中药抗病毒胶囊对RGH患者TLR9及对小鼠HSV-2感染TLR9、IFNα影响
摘要
一、目的
复发性生殖器疱疹(RGH)主要是由单纯疱疹病毒-2(HSV-2)感染生殖器部位皮肤粘膜所引起的炎症、水疱、溃疡性疾病,是最常见的性传播疾病(STD)之一。具有反复发作和缠绵难愈的特点。生殖器疱疹反复发作不仅给患者自己带来了沉重的心理负担和精神上的压力,而且影响家庭的稳定,从而导致患者生存质量低下,长期生活在性病的阴影之下。其长期的复发性和目前的不可治愈性,又加重了患者的经济负担。感染生殖器疱疹的孕妇会引起流产和新生儿死亡,并且生殖器疱疹反复发作的患者其宫颈癌、阴茎癌、前列腺癌和艾滋病的发生率明显上升。HSV感染增加了HIV感染的危险性,HSV-Ⅱ被视为HIV的辅助因子。因此HSV感染受到人们重视,Toll样受体(toll-like receptor,TLR)是机体通过感知微生物病原体并激活细胞直接产生免疫防御的天然免疫受体,是免疫细胞表面的模式识别受体(pattern recognition receptor,PRR),参与微生物病原体相关分子模式(pathogenassociated molecular patterns,PAMPs)的识别,从而诱导天然免疫应答。由于TLRs即能调节先天免疫,又能直接参与启动获得性免疫反应,因此TLRs对免疫系统功能有着非常重要的影响。TLR9主要表达于B细胞和浆细胞样前树突状细胞(plasmacytoidpredendritic cells,PDCs)内,可特异性地识别细菌和病毒DNA中丰富的未甲基化CpG基序(CpGDNA),通过MyD88依赖的信号传导途径激活NF-κB、AP1和IRF-7等转录因子和蛋白激酶,释放TNF-α、IL-6、IL-8等炎症介质和Ⅰ型干扰素(IFN-α/β),介导急性炎症反应,并发挥抗病毒作用。现有的证据表明,许多中药可通过多种途径或环节提高机体抗感染免疫力,由此不难推测,中药提高机体免疫系统对病原体的识别和杀伤能力,以及诱导、调节更有效的免疫防御反应,与TLR及其相关信号分子密切相关,二者之间存在着天然的联系。因此,根据中医理论,在宝贵的中医药资源中寻求高效价廉的抗病毒药物,具有重要的现实意义和社会意义。本文以TLR9作为检验指标来观察中药抗病毒胶囊制剂对复发性生殖器疱疹患者的影响,并观察中药抗病毒胶囊制剂对小鼠攻击HSV-2病毒后TLR-9及IFNα的作用,并初步探讨了其发病机理及中药抗病毒胶囊的作用机制,为生殖器疱疹的临床治疗和实验研究提供了一些新的思路和方法。
二、方法
1.临床研究选择合格的30例复发性生殖器患者作为受试对象,给予抗病毒胶囊观察患者治疗前与治疗后3个月TOLL样受体9的比较,同时对患者的平均复发频率(次/3个月)、皮损愈合时间与治疗前进行比较。
2.实验研究分为2部分,第一部分选用C57BL/6小鼠,以抗病毒2号胶囊进行预防试验,提前7天给与抗病毒2号胶囊,然后攻击病毒后,12小时和7天后各取小鼠的血和阴道组织进行TLR9和IFNα检测。第二部分选用C57BL/6小鼠,以抗病毒1号胶囊进行治疗实验,以HSV-2病毒攻击阴道后,给与抗病毒1号胶囊服用,在攻击后12小时和7天后各取小鼠的血和阴道组织进行TLR9和IFNα检测。
三、结果
1.临床试验显示:患者治疗后的复发频率较治疗前明显减少,皮损愈合时间明显缩短(与治疗前比较,P均＜0.05,有显著性差异),治疗6个月与治疗3个月比较,差异无统计学意义(P＞0.05)。
2.患者治疗前TLR9含量与正常人比有统计学意义,且治疗后TLR9含量与治疗前相比差异无显著性。
3.实验研究的预防试验显示,提前给予抗病毒2号胶囊喂食小鼠,攻击病毒后预防2组TLR9含量与阳性对照1组相比差异有统计学意义,与预防1组比较,差异有统计学意义,预防2组和阳性对照1组与正常组比较差异有统计学意义。
4.实验研究治疗试验显示:在淋巴细胞TLR9含量显示:治疗1组与阳性对照1组相比差异无统计学意义,治疗1组和治疗2组相比亦差异无统计学意义。阴道组织均数比较:治疗2组与正常组比较、阳性对照1组与阳性对照2组、治疗1组与阳性1组、阳性1组与正常对照差异有统计学意义;治疗1组与治疗2组间比较无统计学意义。
5.在两组试验研究IFNα检测显示:在预防试验中IFNα含量在四组间无统计学差异,但是从含量来讲,预防2组TLR9含量高于阳性对照1组基本,预防组和阳性对照组TLR9含量均高于正常组。在治疗试验中IFNα含量四组间有统计学差异,治疗1组与阳性对照1组之间差异有显著意义,治疗1组与治疗2组间比较差异无显著意义。阳性对照1组与正常对照组比较有统计学意义。
四、结论
1.以TLR9测定作为抗病毒胶囊的评价指标,观察到患者治疗前TLR9含量与正常人比有统计学意义,且治疗后TLR9含量与治疗前相比统计无显著差异。说明抗病毒胶囊可以维持TLR9含量,从天然免疫方面探讨抗病毒胶囊在免疫调节方面的作用机制;同时亦观察到中药抗病毒胶囊制剂患者经治疗后的复发频率较治疗前明显减少,皮损愈合时间明显缩短,表明中药抗病毒胶囊制剂在HSV-2侵袭人体后诱导天然免疫,服用中药后使TLR9表达维持高水平,从而启动后天免疫发挥抗病毒作用,有效地提高临床疗效,减少复发频率,缩短皮损愈合时间,减轻患者的痛苦。
2.实验研究显示:在动物被HSV-2病毒攻击后,TLR9介导了HSV天然免疫,预防试验显示,中药提前喂食小鼠,中药的小分子可能与TLR9的活性部分结合,促进了TLR9活化,在病毒攻击时启动天然免疫时,TLR9含量增加;治疗试验显示,在病毒攻击时启动了天然免疫,经过中药治疗基本维持天然免疫。同时,预防和治疗实验显示:在启动天然免疫的同时,其信号传导的终点没有显著增加IFNα的量,可能是启动的1型IFN中的βγ或其他的细胞因子。
Objective
