参七消痞颗粒治疗氨水复合多因素致大鼠慢性萎缩性胃炎的实验研究
发布时间：2019-05-22 06:51
【摘要】：目的：基于氨水建立大鼠慢性萎缩性胃炎模型的基本模型,探索复合多因素建立大鼠慢性萎缩性胃炎模型的新方法,为治疗慢性萎缩性胃炎的药物研究奠定基础；对“参七消痞颗粒”进行治疗CAG的临床前研究,以期获得具有独立知识产权的治疗慢性萎缩性胃炎的中药新药。 方法： 1.氨水复合多刺激因素致大鼠萎缩性胃炎：结合脱氧胆酸钠、酒精、水杨酸钠及高盐饮食,并辅以饥饱失调、冷热失常等因素刺激,进行建立氨水复合多刺激因素致大鼠萎缩性胃炎的模型研究。日常观察大鼠行为,毛色,进食饮水量,体重变化趋势等,分别于造模第12周、20周、24周处死动物,观察胃窦部组织病理改变；着重观察20周、24周胃液分泌情况,血液中反应萎缩程度、胃肠激素水平、癌变相关因子的情况,胃组织病理改变情况。 2.“参七消痞颗粒”对氨水复合多刺激因素致大鼠萎缩性胃炎的治疗作用及机制研究：依据实验第1部分摸索出的方法建立大鼠CAG模型,把模型组大鼠体重均匀的分为如下几组：模型组、SQ高剂量组、SQ中剂量组、SQ低剂量组、叶酸组、摩罗丹组,日常饮用新鲜氨水,并灌胃相应药物,日常观察大鼠行为表现,体重变化,分别于给药8周及12周取材,做胃分泌功能检测,做反映萎缩程度、胃肠激素、癌前病变相关细胞因子的血液分析,及胃粘膜组织病理学检测。 结果： 1.氨水复合多刺激因素致大鼠萎缩性胃炎的模型研究：①体重变化：与空白对照组相比,模型组动物体重增长缓慢,模型组动物体重显著降低(P0.05)。②胃分泌功能：与空白对照组相比,模型组动物胃酸度降低,有显著差异(P0.05)。③组织学改变：造模第12周时模型组大鼠胃粘膜细胞排列散乱,粘膜固有层有充血,粘膜肌层增厚,腺体结构紊乱并萎缩,胃小凹加深,至第24周模型组动物病理改变加重,有杯状细胞出现：从造模12周开始,模型组腺体减少,与空白组相比有显著差异(P0.05)；粘膜肌层厚度(L2)均值高于空白组,有显著差异(P0.05)；L1/L2均值低于空白组,有显著差异(P0.05),该趋势一直保持到24周；PCNA阳性染色率显著高于空白组。 2.“参七消痞颗粒”对氨水复合多刺激因素致大鼠萎缩性胃炎的治疗作用及机制研究：给药8周、12周后,与空白组相比,模型组雄性大鼠体重均值低于空白组,存在显著差异(P0.05)；给药8周、12周后,与空白组相比,模型组胃液酸度低于空白组,有显著差异(P0.05)；给药8周后,模型组血液中胃蛋白酶原Ⅰ(PGI)水平显著低于空白组(P0.05),模型组生长激素(GH)水平显著低于空白组(P0.05)；给药12周后,模型组血清PGE2水平显著低于空白组(P0.05)；粘膜腺体数较空白组少、粘膜肌层变厚存在显著差异(P0.05),以上结果符合模型特征,模型有效。①体重变化：给药8-12周,与模型组相比,各给药组大鼠平均体重差异不显著,阳性药叶酸组和SQ低剂量组有明显高于模型组的趋势。②胃分泌功能检测：给药8周后,与模型组相比,各给药组胃液酸度均高于模型组,其中“参七消痞颗粒”高剂量组PH低于模型组(P0.05)；与模型组相比,SQ高剂量组、SQ中剂量组、阳性药叶酸组胃液分泌量有显著差异(P0.05)。给药12周后,各给药组胃液酸度均高于模型组,其中“参七消痞颗粒”高剂量组、中剂量组酸度显著高于模型组(P0.05)。给药12周后,与模型组相比,SQ中剂量组胃游离粘液值高于模型组,差异显著(P0.05)。③血液分析：给药期间,与模型组相比,给药8周后,各给药组的血清胃蛋白酶原Ⅰ(PGI)均值均高于模型组,其中SQ中剂量组和SQ低剂量组胃蛋白酶原Ⅰ(PGI)均值高于模型组(P0.05),有统计学意义；“参七消痞颗粒”高剂量组、中剂量组生长激素(GH)水平高于模型组,有显著差异(P0.05)；④胃粘膜组织病理学检测：给药12周,SQ高剂量组、中剂量组、阳性药摩罗丹组胃粘膜肌层厚度均值小于模型组,差异显著(P0.05)；“参七消痞颗粒”高剂量组、中剂量组、低剂量组、阳性药摩罗丹组L1/L2值均高于模型组,差异显著(P0.05)。给药8周及12周后,与模型组大鼠相比,各给药组胃粘膜腺体数较模型组显著增加(P0.05)。给药8周后,与模型组相比,“参七消痞颗粒”中、低剂量组、阳性药叶酸组PCNA染色率显著低于模型组(P0.05)。给药12周后,与模型组大鼠相比,各给药组PCNA染色率显著低于模型组(P0.05)。 结论： 1.采用上述与CAG致病诱因相关的多种刺激因素建立大鼠CAG模型,12周时模型动物的一般症状和组织学病理表现与临床CAG患者吻合,20周及24周后模型动物的胃液分泌、胃粘膜屏障、血液检测、病理变化等数据显示模型较稳定,造模成功,本项研究为相关药物的研究奠定并丰富了模型基础。 2.“参七消痞颗粒”对氨水复合多刺激因素致大鼠萎缩性胃炎的治疗作用及机制研究：综合“参七消痞颗粒”对CAG模型大鼠的影响观察结果分析,我们可以看出“参七消痞颗粒”对氨水复合多因素致慢性萎缩性胃炎模型大鼠粘膜营养因子分泌有改善作用,刺激胃酸分泌,起到一定修复胃粘膜,改善胃功能及改善胃粘膜萎缩的作用,降低模型PCNA染色率,减小癌变几率。
[Abstract]:Objective: To establish the basic model of the model of chronic atrophic gastritis in rats based on the ammonia water, and to explore the new method of establishing the model of chronic atrophic gastritis in rats by using the compound multi-factor, and to lay the foundation for the study of the drug of chronic atrophic gastritis, and to study the "Shenqi Xiaoyao Granules" for the treatment of chronic atrophic gastritis. In order to obtain a traditional Chinese medicine for treating chronic atrophic gastritis with independent intellectual property. square Method:1. The compound multi-stimulation of aqueous ammonia induced atrophic gastritis in rats: combined with sodium deoxycholate, alcohol, sodium salicylate and high-salt diet, and supplemented with the factors such as hunger and food, cold and cold, and so on. The rats were sacrificed at 12 weeks,20 weeks and 24 weeks, and the pathological changes of the stomach and stomach were observed. The results of the study were to observe the secretion of gastric juice at 20 weeks and 24 weeks, the degree of atrophy of the reaction in the blood, and the gastrointestinal shock. The pathological changes of the gastric tissue in the case of the level of the level of the cancer and the related factors of the canceration 2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water: the model of CAG was established according to the method of the first part of the experiment, and the weight of the model group was divided into the following groups: model group, SQ high dose group, S Q middle dose group, SQ low dose group, folic