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L-161982對(duì)實(shí)驗(yàn)性自身免疫性神經(jīng)炎大鼠趨化因子表達(dá)的影響

發(fā)布時(shí)間:2018-05-29 07:21

  本文選題:大鼠 + 實(shí)驗(yàn)性自身免疫性神經(jīng)炎; 參考:《山東大學(xué)》2014年碩士論文


【摘要】:研究目的: 吉蘭-巴雷綜合征(Guillain-Barre syndrome, GBS)是以周圍神經(jīng)髓鞘脫失和小血管炎性細(xì)胞浸潤(rùn)為病理特點(diǎn)的自身免疫性周圍神經(jīng)病,以肢體對(duì)稱性弛緩性癱瘓為主要臨床特征。實(shí)驗(yàn)性自身免疫性神經(jīng)炎(experimental autoimmune neuritis,EAN)是國(guó)際公認(rèn)的研究GBS的動(dòng)物模型,是T輔助細(xì)胞1和T輔助細(xì)胞17(Thl/Th17)介導(dǎo)的自身免疫性疾病,以周圍神經(jīng)脫髓鞘和大量炎性細(xì)胞浸潤(rùn)為主要病理特點(diǎn)。這些浸潤(rùn)的炎性細(xì)胞主要包括單核巨噬細(xì)胞、淋巴細(xì)胞以及粒細(xì)胞,促炎性細(xì)胞因子如IFN-γ、TNF-α、NO及趨化因子MCP-1、MIP-1等在其發(fā)病中起關(guān)鍵作用。 近年來(lái)研究認(rèn)為前列腺素E2(Prostaglandin E2)是一種免疫激活劑,可能通過(guò)作用于EP4受體影響Thl和Th17這兩個(gè)細(xì)胞亞群的分化來(lái)參與自身免疫性疾病的免疫炎癥過(guò)程,由此我們推測(cè)PGE2-EP4受體拮抗劑對(duì)EAN具有治療作用。在我們的前期研究中發(fā)現(xiàn),應(yīng)用PGE2-EP4拮抗劑L-161982干預(yù)EAN大鼠,可降低其坐骨神經(jīng)中促炎性細(xì)胞因子IL-17及IFN-y的表達(dá);谮吇蜃釉贕BS/EAN中的重要作用,本實(shí)驗(yàn)觀察了PGE2-EP4拮抗劑L-161982對(duì)EAN大鼠趨化因子CXCL-12和MCP-1表達(dá)的影響。 實(shí)驗(yàn)方法: 1.用周圍神經(jīng)鞘磷脂(BPM)免疫Lewis大鼠,制備EAN模型。 2.隨機(jī)將21只EAN大鼠分為3組,治療A組、治療B組和對(duì)照組。兩個(gè)治療組均以劑量為5mg/kg的PGE2-EP4受體拮抗劑L-161982腹腔注射治療。治療A組于免疫階段(免疫前1天至免疫后第8天)每日行L-161982處理,治療B組于發(fā)病階段(免疫后第5天至第14天)每日行L-161982處理。對(duì)照組在整個(gè)實(shí)驗(yàn)階段每日給予相同體積的L-161982溶媒DMSO腹腔注射。 3.免疫后每日觀察EAN大鼠的臨床評(píng)分。于免疫后第15天處死EAN大鼠,取其坐骨神經(jīng),用免疫組化法檢測(cè)坐骨神經(jīng)中趨化因子CXCL-12及MCP-1的表達(dá)水平。 4.應(yīng)用SPSS18.0軟件對(duì)資料進(jìn)行統(tǒng)計(jì)分析,數(shù)據(jù)以x±s表示。 實(shí)驗(yàn)結(jié)果: 1.與對(duì)照組相比,不同階段處理的兩個(gè)治療組均能延遲EAN的發(fā)病時(shí)間(P0.05),降低其高峰期臨床評(píng)分(P0.05),減少坐骨神經(jīng)中CXCL-12和MCP-1的表達(dá)(P0.05)。 2.兩個(gè)治療組間發(fā)病時(shí)間、高峰期臨床評(píng)分以及趨化因子表達(dá)的比較,均可見顯著差異(P0.05)。 結(jié)論: 1.應(yīng)用L-161982治療可明顯延遲EAN大鼠的發(fā)病時(shí)間,降低其高峰期臨床評(píng)分,改善EAN大鼠的臨床癥狀,說(shuō)明其對(duì)周圍神經(jīng)自身免疫性疾病有治療作用。 2.應(yīng)用L-161982治療可抑制EAN大鼠坐骨神經(jīng)中趨化因子CXCL-12及MCP-1的表達(dá),提示PGE2-EP4受體拮抗劑L-161982可通過(guò)抑制巨噬細(xì)胞和T細(xì)胞的遷移活化,減少CXCL-12和MCP-1的產(chǎn)生,從而抑制免疫炎癥反應(yīng),這可能是L-161982的抗炎機(jī)制之一。 3.與發(fā)病階段相比,免疫階段應(yīng)用PGE2-EP4受體拮抗劑L-161982更能顯著延遲EAN大鼠的發(fā)病時(shí)間,降低其高峰期評(píng)分,減少坐骨神經(jīng)中趨化因子CXCL-12和MCP-1的表達(dá)。因此,免疫階段使用L-161982治療效果更顯著。
[Abstract]:Objectives of the study: Guillain-Barre syndromeGuillain-Barre syndrome (GBSs) is an autoimmune peripheral neuropathy characterized by peripheral nerve demyelination and small vascular inflammatory cell infiltration. The main clinical feature is limb symmetric flaccid paralysis. Experimental autoimmune neuritis (EAN) is an internationally recognized animal model for the study of GBS. It is an autoimmune disease mediated by T helper cell 1 and T helper cell 17 Thl / Th17. The main pathological features were demyelination of peripheral nerve and infiltration of inflammatory cells. These infiltrating inflammatory cells mainly include mononuclear macrophages, lymphocytes and granulocytes, pro-inflammatory cytokines such as IFN- 緯 -TNF- 偽 no and chemokine MCP-1 / MIP-1, which play a key role in its pathogenesis. In recent years, it has been suggested that prostaglandin E2(Prostaglandin E2 (PGE) is an immune activator, which may be involved in the immune inflammation of autoimmune diseases by affecting the differentiation of Thl and Th17 subsets by acting on EP4 receptors. Therefore, we speculate that PGE2-EP4 receptor antagonist has therapeutic effect on EAN. In our previous study, it was found that PGE2-EP4 antagonist L-161982 could reduce the expression of pro-inflammatory cytokines IL-17 and IFN-y in sciatic nerve of EAN rats. Based on the important role of chemokines in GBS/EAN, the effects of PGE2-EP4 antagonist L-161982 on the expression of chemokines CXCL-12 and MCP-1 in EAN rats were studied. Experimental methods: 1. Lewis rats were immunized with peripheral nerve sphingolipid (BPM) to establish EAN model. 