參七消痞顆粒治療氨水復合多因素致大鼠慢性萎縮性胃炎的實驗研究
發(fā)布時間：2019-05-22 06:51
【摘要】：目的：基于氨水建立大鼠慢性萎縮性胃炎模型的基本模型,探索復合多因素建立大鼠慢性萎縮性胃炎模型的新方法,為治療慢性萎縮性胃炎的藥物研究奠定基礎；對“參七消痞顆�！边M行治療CAG的臨床前研究,以期獲得具有獨立知識產(chǎn)權(quán)的治療慢性萎縮性胃炎的中藥新藥。 方法： 1.氨水復合多刺激因素致大鼠萎縮性胃炎：結(jié)合脫氧膽酸鈉、酒精、水楊酸鈉及高鹽飲食,并輔以饑飽失調(diào)、冷熱失常等因素刺激,進行建立氨水復合多刺激因素致大鼠萎縮性胃炎的模型研究。日常觀察大鼠行為,毛色,進食飲水量,體重變化趨勢等,分別于造模第12周、20周、24周處死動物,觀察胃竇部組織病理改變；著重觀察20周、24周胃液分泌情況,血液中反應萎縮程度、胃腸激素水平、癌變相關因子的情況,胃組織病理改變情況。 2.“參七消痞顆�！睂Π彼畯秃隙啻碳ひ蛩刂麓笫笪s性胃炎的治療作用及機制研究：依據(jù)實驗第1部分摸索出的方法建立大鼠CAG模型,把模型組大鼠體重均勻的分為如下幾組：模型組、SQ高劑量組、SQ中劑量組、SQ低劑量組、葉酸組、摩羅丹組,日常飲用新鮮氨水,并灌胃相應藥物,日常觀察大鼠行為表現(xiàn),體重變化,分別于給藥8周及12周取材,做胃分泌功能檢測,做反映萎縮程度、胃腸激素、癌前病變相關細胞因子的血液分析,及胃粘膜組織病理學檢測。 結(jié)果： 1.氨水復合多刺激因素致大鼠萎縮性胃炎的模型研究：①體重變化：與空白對照組相比,模型組動物體重增長緩慢,模型組動物體重顯著降低(P0.05)。②胃分泌功能：與空白對照組相比,模型組動物胃酸度降低,有顯著差異(P0.05)。③組織學改變：造模第12周時模型組大鼠胃粘膜細胞排列散亂,粘膜固有層有充血,粘膜肌層增厚,腺體結(jié)構(gòu)紊亂并萎縮,胃小凹加深,至第24周模型組動物病理改變加重,有杯狀細胞出現(xiàn)：從造模12周開始,模型組腺體減少,與空白組相比有顯著差異(P0.05)；粘膜肌層厚度(L2)均值高于空白組,有顯著差異(P0.05)；L1/L2均值低于空白組,有顯著差異(P0.05),該趨勢一直保持到24周；PCNA陽性染色率顯著高于空白組。 2.“參七消痞顆�！睂Π彼畯秃隙啻碳ひ蛩刂麓笫笪s性胃炎的治療作用及機制研究：給藥8周、12周后,與空白組相比,模型組雄性大鼠體重均值低于空白組,存在顯著差異(P0.05)；給藥8周、12周后,與空白組相比,模型組胃液酸度低于空白組,有顯著差異(P0.05)；給藥8周后,模型組血液中胃蛋白酶原Ⅰ(PGI)水平顯著低于空白組(P0.05),模型組生長激素(GH)水平顯著低于空白組(P0.05)；給藥12周后,模型組血清PGE2水平顯著低于空白組(P0.05)；粘膜腺體數(shù)較空白組少、粘膜肌層變厚存在顯著差異(P0.05),以上結(jié)果符合模型特征,模型有效。①體重變化：給藥8-12周,與模型組相比,各給藥組大鼠平均體重差異不顯著,陽性藥葉酸組和SQ低劑量組有明顯高于模型組的趨勢。②胃分泌功能檢測：給藥8周后,與模型組相比,各給藥組胃液酸度均高于模型組,其中“參七消痞顆�！备邉┝拷MPH低于模型組(P0.05)；與模型組相比,SQ高劑量組、SQ中劑量組、陽性藥葉酸組胃液分泌量有顯著差異(P0.05)。給藥12周后,各給藥組胃液酸度均高于模型組,其中“參七消痞顆粒”高劑量組、中劑量組酸度顯著高于模型組(P0.05)。給藥12周后,與模型組相比,SQ中劑量組胃游離粘液值高于模型組,差異顯著(P0.05)。③血液分析：給藥期間,與模型組相比,給藥8周后,各給藥組的血清胃蛋白酶原Ⅰ(PGI)均值均高于模型組,其中SQ中劑量組和SQ低劑量組胃蛋白酶原Ⅰ(PGI)均值高于模型組(P0.05),有統(tǒng)計學意義；“參七消痞顆�！备邉┝拷M、中劑量組生長激素(GH)水平高于模型組,有顯著差異(P0.05)；④胃粘膜組織病理學檢測：給藥12周,SQ高劑量組、中劑量組、陽性藥摩羅丹組胃粘膜肌層厚度均值小于模型組,差異顯著(P0.05)；“參七消痞顆�！备邉┝拷M、中劑量組、低劑量組、陽性藥摩羅丹組L1/L2值均高于模型組,差異顯著(P0.05)。給藥8周及12周后,與模型組大鼠相比,各給藥組胃粘膜腺體數(shù)較模型組顯著增加(P0.05)。給藥8周后,與模型組相比,“參七消痞顆�！敝�、低劑量組、陽性藥葉酸組PCNA染色率顯著低于模型組(P0.05)。給藥12周后,與模型組大鼠相比,各給藥組PCNA染色率顯著低于模型組(P0.05)。 結(jié)論： 1.采用上述與CAG致病誘因相關的多種刺激因素建立大鼠CAG模型,12周時模型動物的一般癥狀和組織學病理表現(xiàn)與臨床CAG患者吻合,20周及24周后模型動物的胃液分泌、胃粘膜屏障、血液檢測、病理變化等數(shù)據(jù)顯示模型較穩(wěn)定,造模成功,本項研究為相關藥物的研究奠定并豐富了模型基礎。 2.“參七消痞顆�！睂Π彼畯秃隙啻碳ひ蛩刂麓笫笪s性胃炎的治療作用及機制研究：綜合“參七消痞顆�！睂AG模型大鼠的影響觀察結(jié)果分析,我們可以看出“參七消痞顆粒”對氨水復合多因素致慢性萎縮性胃炎模型大鼠粘膜營養(yǎng)因子分泌有改善作用,刺激胃酸分泌,起到一定修復胃粘膜,改善胃功能及改善胃粘膜萎縮的作用,降低模型PCNA染色率,減小癌變幾率。
[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.
【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R285.6;R-332
本文編號：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.
【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R285.6;R-332
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