acid group and Danone group, fresh ammonia water was drunk daily, and the corresponding drugs were given intragastric administration. The behavior and body weight of the rats were observed daily, and the materials were collected for 8 weeks and 12 weeks respectively, and the function of gastric secretion was detected, and the degree of atrophy was reflected. Blood analysis of cytokines, gastrointestinal hormones, pre-cancerous lesion-related cytokines, and gastric mucosal tissue pathology The results were as follows:1. The model of the rats with atrophic gastritis induced by the compound multi-stimulation of ammonia water: the body weight change: the body weight of the model group was slow in the model group compared with the blank control group, and the body weight of the model group was significant. Decrease in gastric acid secretion in the model group compared with the blank control group (P0.05). The pathological changes of the gastric mucosa in the model group at the 12th week of the model were scattered, the lamina propria of the mucosa was hyperemia, the muscular layer of the mucous membrane was thickened, the structure of the gland was disordered and the gastric depression was increased, and the pathological changes of the animals in the model group were added to the model group at the 24th week. The expression of L1/ L2 was higher than that of blank group (P0.05). The mean value of L1/ L2 was lower than that of blank group, and there was significant difference (P0.05). The potential remained until 24 weeks; PCNA positive staining The color rate was significantly higher than that of the blank group.2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water:8 weeks and 12 weeks after administration, the mean body weight of the model group was lower than that of the blank group, and there was a significant difference (P0.05); and the administration was 8 weeks. After 12 weeks, the acidity of gastric juice in the model group was lower than that of the blank group (P0.05). The level of pepsinogen I (PGI) in the blood of the model group was significantly lower than that in the blank group after 8 weeks of administration (P0.05). The level of the growth hormone (GH) in the model group was significantly lower than that of the blank group (P0.05). .05) After 12 weeks of administration, the level of PGE2 in the model group was significantly lower than that in the blank group (P0.05); the number of mucosal glands was lower than that in the blank group, and there was a significant difference in the thickening of the mucous layer of the mucous membrane (P0.05), and the above results According to the model characteristics, the model is effective. The body weight change:8-12 weeks for administration, the average body weight difference of the rats in each treatment group is not significant compared with the model group, and the positive drug folic acid group and the SQ low-dose group There was a significantly higher trend in the model group than in the model group. After 8 weeks of administration, the acidity of the gastric juice of each treatment group was higher than that of the model group (P0.05). Compared with the model group, the SQ of the high-"Shenqi Xiaoyao Granules" high-dose group was lower than that of the model group (P0.05). The amount of gastric juice in the high-dose group and the SQ group was the same as that in the positive-drug-folic acid group. Significant difference (P0.05). After 12 weeks of administration, the acidity of the gastric juice in each treatment group was higher than that of the model group. In the high-"Shenqi Xiaoyao Granules" group, the acidity of the middle-dose group was significantly higher. In the model group (P0.05), after 12 weeks of administration, the gastric free mucus value in the