The Recurrent Genital Herpes(RGH)is a kind of frequently Transmitted Sexual Disease(TSD)mainly caused by simplex herpes virus-2(HSV-2).RGH is recurrent and difficult to cure,therefore,brings about great pressure to the patients and their families.The patients will have low quality of life and suffer from financial difficulties caused by the persisting effect of sexual disease.Pregnant women infected with genital herpes would suffer from abortion and neonatal deaths.A patient frequently infected with genital herpes risks higher chance to have womb cancer,penile cancer,prostate cancer and AIDS.HSV infection increases the risk of HIV infection,in which HSV-Ⅱacts as Cofactor for HIV,thus catches more and more attention.Toll-like receptor(TLR),the pattern recognition receptor,which enables the body to recognize the Microbial pathogens and activates cells to produce immune cells and participate in the recognition of pathogen associated molecular patterns (PAMPs)which are at the surface of immune cells,thus induces natural immune response of the body.TLRs have an essential effect on the immune system because TLRs can regulate innate immune as well as involving directly in the launch of acquired immune response.TLR9,mainly contained in B-cell and plasmacytoidpredendritic cells(PDCs),can specifically identify the CpG motifs(CpGDNA)which is rich in the DNA of bacteria and viruses,therefore, activates NF-κB、AP1 and IRF-7 to release TNF-a,IL-6,IL-8 and other inflammatory mediatory mediators and typeⅠinterferon(IIFN-s/β)to mediate acute inflammatory response and play an antiviral effect,through MyD88-dependent signal transduction pathway activated by NF-kB,AP1 and IRF-7 and other transcription factors and protein Kinase.Available evidence shows that Traditional Chinese Medicine(TCM)can improve the Anti-infection of the immunity in a variety of ways._It is expected that TCM improves the immune system to identify and kill pathogens,and induce more effective regulation of the immune defense response,which is closely related to LR and associated with the signal molecules.Thus,searching for efficient but low cost of antiviral drugs from the precious Chinese medicine resources has realistic and social significance.
The purpose of this paper is to take TLR9 as a testing target to observe the function of the Chinese Anti-virus Medicine Capsules(CAMC)on the patients with recurrent genital herpes,and to observe the impact of the CAMC on TLR-9 and IFN-a in the cells of the mice infected by HSV-2 virus.
