本文選題：潰瘍性結腸炎 + 乳汁球微粒表皮生長因子8��； 參考：《川北醫(yī)學院》2016年碩士論文

【摘要】：研究背景:潰瘍性結腸炎(ulcerative colitis,UC)是一種非特異性慢性腸道炎癥性疾病,該病主要累及直腸和結腸粘膜及粘膜下層。臨床主要表現(xiàn)為腹痛、腹瀉、解粘液膿血便,大多為慢性病程。UC的的病因及其發(fā)病機制尚未完全闡明。目前認為遺傳、環(huán)境以及機體自身免疫因素在其發(fā)病過程中起了重要作用。乳汁球微粒表皮生長因子8(milk fat globule-epidermal growth factor 8,MFG-E8)是一種分泌型多效糖蛋白,可在多種細胞中表達。MFG-E8在腸道炎癥調節(jié)和腸道粘膜的修復中起到重要作用。有研究表明在疾病的急性狀態(tài)下MFG-E8的表達是顯著減少的,在停止給予葡聚糖硫酸酯鈉(dextran sulfate sodium,DSS)喂養(yǎng)后的再生狀態(tài)下MFG-E8是升高的,最后當疾病被廢除后MFG-E8回復正常水平。三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)誘導的結腸炎中發(fā)現(xiàn)MFG-E8表達的改變與上述相同。也有研究表明用rMFG-E8處理DDS誘導的小鼠結腸炎后觀察到其在抑制腸道炎癥是有效的。這些研究說明了MFG-E8在腸道炎癥調節(jié)中起到重要作用。此外,有研究表明在DSS誘導的小鼠結腸炎恢復期,給予小鼠外源的重組MFG-E8能加快腸粘膜損傷的修復,MFG-E8在腸道受損粘膜組織再生修復過程中發(fā)揮著重要作用。核轉錄因子-κB(Nuclear Factor kappa B,NF-κB)是調控基因轉錄的重要因子。參與了許多免疫炎癥反應的基因轉錄調控,細胞凋亡和腫瘤細胞轉移等病理生理過程基因調控,在腸道炎癥調節(jié)起到重要作用,在免疫細胞通信機制和細胞因子產(chǎn)生的失調的uc發(fā)病機制中構成其主要調節(jié)。有在哺乳動物中nf-κb家族由5個成員組成:rel、rela(p65)、relb、p50和p52,其中p65具有顯著的促炎特性研究表明在uc患者腸道在uc病人的粘膜巨噬細胞和上皮細胞中是活化狀態(tài)。研究發(fā)現(xiàn)nf-κbp65在uc患者腸道粘膜上皮、隱窩上皮和固有層單核細胞中高度表達,且細胞核的表達明顯高于細胞質。nf-κb在uc中呈過度激活狀態(tài),并導致細胞因子及粘附分子等過度和持續(xù)表達,從而放大炎癥反應。研究報道m(xù)fg-e8可以通過干預αvβ3信號通路減輕腸道粘膜炎癥。外源性重組mfg-e8治療小鼠急性腸炎中的腸粘膜損傷,主要通過限制核因子nf-κb的活性進而使促炎介質如tnf-α、il-1等表達下調。本研究通過檢測mfg-e8、nf-κbp65在正常及uc患者腸粘膜的表達情況,并分析其相關關系以及與疾病活動性的關系,探討其在uc的臨床意義。目的:1.研究mfg-e8、nf-κbp65在正常人和不同程度uc患者腸粘膜的表達情況。2.探討二者之間相互關系及二者與uc疾病活動性關系和發(fā)病過程的作用以及其臨床意義。方法:收集川北醫(yī)學院附屬醫(yī)院明確診斷的uc患者39例和正常人對照組19例。用免疫組化檢測uc患者和正常對照組腸粘膜組織mfg-e8、nf-κbp65的表達水平。uc患者的臨床嚴重程度按改良的truelove和witts嚴重程度分度,疾病活動度按改良的mayo評分系統(tǒng)計算疾病活動指數(shù)(dai,0-12分),根據(jù)baron標準進行內鏡分級,按照truelove-richards標準進行病理組織學分級。結果:MFG-E8、NF-κBp65主要存在于人腸粘膜腸上皮細胞、隱窩上皮。在UC組MFG-E8表達明顯低于對照組,相反NF-κBp65表達明顯高于對照組。兩者在UC和正常粘膜中的表達均存在統(tǒng)計學差異(P0.05)。MFG-E8在UC患者活動期和緩解期腸粘膜中的陽性表達率分別為6.3%、26.1%,NF-κBp65在UC患者活動期和緩解期腸粘膜中的陽性表達率分別為93.8%、69.6%,并且隨疾病嚴重程度增加MFG-E8陽性數(shù)逐漸減少,輕度組高于重度組(P0.05),隨內鏡、病理組織學分級增加,MFG-E8陽性數(shù)逐漸減少。而NF-κBp65陽性數(shù)是隨疾病嚴重程度逐漸增加,重度高于輕度(P0.05),隨內鏡、病理組織學分級增加,UC患者結腸粘膜中NF-κBp65陽性數(shù)增加,III級顯著高于I級(P0.05)。在39例UC患者中MFG-E8、NF-κBp65陽性例數(shù)和陰性例數(shù)Pearson相關分析顯MFG-E8與NF-κBp65表達呈負相關(r=-1.000 P0.01)。結論:1.MFG-E8、NF-κBp65表達水平與UC疾病嚴重程度和病情分期密切相關。2.MFG-E8、NF-κBp65的表達水平與內鏡分級和病理學分級密切相關。3.MFG-E8與NF-κBp65呈負相關,提示MFG-E8和NF-κBp65可能參與UC疾病的發(fā)生、發(fā)展,聯(lián)合檢查其表達水平有助于判斷病情的炎癥程度。
[Abstract]:Background: ulcerative colitis (UC) is a nonspecific chronic intestinal inflammatory disease. The disease mainly involves the mucosa and submucosa of the rectum and colon. The main clinical manifestations are abdominal pain, diarrhea, and mucus purulent blood stool. Most of the causes and pathogenesis of.UC in the chronic course of disease have not been fully elucidated. Currently, it is believed that the pathogenesis and pathogenesis of the disease have not been fully elucidated. Heredity, environment and autoimmune factors play an important role in its pathogenesis. The milk ball microparticle epidermal growth factor 8 (milk fat globule-epidermal growth factor 8, MFG-E8) is a kind of secretory multi effect glycoprotein, which can express.MFG-E8 in many kinds of cells and play an important role in the regulation of intestinal inflammation and the repair of intestinal mucosa. Use. Studies have shown that the expression of MFG-E8 is significantly reduced in the acute condition of the disease, and MFG-E8 is elevated under the regenerative state of dextran sulfate sodium, DSS, and MFG-E8 reverting to normal levels after the disease is abolished. Three nitrobenzene sulfonic acid (trinitrobenzene sulfonic acid, TNBS) The changes in MFG-E8 expression are the same as those found in colitis guided. Some studies have shown that rMFG-E8 is effective in inhibiting intestinal inflammation after DDS induced colitis in mice. These studies show that MFG-E8 plays an important role in the regulation of intestinal inflammation. In addition, studies have shown the recovery of colitis induced by DSS in mice. The exogenous recombinant MFG-E8 can accelerate the repair of intestinal mucosal damage, and MFG-E8 plays an important role in the regeneration and repair of intestinal mucosa damaged mucosa. Nuclear factor kappa B (Nuclear Factor kappa B, NF- kappa B) is an important factor regulating gene transcription. Gene regulation of pathophysiological processes, such as death and