SQ group was higher than that of the model group compared with the model group. The difference was significant (P0.05). The mean value of the serum pepsinogen I (PGI) in each treatment group was higher than that of the model group (P0.05). The mean value of the serum pepsinogen I (PGI) in each treatment group was higher than that of the model group (P0.05). (05) There was a statistical significance; in the "high dose group", the level of growth hormone (GH) in the middle dose group was higher than that of the model group, and there was a significant difference (P0.05); and the histopathological examination of the gastric mucosa:12 weeks, the SQ high dose group, the middle dose group, the positive drug group, and the gastric mucosa of the Danone group. The mean value of the thickness of the myometrium was less than that of the model group, and the difference was significant (P0.05); in the high-"Shenqi Xiaoyao Granules" high-dose group, the middle-dose group, the low-dose group and the positive drug-group-group L1/ L2 value were higher than that of the model group, The difference was significant (P0.05). Compared with the model group rats, the number of gastric mucosal glands in each treatment group was higher than that of the model group after 8 and 12 weeks of administration. Significant increase (P0.05). After 8 weeks of administration, the staining rate of PCNA was significantly lower in the "Shenqi Xiaoyao Granules", in the lower dose group and in the positive drug folate group than in the model group. In the model group (P0.05), the PCNA staining rate was significantly lower in each treated group than in the model group after 12 weeks of administration. on the model Conclusion:1. The CAG model of rats was established by the above-mentioned factors related to the cause of CAG. The general symptoms and the pathological findings of the model animals at 12 weeks were consistent with the clinical CAG patients, and the model animals after 20 and 24 weeks. The data of gastric juice secretion, gastric mucosal barrier, blood test and pathological changes showed that the model was stable and the model was successful. The study was related to this study. The study of the medicine has laid and enriched the model base.2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water: the comprehensive "Shenqi Xiaoyao Granules" The results of the observation on the effect of the model of CAG model on the rats in CAG model can be seen in this paper. We can see the effect of Shenqi Xiao-xiao granule on the secretion of mucosal nutritional factors in rats with chronic atrophic gastritis induced by multi-factor of ammonia water, stimulate the secretion of gastric acid, and play a role in repairing the gastric mucosa, improving the function of the stomach and improving the gastric mucosa. The effect of atrophy.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285.6;R-332
本文编号：2482760
[Abstract]:Objective: To establish the basic model of the model of chronic atrophic gastritis in rats based on the ammonia water, and to explore the new method of establishing the model of chronic atrophic gastritis in rats by using the compound multi-factor, and to lay the foundation for the study of the drug of chronic atrophic gastritis, and to study the "Shenqi Xiaoyao Granules" for the treatment of chronic atrophic gastritis. In order to obtain a traditional Chinese medicine for treating chronic atrophic gastritis with independent intellectual property. square Method:1. The compound multi-stimulation of aqueous ammonia induced atrophic gastritis in rats: combined with sodium deoxycholate, alcohol, sodium salicylate and high-salt diet, and supplemented with the factors such as hunger and food, cold and cold, and so on. The rats were sacrificed at 12 weeks,20 