本文選題：原發(fā)性膽汁性膽管炎 + 抗線粒體抗體　； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：研究背景及目的:原發(fā)性膽汁性膽管炎(primary biliary cholangitis,PBC)是一種進(jìn)行性的自身免疫性肝病,主要引起患者肝內(nèi)膽管損傷,引發(fā)膽汁淤積性癥狀,導(dǎo)致肝纖維化,最終導(dǎo)致肝衰竭。PBC的發(fā)病機(jī)制尚不明確,PBC的發(fā)病機(jī)制尚不明確,并無特異性的臨床表現(xiàn),早期診斷率并不是很高,而PBC晚期的患者只能進(jìn)行肝移植治療。因此,對(duì)高危人群進(jìn)行定期篩查,提高PBC的早期診斷率,對(duì)PBC患者的治療以及改善患者的預(yù)后均有很大的幫助�？咕�粒體抗體M2亞型(AMA-M2)是臨床上診斷PBC的特異性生物學(xué)指標(biāo),臨床上主要通過血清途徑進(jìn)行AMA-M2的檢測,但是,血清檢測途徑具有很多自身缺陷,如有創(chuàng)傷、感染風(fēng)險(xiǎn)、不夠方便等,因此,AMA-M2的無創(chuàng)檢測方法具有很大的研究前景。本實(shí)驗(yàn)?zāi)康脑谟诶米灾鞲倪M(jìn)的方法檢測唾液中AMA-M2的水平及唾液中炎癥因子的表達(dá),評(píng)估唾液中AMA-M2在該疾病中的診斷價(jià)值,以及PBC患者口腔免疫環(huán)境的變化,進(jìn)而對(duì)PBC的早期診斷提供新的方法。研究方法本研究收集了 PBC患者、口腔扁平苔蘚(oral lichen planus,OLP)患者和健康成年人(health controls,HC)的血清和唾液樣本共151例。利用酶聯(lián)免疫吸附法(Enzyme-linked Immunosorbent assay,ELISA)檢測三組血清和唾液樣本中AMA-M2的表達(dá)水平,用液相芯片檢測三組唾液和血清樣本中炎癥性細(xì)胞因子的表達(dá)水平,通過t檢驗(yàn),單因素方差分析比較分析各組AMA-M2表達(dá)水平及細(xì)胞因子表達(dá)水平之間的差異,還利用Pearson相關(guān)性分析的方法分析了 AMA-M2及細(xì)胞因子表達(dá)水平在唾液和血液之間的聯(lián)系。同時(shí),我們還檢測了 PBC組和HC組血清中堿性磷酸酶(Alkaline phosphatase,ALP)、谷氨酰轉(zhuǎn)肽酶(Gamma-glutamyl transpeptidase,GGT)的水平。研究結(jié)果:研究發(fā)現(xiàn)唾液的AMA-M2水平只能在血清AMA-M2表達(dá)陽性的PBC患者中測得,而在血清AMA-M2表達(dá)陰性的PBC患者、OLP組、HC組中,唾液AMA-M2的表達(dá)低于檢測下限。同時(shí),我們發(fā)現(xiàn)在血清AMA-M2表達(dá)陽性的PBC患者中,血清和唾液中AMA-M2表達(dá)水平存在明顯的正相關(guān)性。另一方面,在PBC組和OLP組唾液中IL-6、IFN-γ,TNF-α,IL-17A表達(dá)水平均比HC組明顯升高,而IL-10的變化不明顯,并且OLP組唾液中炎癥性細(xì)胞因子表達(dá)水平比PBC組也有明顯升高。結(jié)論:唾液具有無創(chuàng)、便捷的優(yōu)勢(shì),且能夠一定程度上反映血液中相關(guān)成分的表達(dá)情況。唾液AMA-M2在PBC診斷中有較高的靈敏度和特異度,在PBC的早期診斷和高危群體的篩查中具有較高的應(yīng)用價(jià)值,也為PBC的早期診斷提供了 一個(gè)新的方向。同時(shí),我們發(fā)現(xiàn)PBC患者口腔內(nèi)存在Th1/Th2失衡,Th17相關(guān)炎性細(xì)胞.因子的表達(dá)升高,患者發(fā)病過程中可能存在著出現(xiàn)口腔炎癥性疾病風(fēng)險(xiǎn),這為臨床上PBC的治療提供了更多的思路與理論基礎(chǔ)。
[Abstract]:Background and objective: primary biliary cholangitis is a progressive autoimmune liver disease. The pathogenesis of liver failure. PBC is not clear, there is no specific clinical manifestation, the early diagnosis rate is not very high, but the late PBC patients can only be treated with liver transplantation. Therefore, regular screening of high-risk groups to improve the rate of early diagnosis of PBC, the treatment of PBC patients and improve the prognosis of patients have a great help. AMA-M2) is a specific biological index for clinical diagnosis of PBC. In clinic, AMA-M2 is mainly detected by serum pathway. However, serum detection pathway has many defects, such as trauma and risk of infection. Therefore, the non-invasive detection method of AMA-M2 has great research prospect. The purpose of this study was to detect the level of AMA-M2 in saliva and the expression of inflammatory factors in saliva, to evaluate the diagnostic value of AMA-M2 in saliva and the changes of oral immune environment in patients with PBC. It provides a new method for early diagnosis of PBC. Methods Serum and saliva samples of PBC patients, oral lichen planus lichen patients and healthy adults were collected. Enzyme linked immunosorbent assay (Elisa) was used to detect the expression of AMA-M2 in serum and saliva samples of three groups, and the expression of inflammatory cytokines in saliva and serum samples of three groups was detected by liquid-phase microarray, and the expression of inflammatory cytokines in saliva and serum samples was detected by t test. Univariate ANOVA was used to compare and analyze the differences of AMA-M2 expression and cytokine expression in each group. The relationship between saliva and blood of AMA-M2 and cytokine expression was also analyzed by Pearson correlation analysis. At the same time, we also detected the levels of alkaline phosphatase (ALP) and glutamyl transpeptidase (GGTs) in the serum of PBC and HC groups. Results: the results showed that the AMA-M2 level of saliva could only be detected in PBC patients with positive serum AMA-M2 expression, but the expression of AMA-M2 in saliva was lower than the lower detection limit in PBC patients with negative AMA-M2 expression. At the same time, we found that there was a positive correlation between AMA-M2 expression in serum and saliva in PBC patients with positive AMA-M2 expression. On the other hand, the level of IL-6 IFN- 緯 TNF- 偽 IL-17A in saliva of PBC group and OLP group was significantly higher than that of HC group, but the change of IL-10 was not obvious, and the expression of inflammatory cytokines in saliva of OLP group was significantly higher than that of PBC group. Conclusion: saliva has the advantages of noninvasive and convenient, and can reflect the expression of related components in blood to some extent. Salivary AMA-M2 has high sensitivity and specificity in the diagnosis of PBC. It has a high value in the early diagnosis of PBC and screening of high-risk population. It also provides a new direction for the early diagnosis of PBC. At the same time, we found that Th1/Th2 imbalance and Th17-related inflammatory cells were found in the oral cavity of PBC patients. The increased expression of factors may lead to the risk of oral inflammatory diseases in the pathogenesis of patients, which provides more ideas and theoretical basis for the clinical treatment of PBC.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575.7

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本文編號(hào)：1990370