造模:在腺胃部腹面胃体与幽门窦交界处的浆膜下近肌层处注射100%乙酸液体30μl,形成直径约3mm白色小丘,造模后第4天在造模60只大鼠中随机抽取10只大鼠剖腹取胃观察溃疡形成情况,判断造模效果,以成功率>80%时,认为造模成功。余下50只大鼠随机分为5组,加上先前正常空白对照组,共6组:正常空白对照组、模型组、和中消溃汤大剂量组、和中消溃汤中剂量组、和中消溃汤小剂量组、丽珠得乐组,造模第5天用大剂量（25.2g/Kg*d）,中剂量（12.6g/Kg*d）,小剂量（6.3g/Kg*d）和中消溃汤、丽珠得乐（0.36g/Kg*d）分别给用药组大鼠灌胃,正常空白对照组、模型组给以生理盐水。持续灌胃16天,1次/天。16天后处死大鼠,断头取血,测量血浆ET含量;剖腹取胃,取溃疡组织切片、分别作HE染色及PAS染色以观察灌胃后各模型组大鼠的溃疡愈合情况,用显微镜测微尺定量测量胃再生粘膜厚度;取溃疡边缘胃组织匀浆后测NO、MDA、SOD含量,取腺胃组织匀浆后测EGF、6-Keto-PGF₁a含量,比较各组间差异,用SPSS统计软件处理分析数据。结果:1.对乙酸溃疡模型大鼠胃再生粘膜厚度的影响:和中消溃汤大剂量组、中剂量组、小剂量组和丽珠得乐组大鼠再生粘膜厚度均明显高于模型组（P<0.05～0.01）;和中消溃汤大剂量组明显高于丽珠得乐组（P<0.05）,丽珠得乐组与和中消溃汤中剂量组之间无显著性差异（P>0.05）,和中消溃汤在增加再生粘膜厚度方面,各剂量组之间存在量效关系。2、对乙酸溃疡模型大鼠胃组织一氧化氮（NO）及超氧化物歧化酶（SOD）含量的影响:和中消溃汤大剂量组、中剂量组、小剂量组大鼠胃组织NO及SOD的含量明显高于模型组与丽珠得乐组（P<0.05或P<0.01）,丽珠得乐组与模型组之间上述指标无显著性差异（P>0.05）,和中消溃汤大剂量组与正常组之间无显著性差异（P>0.05）,和中消溃汤在增加大鼠胃组织NO及SOD方面各剂量组之间存在量效关系。3.对乙酸溃疡型大鼠血浆内皮素（ET）和胃组织丙二醛（MDA）含量的影响:和中消溃汤大、中、小剂量组大鼠血浆ET和胃组织MDA含量明显低于模型组与丽珠得乐组（P<0.01或P<0.05）,丽珠得乐组与模型组之间上述指标无显著性差异（P>0.05）,和中消溃汤大剂量组与正常组之间无显著性差异（P>0.05）,和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。4.对乙酸溃疡型大鼠胃组织表皮生长因子（EGF）和6-酮-前列腺素F₁a（6-Keto-PGF₁a）含量的影响:和中消溃汤大、中、小剂量组,丽珠得乐组大鼠胃组织表皮生长因子（EGF）和6-酮-前列腺素F₁a（6-Keto-PGF₁a）含量明显高于于模型组（P<0.01）,丽珠得乐组表皮生长因子（EGF）含量略高于和中消溃汤大剂量组,差别无显著性意义（P>0.05）。但丽珠得乐组6-酮-前列腺素F₁a（6-Keto-PGF₁a）含量明显高于和中消溃汤大剂量组（P<0.05）,和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。结论:和中消溃汤能显著增加乙酸溃疡模型大鼠胃再生粘膜厚度以促进溃疡愈合,其作用优于丽珠得乐,呈剂量依赖性关系。其作用机理可能与其增加胃组织EGF、SOD、NO、6-Keto-PGF₁a含量和减少MDA、血浆ET含量有关,增强胃粘膜的保护作用是和中消溃汤治疗胃溃疡的机制之一。此实验说明了和中消溃汤组方用药的合理性和科学性,对于指导临床治疗胃溃疡中医用药以及开发新药等,都具有一定的参考价值。更多还原

【Abstract】 Objective:To investigate the protective effect of Hezhongxiaokui decoction on gastric mucosa of rats with ulcer induced byAcetic Acid.To study its therapeutic effect as well as the possible mechanism.And to provide a clinical rationale for treatment of gastric ulcer.Methods:10 of 70 male healthy adult rats from quality,range 200—250g,were choosed to form the normal control group at random. The others were all induced chronic gastric ulcer by Acetic Acid,（inject 30μl 100%Acetic Acid at the Subserosa of juncture of the ventral aspect corpus gastricum of stomachus glandularis and gastric antrum to form a white nodule with approxinate diameter of 3mm ）.At the 4th day after modiing 10 rats were choosed to evaluate whether the modle was successful.If success rates was greater than 80%,successful modle was seen established.The left 50 rats were devided into 5 groups at random:Model group、high dose group of Hezhongxiaokui decoction（25.2g/Kg*d）、medium dose group of Hezhongxiaokui decoction（12.6g/Kg*d）、low dose group of Hezhongxiaokui decoction（6.3g/Kg*d）、Lizhu Dele group（0.36g/Kg*d）. Rats of Hezhong Xiaokui decoction group and Lizhu Dele group were intragastric administrated Hezhong Xiaokui Physic liquors and Lizhu Dele Physic liquors respectively,one time per day,totally 16 days.The others were intragastric administratednormal saline. 