本文選題：幽門螺桿菌 + 質子泵抑制劑��； 參考：《南京醫(yī)科大學》2014年碩士論文

【摘要】：背景：幽門螺桿菌(Helicobacter pylori, H. pylori, Hp)感染是導致胃炎、消化性潰瘍和胃癌的的主要病原菌。質子泵抑制劑(proton pump inhibitors,PPI)是有效的胃酸分泌抑制劑,是治療消化性潰瘍、上消化道出血等酸相關疾病的主要藥物。但近年來,長期PPI治療的安全性越來越受到質疑。有研究顯示長期服用PPI可以引起微量營養(yǎng)物質吸收障礙、增加腸道感染發(fā)生率,在Hp陽性個體甚至促進胃底腺息肉、萎縮性胃炎等癌前病變的發(fā)生,但最終結論仍然有爭議。目的：研究長期服用PPI對Hp感染的C57BL/6小鼠的影響,主要觀察其對胃粘膜的影響以及胃癌相關基因的改變。方法：60只C57BL/6小鼠隨機分為A、B、C、D四組,每組15只。A組為空白組,B組為Hp組,C組為PPI組,D組為Hp+P PI組。其中C和D組予含有0.05%埃索美拉唑的飼料喂養(yǎng)。飼養(yǎng)45周后,每組處死5只,57周時處死每組剩下的10只。小鼠處死后測定胃濕重和胃內pH,并將胃粘膜進行HE染色和Giemsa染色,分別觀察胃粘膜病理情況和Hp感染情況。用ELISA法測定小鼠血漿胃泌素和TFF1的水平,real-time PCR檢測小鼠胃黏膜IL-6、SOX2、CDX2、MUC5AC和TFF1基因的表達。結果：服用含有PPI飼料的C組和D組胃內pH較A、B組明顯升高,胃濕重也均較A、B組重。A、B、C和D在45周和57周處死時,均無腸上皮化生、萎縮性胃炎等癌前病變,A和C組胃粘膜正常,B組可見急慢性炎癥表現(xiàn),D組亦可見急慢性炎癥,但炎癥程度比B組重(P=0.000)。D組血漿胃泌素水平在45周和57周均最高。胃粘膜IL-6水平在B和D組均較A組升高,且57周時D組比B組明顯升高。胃粘膜SOX2的表達在B組輕度降低,在D組進一步下降,而CDX2在B組上升,在D組進一步上升。胃粘膜TFF1的水平和血漿TFF1水平表達不一致。結論：1、成功建立長期服用PPI伴Hp感染的C57BL/6小鼠模型。2、C57BL/6小鼠感染Hp14個月后可導致胃粘膜炎癥,并未產(chǎn)生萎縮性胃炎、腸上皮化生及不典型增生等癌前病變。3、PPI與Hp協(xié)同作用,使C57BL/6小鼠血漿胃泌素水平升高。4、PPI可以加重Hp誘導的炎癥反應,且呈現(xiàn)時間依賴性。5、Hp感染并應用PPI后,C57BL/6小鼠胃粘膜相關抑癌基因表達降低,促癌基因表達上升。
[Abstract]:Background: Helicobacter pylori (HP) infection is a major cause of gastritis, peptic ulcer and gastric cancer. Proton pump inhibitor (proton pump inhibitors) is an effective inhibitor of gastric acid secretion, and is the main drug for the treatment of peptic ulcer, upper gastrointestinal bleeding and other acid-related diseases. However, in recent years, the safety of long-term PPI treatment is increasingly questioned. Some studies have shown that long-term use of PPI can cause micronutrient absorption disorders, increase the incidence of intestinal infection in HP positive individuals and even promote the occurrence of precancerous lesions such as fundus polyps and atrophic gastritis, but the final conclusion is still controversial. Aim: to study the effect of long-term PPI on Hp-infected C57BL / 6 mice, and to observe the effect of PPI on gastric mucosa and the changes of gastric cancer related genes. Methods Sixty C57BL / 6 mice were randomly divided into four groups: group A (n = 15), group B (n = 15), group C (HP), group C (P Pi), group D (P Pi). Groups C and D were fed with a diet containing 0.05% esomeprazole. After 45 weeks of feeding, 5 rats were killed in each group and the remaining 10 rats in each group were killed at 57 weeks. The gastric wet weight and intragastric pH were measured after the mice were killed. The gastric mucosa was stained with HE and Giemsa. The pathological changes of gastric mucosa and HP infection were observed. The levels of plasma gastrin and TFF1 in mice were determined by Elisa and real-time PCR was used to detect the expression of MUC5AC and TFF1 genes in mouse gastric mucosa. Results: the intragastric pH of group C and D fed with PPI diet was significantly higher than that of group A B, and the wet weight of stomach was also higher than that of group A, B, C and D at 45 and 57 weeks after death, there was no intestinal metaplasia. Acute and chronic inflammation was also seen in group D, but the degree of inflammation was higher in group D than that in group B (P < 0.05). Plasma gastrin levels in group D were higher than those in group B (n = 45) and group C (n = 57). The level of IL-6 in gastric mucosa in group B and D was higher than that in group A, and at 57 weeks, the level of IL-6 in group D was significantly higher than that in group B. The expression of SOX2 in gastric mucosa decreased slightly in group B and decreased further in group D, while CDX2 increased in group B and increased in group D. The expression of TFF1 in gastric mucosa was not consistent with that in plasma. ConclusionThe mouse model of long-term PPI with HP infection in C57BL / 6 mice was successfully established. The infection of Hp14 months in C57BL / 6 mice with PPI could lead to gastric mucosal inflammation, without atrophic gastritis, intestinal metaplasia, atypical hyperplasia and other precancerous lesions, such as PPI and HP. The increase of plasma gastrin level in C57BL / 6 mice. 4 PPI could aggravate the inflammation induced by HP, and the expression of tumor suppressor genes in gastric mucosa of C57BL / 6 mice was decreased and the expression of oncogene was increased after PPI application.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R573

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