tumor cell metastasis, plays an important role in the regulation of intestinal inflammation and constitutes its main regulation in the mechanism of immune cell communication and the dysregulation of cytokine production in UC. In mammals, the nf- kappa B family consists of 5 members: rel, rela (p65), RelB, P50 and p52, of which p65 has a display. The study showed that the intestinal tract was activated in the mucous macrophages and epithelial cells of UC patients in UC patients. The study found that nf- kappa bp65 was highly expressed in the intestinal mucosa, recess epithelium and lamina propria of UC patients, and the expression of the nucleus was significantly higher than that of the cytoplasm of.Nf- kappa B in UC. It is reported that mfg-e8 can reduce intestinal mucosal inflammation by interfering with alpha v beta 3 signaling pathway. Exogenous recombinant mfg-e8 is used to treat intestinal mucosal injury in acute enteritis in mice, mainly by limiting the activity of nuclear factor nf- kappa B to make proinflammatory mediators such as tnf- In this study, the expression of mfg-e8, nf- kappa bp65 in the intestinal mucosa of normal and UC patients was detected, and the relationship between the expression of nf- kappa bp65 and the activity of the disease was analyzed and the clinical significance of nf- kappa in UC was explored. Objective: 1. to study the expression of nf- kappa bp65 in the intestinal mucosa of normal people and other UC patients. The relationship between the two and the UC disease activity and the pathogenesis of the disease and its clinical significance. Methods: 39 cases of UC patients and 19 normal controls in Affiliated Hospital of Chuanbei Medical College were collected, and 19 cases of UC patients and normal controls were used to detect the expression level of nf- kappa bp65 in.Uc patients. The clinical severity was graded according to the improved truelove and witts severity, and the disease activity was calculated according to the improved Mayo score system (Dai, 0-12). The endoscopic classification was conducted according to the Baron standard, and the histopathological classification was carried out according to the truelove-richards standard. MFG-E8, NF- kappa Bp65 mainly existed in the intestinal mucosa intestinal epithelium. The expression of MFG-E8 in the UC group was significantly lower than that in the control group, but the expression of NF- kappa Bp65 was significantly higher than that in the control group. The expression of the two in the UC and normal mucosa was statistically different (P0.05) the positive expression rate of.MFG-E8 in the active and remission period of UC patients was 6.3%, 26.1%, and NF- kappa Bp65 in the active period of UC patients. The positive expression rate in the intestinal mucosa was 93.8%, 69.6%, and the positive number of MFG-E8 decreased with the severity of the disease, and the mild group was higher than the severe group (P0.05). With the endoscopy, the histopathological classification was increased and the positive number of MFG-E8 decreased gradually. The positive number of NF- kappa Bp65 was gradually increased with the severity of the disease, and the severity was higher than that of the mild (P0.05). With the increase of endoscopic and histopathological grading, the positive number of NF- kappa Bp65 in the colon mucosa of UC patients was increased, and the III level was significantly higher than that of I (P0.05). In 39 patients with UC, MFG-E8, the number of NF- kappa Bp65 positive and negative case number Pearson correlation analysis showed negative correlation between the expression of MFG-E8 and the expression of nuclear kappa. The severity of the disease is closely related to the staging of the disease. The expression level of NF- kappa Bp65 is closely related to the endoscopic classification and pathological classification..3.MFG-E8 is negatively correlated with NF- kappa Bp65. It suggests that MFG-E8 and NF- kappa Bp65 may be involved in the occurrence of UC diseases. The development of the Bp65 and NF- kappa Bp65 may help to determine the degree of inflammation of the disease.
【學位授予單位】：川北醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R574.62

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