weeks and 24 weeks, and the pathological changes of the stomach and stomach were observed. The results of the study were to observe the secretion of gastric juice at 20 weeks and 24 weeks, the degree of atrophy of the reaction in the blood, and the gastrointestinal shock. The pathological changes of the gastric tissue in the case of the level of the level of the cancer and the related factors of the canceration 2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water: the model of CAG was established according to the method of the first part of the experiment, and the weight of the model group was divided into the following groups: model group, SQ high dose group, S Q middle dose group, SQ low dose group, folic acid group and Danone group, fresh ammonia water was drunk daily, and the corresponding drugs were given intragastric administration. The behavior and body weight of the rats were observed daily, and the materials were collected for 8 weeks and 12 weeks respectively, and the function of gastric secretion was detected, and the degree of atrophy was reflected. Blood analysis of cytokines, gastrointestinal hormones, pre-cancerous lesion-related cytokines, and gastric mucosal tissue pathology The results were as follows:1. The model of the rats with atrophic gastritis induced by the compound multi-stimulation of ammonia water: the body weight change: the body weight of the model group was slow in the model group compared with the blank control group, and the body weight of the model group was significant. Decrease in gastric acid secretion in the model group compared with the blank control group (P0.05). The pathological changes of the gastric mucosa in the model group at the 12th week of the model were scattered, the lamina propria of the mucosa was hyperemia, the muscular layer of the mucous membrane was thickened, the structure of the gland was disordered and the gastric depression was increased, and the pathological changes of the animals in the model group were added to the model group at the 24th week. The expression of L1/ L2 was higher than that of blank group (P0.05). The mean value of L1/ L2 was lower than that of blank group, and there was significant difference (P0.05). The potential remained until 24 weeks; PCNA positive staining The color rate was significantly higher than that of the blank group.2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water:8 weeks and 12 weeks after administration, the mean body weight of the model group was lower than that of the blank group, and there was a significant difference (P0.05); and the administration was 8 weeks. After 12 weeks, the acidity of gastric juice in the model group was lower than that of the blank group (P0.05). The level of pepsinogen I (PGI) in the blood of the model group was significantly lower than that in the blank group after 8 weeks of administration (P0.05). The level of the growth hormone (GH) in the model group was significantly lower than that of the blank group (P0.05). .05) After 12 weeks of administration, the level of PGE2 in the model group was significantly lower than that in the blank group (P0.05); the number of mucosal glands was lower than that in the blank group, and there was a significant difference in the thickening of the mucous layer of the mucous membrane (P0.05), and the above results According to the model characteristics, the model is effective. The body weight change:8-12 weeks for administration, the average body weight difference of the rats in each treatment group is not significant compared with the model group, and the positive drug folic acid group and the SQ low-dose group There was a significantly higher trend in the model group than in the model group. After 8 weeks of administration, the acidity of the