目的 探討小鼠感染肺炎衣原體后肺組織TOLL 樣受體( TLR) 2 的基因表達(dá)變化及其信號(hào)傳導(dǎo)機(jī)制。方法 TLR4 基因缺失小鼠( C3H/HeJ) 96 只, 隨機(jī)分為對(duì)照組、模型組、SB203580 組和PDTC 組, 每組24 只。每組分別按1、4、7、14 d 各分4 個(gè)小組, 每小組6 只。對(duì)照組鼻內(nèi)接種二磷酸蔗糖( 2sp) 緩沖液, 模型組和干預(yù)組均給予約4. 0 ×106 IFU/mL( 0. 04 mL) 的肺炎衣原體鼻內(nèi)接種,SB203580 組和PDTC 組在接種完肺炎衣原體后分別立即腹腔注射相應(yīng)的p38 蛋白激酶( p38MAPK)抑制劑SB203580 ( 100 mg/ kg ) 或核因子κB ( NF-κB) 抑制劑吡咯烷二硫氨基甲酸( PDTC)( 50 mg/kg) 。分別于接種后第1、4、7 及14 d 處死小鼠, RT-PCR 法檢測(cè)肺組織TLR2 mRNA 的表達(dá),ELISA 法測(cè)定肺組織勻漿腫瘤壞死因子α( TNF-α) 的含量, 同時(shí)觀察肺組織病理變化。結(jié)果 小鼠感染肺炎衣原體后肺組織TLR2 mRNA 表達(dá)迅速升高, 以第4 d 和第7 d 明顯, 14 d 以后開始下降。PDTC 早期干預(yù)可在一定程度上抑制肺臟組織TLR2 mRNA 表達(dá), 并在感染高峰期抑制明顯。SB203580 對(duì)小鼠肺組織TLR2 mRNA 表達(dá)也有明顯抑制。感染肺炎衣原體后, 肺組織TNF-α表達(dá)水平顯著高于正常組, SB203580 和PDTC 對(duì)小鼠肺組織TNF-α表達(dá)均有抑制作用, SB203580 對(duì)TNF-α的抑制作用強(qiáng)于PDTC。結(jié)果 小鼠感染肺炎衣原體后, 可引起TLR2 表達(dá)的增加。對(duì)p38MAPK 和 NF-κB 的干預(yù)均影響TLR2 的表達(dá)以及炎癥介質(zhì)的釋放, 提示肺炎衣原體可能是通過TLR2 /MAPK 和TLR2 /NF-κB 通路導(dǎo)致肺部炎癥反應(yīng)。
引用本文： 董靜,施毅,宋勇,宋應(yīng)健. 小鼠肺炎衣原體肺炎TLR2基因表達(dá)及信號(hào)傳導(dǎo)機(jī)制的實(shí)驗(yàn)研究. 中國呼吸與危重監(jiān)護(hù)雜志, 2009, 09(3): 267-270. doi: 復(fù)制
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- 1. Armant MA, Fenton MJ. Toll-like receptors: a family of patternrecognition receptors in mammals. Genome Biol, 2002, 3: 3011-3016.
- 2. Perera PY, Mayadas TN, Takeuchi O, et al. CD11b /CD18 acts in concert with CD14 and Toll-like receptor ( TLR ) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J Immunol,2001, 166: 574-581.
- 3. Costa CP, Kirschning CJ, Busch D, et al. Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae. Eur J Immunol, 2002, 32: 2460-2470.
- 4. Prebeck S, Kirschning C, Dürr S, et al. Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumonoae-induced activation of dendritic cells. J Immunol, 2001, 167: 3316-3323.
- 5. Sasu S, LaVerda D, Qureshi N, et al. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44 /p42 mitogen-activated protein kinase activation. Circ Res, 2001, 89: 244-250.
- 6. Netea MG, Kullberg BJ, Galama JM, et al. Non-LPS components of Chlamydia pneumonoae stimulate cytokinr production through Tolllike receptor 2-dependent pathways. Eur J Immunol, 2002, 32: 1188-1195.
- 7. Bulut Y, Faure E, Thomas L, et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. Immunol,2002, 168: 1435-1440.
- 8. 董靜, 施毅, 宋勇, 等. 小鼠感染肺炎衣原體后肺組織TLR2、TLR4 基因表達(dá)變化及意義. 中國抗感染化療雜志, 2006, 6: 92-96.
- 9. Cuzzocrea S, Chatterjee PK, Mazzon E, et al. Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation. Br J Pharmacol, 2002, 135: 496-510.
- 10. Wissel H, Schulz C, Koehne P, et al. Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-αand MIP-2 via an NF-κB pathway in rat type II pneumocytes. Respir Res, 2005, 6: 51-56.