目的：研究咖啡鞣酸（chlorogenic acid，CGA）在单纯疱疹病毒-1（herpes simplex virus-1，HSV-1）感染的BV2小胶质细胞中的抗炎作用。方法：用HSV-1刺激的BV2小胶质细胞建立单纯疱疹病毒性脑炎（herpes simplex virus encephalitis，HSE）的细胞模型，然后用不同浓度梯度的CGA进行处理。通过MTT法测定细胞存活率。分别通过real-time PCR（RT-PCR）和Western blotting测定Toll样受体TLR2、TLR9 mRNA和蛋白质的表达。结果：HSV-1感染的BV2小胶质细胞经CGA处理后细胞存活率显著升高（P<0.05）。与正常组相比，HSV-1组TLR2、TLR9的mRNA和蛋白的水平显著升高（P<0.05），而CGA作用后显著降低HSV-1诱导的TLR2、TLR9表达（P<0.05）。结论：CGA通过降低TLR2、TLR9的表达抑制HSE中的炎症反应，可为HSE的抗炎治疗提供新的治疗策略。

[1] SAWLESHWARKAR S,DWYER D E.Antivirals for herpes simplex viruses[J].BMJ,2015,351:h3350.
[2] DERESIEWICZ R L,THALER S J,HSU L,et al.Clinical and neuroradiographic manifestations of eastern equine encephalitis[J].NEJM,1997,336(26):1867-1874.
[3] PARISI S G,BASSO M,DEL V C,et al.Viral infections of the central nervous system in elderly patients:a retrospective study[J].IJD,2016,44:8-10.
[4] BEIG F K,MALIK A,RIZVI M,et al.Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh,India[J].IJID,2010,14(2):e141-146.
[5] RECHENCHOSKI D Z,FACCIN-GALHARDI L C,LINHARES R E,et al.Herpesvirus:an underestimated virus[J].Folia Microbiol (Praha),2017,62(2):151-156.
[6] CURTIS A M,BELLET M M,SASSONE-CORSI P,et al.Circadian clock proteins and immunity[J].Immunity,2014,40(2):178-186.
[7] HANAMSAGAR R,HANKE M L,KIELIAN T.Toll-like receptor (TLR) and inflammasome actions in the central nervous system[J].Trends Immunol,2012,33(7):333-342.
[8] YAN Y,LIU N,HOU N,et al.Chlorogenic acid inhibits hepatocellular carcinoma in vitro and in vivo[J].JNB,2017,46:68-73.
[9] ABRANKO L,CLIFFORD M N.An unambiguous nomenclature for the acyl-quinic acids commonly known as chlorogenic acids[J].JAFC,2017,65(18):3602-3608.
[10] SAWLANI V.Diffusion-weighted imaging and apparent diffusion coefficient evaluation of herpes simplex encephalitis and Japanese encephalitis[J].JNS,2009,287(1-2):221-226.
[11] MARANDU T F,ODURO J D,BORKNER L,et al.Immune protection against virus challenge in aging mice is not affected by latent herpesviral infections[J].JV,2015,89(22):11715-11717.
[12] CHOI B K,KIM Y H,CHOI J H,et al.Unified immune modulation by 4-1BB triggering leads to diverse effects on disease progression in vivo[J].Cytokine,2011,55(3):420-428.
[13] HOSSAIN M J,TANASESCU R,GRAN B.TLR2:an innate immune checkpoint in multiple sclerosis[J].Oncotarget,2015,6(34):35131-35132.
[14] LIU Y,YIN H,ZHAO M,et al.TLR2 and TLR4 in autoimmune diseases:a comprehensive review[J].Clin Rev Allergy Immunol,2014,47(2):136-147.
[15] RANSOHOFF R M,BROWN M A.Innate immunity in the central nervous system[J].JCI,2012,122(4):1164-1171.
[16] HANAGATA N.CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers,infectious diseases,and allergies[J].IJN,2017,12:515-531.
[17] DOWNES C E,CRACK P J.Neural injury following stroke:are Toll-like receptors the link between the immune system and the CNS[J].BJP,2010,160(8):1872-1888.
[18] DORING C,REGEN T,GERTIG U,et al.A presumed antagonistic LPS identifies distinct functional organization of TLR4 in mouse microglia[J].Glia,2017,65(7):1176-1185.
[19] KUO A H,SCHEEREN F A.Cell-intrinsic TLR2/MyD88 pathway in breast and colon cancer[J].Cell Cycle,2014,13(24):3785-3786.
[20] LI J,FABER M,DIETZSCHOLD B,et al.The role of toll-like receptors in the induction of immune responses during rabies virus infection[J].AVR,2011,79:115-126.
[21] RODRIGUES F L,FAIS R S,TOSTES R C,et al.There is a link between erectile dysfunction and heart failure:it could be inflammation[J].Curr Drug Targets,2015,16(5):442-450.
[22] BAGHERJ V,ASKARI A,ARABABADI M K,et al.Can Toll-Like Receptor (TLR) 2 be considered as a new target for immunotherapy against hepatitis B infection[J].Hum Immunol,2014,75(6):549-554.
[23] RAJASAGI N K,ROUSE B T.IL-2 complex treatment amplifies CD8(+) T cell mediated immunity following herpes simplex virus-1 infection[J].Microbes Infect,2016,18(12):735-746.
[24] KURT-JONES E A,CHAN M,ZHOU S,et al.Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis[J].PNAS U S A,2004,101(5):1315-1320.