2. Twenty-one EAN rats were randomly divided into three groups: group A, group B and control group. Both groups were treated by intraperitoneal injection of PGE2-EP4 receptor antagonist L-161982 (5mg/kg). Group A was treated daily with L-161982 during the immune phase (from 1 day before immunization to 8 days after immunization) and group B was treated daily with L-161982 at the onset stage (from the 5th to the 14th day after immunization). The control group was given intraperitoneal injection of L-16 1982 solvent DMSO daily during the whole phase of the experiment. 3. The clinical scores of EAN rats were observed daily after immunization. On the 15th day after immunization, EAN rats were killed and their sciatic nerves were removed. The expression of chemokine CXCL-12 and MCP-1 in sciatic nerve was detected by immunohistochemical method. 4. The data were analyzed by SPSS18.0 software, and the data were expressed as x 鹵s. Experimental results: 1. Compared with the control group, the two treatment groups at different stages could delay the onset of EAN, decrease the peak clinical score and decrease the expression of CXCL-12 and MCP-1 in sciatic nerve. 2. There were significant differences in onset time, peak clinical score and chemokine expression between the two groups (P 0.05). Conclusion: 1. L-161982 treatment can significantly delay the onset of EAN rats, reduce its peak clinical score, improve the clinical symptoms of EAN rats, indicating that it has therapeutic effect on peripheral nerve autoimmune diseases. 2. L-161982 treatment could inhibit the expression of chemokine CXCL-12 and MCP-1 in sciatic nerve of EAN rats, suggesting that PGE2-EP4 receptor antagonist L-161982 could inhibit the production of CXCL-12 and MCP-1 by inhibiting the migration and activation of macrophages and T cells. This may be one of the anti-inflammatory mechanisms of L-161982. 3. PGE2-EP4 receptor antagonist L-161982 significantly delayed the onset of EAN rats, decreased its peak score, and reduced the expression of chemokines CXCL-12 and MCP-1 in sciatic nerve. Therefore, the effect of L-161982 was more significant in the immune phase.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R744.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 吳強(qiáng)強(qiáng);孫黎飛;;格林巴利綜合征相關(guān)研究近況[J];實(shí)用醫(yī)藥雜志;2010年07期

2 袁錦楣,李海峰;格林-巴利綜合征研究的最新進(jìn)展[J];中國(guó)實(shí)用內(nèi)科雜志;2000年01期

3 魯曉麗;譚曉冬;;前列腺素E2-EP4受體拮抗劑對(duì)大鼠實(shí)驗(yàn)性自身免疫性神經(jīng)炎的作用[J];山東大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2013年03期

4 張敬各;陳海英;秦瑾;叢斌;李巧霞;賈嫻嫻;馬春玲;于峰;;PGE_2受體EP2和EP4調(diào)節(jié)CIA小鼠脾B細(xì)胞表面分子和細(xì)胞因子表達(dá)[J];中國(guó)病理生理雜志;2011年03期

5 周勁松;;大劑量免疫球蛋白聯(lián)合甲潑尼龍治療急性格林巴利綜合征的臨床療效[J];中國(guó)現(xiàn)代藥物應(yīng)用;2012年02期

6 王坤亮;朱家攀;;大劑量丙種球蛋白聯(lián)合甲基強(qiáng)的松龍治療急性格林巴利綜合征36例療效觀察[J];中國(guó)傷殘醫(yī)學(xué);2014年04期

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