本文選題：四甲基吡嗪　切入點(diǎn)：眼內(nèi)炎癥　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:葡萄膜炎在臨床上是常見的多發(fā)致盲性眼部疾病,主要由感染和自身免疫異常所致,發(fā)病病程長(zhǎng),難治易復(fù)發(fā)。長(zhǎng)期反復(fù)持續(xù)的炎癥可導(dǎo)致患者的視力產(chǎn)生不可逆且永久性的損害。目前發(fā)現(xiàn)自身免疫是葡萄膜炎發(fā)生的最主要致病病因,臨床治療的藥物及方案一直是眼科領(lǐng)域里的重要研究課題。目的:本實(shí)驗(yàn)探討了四甲基吡嗪(Tetramethylpyrazine,TMP)對(duì)實(shí)驗(yàn)性自身免疫性葡萄膜炎(Experimental autoimmune uveitis,EAU)動(dòng)物模型的抗炎作用及其潛在的機(jī)制。方法:在B10RIII小鼠腿部及尾基部皮下注射IRBP肽誘導(dǎo)EAU動(dòng)物模型。預(yù)防階段的處理:對(duì)B10RIII小鼠分別使用TMP或vehicle腹腔注射3天后開始皮下注射IRBP制作EAU模型,再分別每天連續(xù)使用TMP或vehicle腹腔注射14天。效應(yīng)階段的處理:對(duì)B10RIII小鼠皮下注射IRBP制作EAU模型后第8天開始分別每天連續(xù)使用TMP或vehicle腹腔注射直至第14天。觀察每組小鼠前房炎癥再分別進(jìn)行臨床評(píng)分和組織學(xué)評(píng)分,評(píng)估EAU小鼠眼內(nèi)炎癥的嚴(yán)重情況,檢測(cè)小鼠視網(wǎng)膜功能狀態(tài)。提取每組小鼠視網(wǎng)膜的m RNA樣本,并使用real-time PCR分別檢查炎性因子IL-6、TNF-α、IL-1β、MCP-1,抗炎因子IL-10以及T細(xì)胞相關(guān)的因子IFN-γ和IL-17的表達(dá)變化。采用Western blotting檢測(cè)p-STAT3和p-STAT4的蛋白表達(dá)水平。結(jié)果:在預(yù)防和效應(yīng)這兩個(gè)階段中,TMP顯著減輕EAU小鼠的前房及后房炎癥,抑制IL-6、TNF-α、IL-1β、MCP-1、IFN-γ和IL-17的m RNA表達(dá)水平,并提高IL-10的m RNA水平。同時(shí),經(jīng)TMP治療后的EAU小鼠ERG中a波和b波振幅明顯升高,且p-STAT3和p-STAT4的蛋白表達(dá)水平明顯下調(diào)。結(jié)論:全身應(yīng)用TMP可明顯減輕EAU小鼠的眼內(nèi)炎癥和視網(wǎng)膜功能障礙。這種抗炎作用與抑制STAT3和STAT4通路的活化有關(guān)。因此TMP可能成為治療葡萄膜炎的新方案。
[Abstract]:Background: uveitis is a common ocular disease with multiple blindness in clinic. It is mainly caused by infection and autoimmune abnormality, and the course of the disease is long. Persistent inflammation can lead to irreversible and permanent visual impairment. Autoimmunity is now found to be the leading cause of uveitis. The drugs and protocols of clinical treatment have been an important research topic in ophthalmology. Objective: to investigate the anti-inflammatory effect and potential of Tetramethylpyrazine tetramethylpyrazine (TMP) on experimental experimental autoimmune uveitis (EAU) animal model. Methods: EAU animal model was induced by subcutaneous injection of IRBP peptide into the legs and base of tail of B10RIII mice. During the prevention stage, B10RIII mice were injected TMP or vehicle intraperitoneally for 3 days to make EAU model. The treatment of the effect stage: on the 8th day after the B10RIII mice were subcutaneously injected with IRBP to make EAU model, TMP or vehicle were injected intraperitoneally until the 14th day, respectively. The clinical and histological scores of anterior chamber inflammation were evaluated in each group. To evaluate the severity of intraocular inflammation in EAU mice, to detect the retinal function of mice, and to extract m RNA samples from the retina of each group. Real-time PCR was used to detect the expression of IL-6TNF- 偽 -IL-1 尾, anti-inflammatory factor IL-10 and T-cell related factors IFN- 緯 and IL-17, respectively. Western blotting was used to detect the expression of p-STAT3 and p-STAT4. Results: in the two stages of prevention and effect, the expression of p-STAT3 and p-STAT4 was detected. TMP significantly alleviated anterior chamber and posterior chamber inflammation in EAU mice. It inhibited the expression of m RNA in MCP-1tIFN- 緯 and IL-17, and increased the m RNA level of IL-10 in IL-6 TNF- 偽 -IL-1 尾. At the same time, the amplitudes of a and b waves in ERG of EAU mice treated with TMP were significantly increased. The protein expression of p-STAT3 and p-STAT4 was significantly down-regulated. Conclusion: systemic application of TMP can significantly reduce the intraocular inflammation and retinal dysfunction in EAU mice. This anti-inflammatory effect is related to the inhibition of the activation of STAT3 and STAT4 pathways. It can be a new treatment for uveitis.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R773.9

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