發(fā)布時(shí)間：2018-04-13 20:03

  本文選題：Toll樣受體- + B淋巴細(xì)胞刺激因子�。� 參考：《免疫學(xué)雜志》2017年09期

【摘要】：目的研究Toll樣受體-4(Toll-like receptors-4,TLR-4)與B淋巴細(xì)胞刺激因子(B lymphocyte stimulator,BLys)在系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus,SLE)轉(zhuǎn)基因小鼠模型中的作用及可能機(jī)制,為SLE的治療提供新靶點(diǎn)。方法選擇SPF級(jí)EB病毒膜抗原BLLF1轉(zhuǎn)基因雌性小鼠共30只,隨機(jī)分成空白對(duì)照組、BLys阻斷劑組和TLR-4阻斷劑組各10只,選擇SPF級(jí)野生型小鼠為野生對(duì)照組。BLys阻斷劑組應(yīng)用抗BR3單克隆抗體500 mg/d,腹腔注射連續(xù)10 d,TLR-4阻斷劑組應(yīng)用抗人TLR-4抗體250 mg/d,腹腔注射連續(xù)10 d,野生對(duì)照組和空白對(duì)照組腹腔注射等量生理鹽水。繼續(xù)喂養(yǎng)10 d后無(wú)菌取尾靜脈血,RT-PCR法檢測(cè)TLR-4 m RNA水平,ELISA法檢測(cè)白細(xì)胞介素-6(interleukin-6,IL-6)、IL-17、腫瘤壞死因子-α(tumor necrosis factor alpha,TNF-α)和IL-2水平,金標(biāo)免疫斑點(diǎn)法檢測(cè)抗ds DNA抗體滴度,常規(guī)生化法檢測(cè)補(bǔ)體C3(complement 3)、血沉(erythrocyte sedimentation rate,ESR)和C反應(yīng)蛋白(C-reaction protein,CRP)水平,對(duì)小鼠腎臟進(jìn)行HE和Masson染色。結(jié)果野生對(duì)照組和BLys阻斷劑組,空白對(duì)照組和TLR-4阻斷劑組外周血中單個(gè)核細(xì)胞(PBMC)的BLys無(wú)統(tǒng)計(jì)學(xué)差異(P0.05);與野生對(duì)照組和BLys阻斷劑組比,空白對(duì)照組和TLR-4阻斷劑組PBMC的BLys明顯增高(P0.05)。提示EB病毒膜抗原BLLF1轉(zhuǎn)基因小鼠為SLE模型,BLys阻斷劑可阻斷PBMC的BLys的表達(dá)。野生對(duì)照組和空白對(duì)照組干預(yù)前后的TLR-4 m RNA、IL-6、IL-17、TNF-α、IL-2、抗ds DNA抗體、C3、ESR和CRP表達(dá)無(wú)明顯差異(P0.05);空白對(duì)照組、BLys阻斷劑組和TLR-4阻斷劑組干預(yù)前外周血TLR-4 m RNA、IL-6、IL-17、TNF-α、抗ds DNA抗體、C3、ESR和CRP表達(dá)無(wú)明顯差異(P0.05)。干預(yù)后,BLys阻斷劑組和TLR-4阻斷劑組的TLR-4 m RNA、IL-6、IL-17、TNF-α、抗ds DNA抗體、C3、ESR和CRP較干預(yù)前明顯降低(P0.05),IL-2較干預(yù)前明顯增高(P0.05)。與野生對(duì)照組比,其余組別的TLR-4 m RNA、IL-6、IL-17、TNF-α、IL-2、C3、ESR和CRP表達(dá)干預(yù)前后均存在差異(P0.05)。與空白對(duì)照組比,BLys阻斷劑和TLR-4阻斷劑組HE和Masson染色均有明顯改善。結(jié)論BLys和TLR-4可能是參與SLE的發(fā)生發(fā)展,機(jī)理可能與調(diào)節(jié)免疫炎癥反應(yīng)有關(guān)。
[Abstract]:Objective to study the role and possible mechanism of Toll like receptor -4 Toll-like receptors-4 (TLR-4) and B lymphocyte stimulating factor B lymphocyte stimulator (BLys4) in systemic lupus erythematosus (SLE) transgenic mice, and to provide a new target for the treatment of SLE.Methods Thirty SPF grade EB virus membrane antigen BLLF1 transgenic female mice were randomly divided into control group (n = 10) and TLR-4 blocker group (n = 10).The wild-type mice of SPF grade were selected as wild control group. BLys antagonist group was treated with anti- monoclonal antibody 500mg / d, intraperitoneal injection of anti-human TLR-4 antibody 250mg / d, intraperitoneal injection of anti-human TLR-4 antibody 250mg / d, wild control group and blank control group.Group A received intraperitoneal injection of the same amount of normal saline.After 10 days of continuous feeding, the levels of TLR-4 m RNA were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in sterile caudal vein. The levels of IL-17, TNF- 偽 and IL-2 in tumor necrosis factor were detected by Elisa, and the titer of anti-DS DNA antibody was detected by immunoblot assay.Routine biochemical method was used to detect the levels of complement C3(complement 3, erythrocyte sedimentation rsr) and C-reactive protein C reaction protein (CRP) in the erythrocyte of mice. The kidneys of mice were stained with HE and Masson.Results there was no significant difference in BLys in peripheral blood mononuclear cells between wild control group and BLys blocker group, blank control group and TLR-4 blocker group. Compared with wild control group and BLys blocker group, the BLys of PBMC in blank control group and TLR-4 blocker group was significantly higher than that in control group and TLR-4 blocker group.It is suggested that EB virus membrane antigen BLLF1 transgenic mice can block the expression of PBMC BLys in SLE model.There was no significant difference in the expression of TLR-4 m RNA-IL-17TNF- 偽 and anti-DS DNA antibody C3TSR and CRP between the wild control group and the blank control group before and after intervention, but there was no significant difference in the expression of TLR-4 m RNA-6IL-17TNF- 偽 and anti-DS DNA antibody C3NSR and CRP between the blank control group and the TLR-4 blocker group before and after intervention.After intervention, the levels of TLR-4 m RNAs, IL-6 and IL-17 TNF- 偽, anti-DS DNA antibody C _ 3C _ 3N _ (2) and CRP in the TLR-4 antagonist group were significantly lower than those before the intervention, and the levels of P0.05 and IL-2 were significantly higher than those before the intervention.Compared with the wild control group, there were significant differences in the expression of TLR-4 m RNA-IL-6, IL-17, TNF- 偽, IL-2C3, ESR and CRP between the other groups before and after intervention (P 0.05).Compared with the blank control group, the HE and Masson staining of the two groups were significantly improved.Conclusion BLys and TLR-4 may be involved in the development of SLE, and the mechanism may be related to the regulation of immune inflammation.
【作者單位】： 山東中醫(yī)藥大學(xué)附屬醫(yī)院檢驗(yàn)科;
【分類號(hào)】：R-332;R593.241

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