16 days later,All the rats were executed to collect blood to detect the content of Plasma ET,and rats’ s belly were cut open and removed the stomach to slice the scar of ulcer tissue.After HE dyeing and PAS dyeing separately we observed the healing condition of the ulce,r and measured the thickness of regenerative mucosa,Meanwhile, we detect the content of NO、MDA、SOD、EGF、6-Keto-PGF,a of stomach tissue.At last we compared the difference of interclass and analyzed data by SPSS statistics software.Results:1.The determination the thickness of theregeneratice mucosa on chronic gastric ulcer rats has showed that compared with model group, the thickness of gastric mucosa increased significantly in each dose of Hezhong Xiaokui group and Lizhu Dele group（P<0.05-0.01）, High dose group of Hezhongxiaokui decoction had muchthicker regeneratice mucosa than Lizhu Dele group,and there was remarkable difference between the high dose group and the LizhuDelegroup （P<0.05）.and there was no significant difference between the high dose group and the normal control group（P>0.05）.On increasing the thickness of the regeneratice mucosa on chronic gastric ulcer rats there’s a dose-dependent effect in the result. 2.The determination of the content of SOD and NO has showed that the content of SOD and NO of each dose group of Hezhongxiaokui decoction is much higher than that of LizhuDele and model group,and there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group（P<0.05-0.01）.There was no significant difference between normal group and high dose group as well as the model group and LizhuDele group（P>0.05）.On increasing the content of SOD and NO,there’s a dose-dependent effect in the result.3.The determination of the content of ET and MDA has showed that the content of ET and MDA of each dose group of Hezhongxiaokui decoction is much lower than that of LizhuDele and model group, there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group（R<0.05-0.01）.There was no significant difference between normal control group and high dose group as well as the model group and LizhuDele group（P>0.05）. On decreasing the content of SOD and NO?there’s a dose-dependent effect in the result.4.The determination of the content of EGF and 6-Keto-PGF₁a has showed that the content of EGF and 6-Keto-PGF₁a of each dose group of Hezhongxiaokui decoction and LizhuDele group is much higher than that of model group,and the content of 6-Keto-PGF₁a of LizhuDele group is much higher than that of each dose group of Hezhongxiaokui decoction（P<0.01）.while the EGF a little higher（P>0.05）.On increasing the content of SOD and NO,there’ s a dose-dependent effect in the result.Conclusions:Hezhongxiaokui decoction can pronote the growth of the regeneratice mucosa on rats to accelerate the ulcer healing up and the effect was better thanLizhu Dele.the effect in the result was dose-dependent.It might be due to improvement of the the level of SOD、NO、EGF、6-Keto-PGF₁a and its decrease of the ET and MDA levels.Enhancing the protective effect on gastric mucosa was one of possible mechanisms on Hezhongxiaokui decoction treating gastric ulcer.The study provide a reference data for understanding the mechanism of this therapeutic method.Meanwhile,it is valuable for guiding the clinical practice in treating gastric ulcer and development of new medication.更多还原