gastric juice of each treatment group was higher than that of the model group (P0.05). Compared with the model group, the SQ of the high-"Shenqi Xiaoyao Granules" high-dose group was lower than that of the model group (P0.05). The amount of gastric juice in the high-dose group and the SQ group was the same as that in the positive-drug-folic acid group. Significant difference (P0.05). After 12 weeks of administration, the acidity of the gastric juice in each treatment group was higher than that of the model group. In the high-"Shenqi Xiaoyao Granules" group, the acidity of the middle-dose group was significantly higher. In the model group (P0.05), after 12 weeks of administration, the gastric free mucus value in the SQ group was higher than that of the model group compared with the model group. The difference was significant (P0.05). The mean value of the serum pepsinogen I (PGI) in each treatment group was higher than that of the model group (P0.05). The mean value of the serum pepsinogen I (PGI) in each treatment group was higher than that of the model group (P0.05). (05) There was a statistical significance; in the "high dose group", the level of growth hormone (GH) in the middle dose group was higher than that of the model group, and there was a significant difference (P0.05); and the histopathological examination of the gastric mucosa:12 weeks, the SQ high dose group, the middle dose group, the positive drug group, and the gastric mucosa of the Danone group. The mean value of the thickness of the myometrium was less than that of the model group, and the difference was significant (P0.05); in the high-"Shenqi Xiaoyao Granules" high-dose group, the middle-dose group, the low-dose group and the positive drug-group-group L1/ L2 value were higher than that of the model group, The difference was significant (P0.05). Compared with the model group rats, the number of gastric mucosal glands in each treatment group was higher than that of the model group after 8 and 12 weeks of administration. Significant increase (P0.05). After 8 weeks of administration, the staining rate of PCNA was significantly lower in the "Shenqi Xiaoyao Granules", in the lower dose group and in the positive drug folate group than in the model group. In the model group (P0.05), the PCNA staining rate was significantly lower in each treated group than in the model group after 12 weeks of administration. on the model Conclusion:1. The CAG model of rats was established by the above-mentioned factors related to the cause of CAG. The general symptoms and the pathological findings of the model animals at 12 weeks were consistent with the clinical CAG patients, and the model animals after 20 and 24 weeks. The data of gastric juice secretion, gastric mucosal barrier, blood test and pathological changes showed that the model was stable and the model was successful. The study was related to this study. The study of the medicine has laid and enriched the model base.2. The effect and mechanism of the "Shenqi Xiaoyao Granules" on the treatment of atrophic gastritis induced by the compound multi-stimulation factor of ammonia water: the comprehensive "Shenqi Xiaoyao Granules" The results of the observation on the effect of the model of CAG model on the rats in CAG model can be seen in this paper. We can see the effect of Shenqi Xiao-xiao granule on the secretion of mucosal nutritional factors in rats with chronic atrophic gastritis induced by multi-factor of ammonia water, stimulate the secretion of gastric acid, and play a role in repairing the gastric mucosa, improving the function of the stomach and improving the gastric mucosa. The effect of atrophy.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R285.6;R-332
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