Preliminary Study on the pathogenesis of RGH and mechanism of anti-viral medicine capsules will offer a new method and way for the future clinical treatment and experimental research of RGH.
Method
1.Clinical Research:Select 30 RGH patients as test target,comparative, compare TLR9 between patients before treatment and three months after treatment,at the same time,compare the average frequency of relapse(times/3 month)、Lesions healing time between before treatment after treatment.
2.Experimental Study:Divided into two parts,the first part feed the C57BL /6 mouse with number 2 Anti-virus capsules 5 days ahead of schedule,after 12 hours and 7 days,respectively get the mouse,s blood and vaginal organizations to test TLR9 and IFNα.At the same time,do a biopsy of vaginal organizations.PartⅡfeed the C57BL/6 mouse number 1 Anti-virus capsules after attack vagina with HSV-2 virus.After 12 hours and 7 days,respectively get the mouse,s blood and vaginal organizations to test TLR9 and IFNα.At the same time,do a biopsy of vaginal organizations.
Results
1.The frequency of recurrence reduces significantly after treatment than before treatment.The time of Lesion healing was significantly shorter. (Compare with before treatment,P＜0.05,there was a significant difference).The difference was not significant between 6 month after treatment and 3 month after treatment.(P＞0.05)
2.TLR9 in patients before treatment were more Statistical significant than normal.There was not a significant difference for TLR9 levels in patients after treatment and before treatment.
3.Experimental studies of the prevention trial show that:feed mice with number 2 Anti-virus capsule in advance,after Virus attacking,there was no significant statistical difference that TLR9 levels in the prevention of group 2 and in Positive control groupl.There was also no significant statistical difference comparing with the prevention of group 1.But it was statistically significant difference to compare these 3 groups with the normal group.
4.Experimental studies of treatment trial show that:Levels of TLR9 in Lymphocyte show that:it was no statistically significant difference to compare the treatment Group 1 with the control group1.it was no statistically significant difference to campare the treatment group1 with the treatment group2.Compare with average lewes of vaginal tissue:it was statistically significant difference to campare the treatment group2 with the normal group;the positive group1 with the positive group 2;the treatment group 1 with the treatment group 2;the positive group 1 with the normal group.But it was no statistically significant difference to compare the treatment group 1 with the treatment group 2..
5.IFNαDetection in two groups experimental Study shows that:in the prevention trial the IFN-αlevel in four groups were no statistical difference. However,from the terms of content,the prevention of group 2 was higher than the positive control group1,the prevention group and the prevention group were higher than the normal group.In the treatment trial IFNαlevels in four groups have statistical difference,there was significant difference to compare treatment Group 1 with positive control group 1 and compare treatment Group 1 with the normal group,but there was no difference to compare the treatment group 1 with the treatment group 2.
Conclusion
1.take TLR9 testing as to be evaluation of anti-virus capsules,we can find that compare with TLR9 levels between patients before treatment and normal people was Statistical significant,and there was not a significant difference for TLR9 levels in patients after treatment and before treatment.That mean Anti-virus capsules could be maintained TLR9 level.We researched Anti-virus capsules in the role of immune regulation from the natural immune area.the frequency of recurrence reduce significantly after treatment than before treatment And the time of Lesion healing was significantly shorter,that means Anti-virus medicine capsules,could improve clinical efficacy,reduced relapse frequency,shortened healing time lesions,alleviated the suffering of patients.
2.Experimental studies show that:after the animals were attacked by HSV-2 virus,TLR9 caused the innate immune HSV.Prevention trial showed that:feed mice with Chinese herb in advance,the small molecule of Chinese medicine may be combination with some activities of TLR9.Treatment trial showed that:it switched on natural immune when the virus was attacking after the Chinese medicine treated,it basic maintain natural immune.Prevention and treatment trial showed that:when the natural immune was switched on,the level of IFNαthe end of its signal transduction don,raised,it was possible startedγof Type 1 of IFN or other Cytokines..
复发性生殖器疱疹(RGH)主要是由单纯疱疹病毒-2(HSV-2)感染生殖器部位皮肤粘膜所引起的炎症、水疱、溃疡性疾病,是最常见的性传播疾病(STD)之一。具有反复发作和缠绵难愈的特点。生殖器疱疹反复发作不仅给患者自己带来了沉重的心理负担和精神上的压力,而且影响家庭的稳定,从而导致患者生存质量低下,长期生活在性病的阴影之下。其长期的复发性和目前的不可治愈性,又加重了患者的经济负担。感染生殖器疱疹的孕妇会引起流产和新生儿死亡,并且生殖器疱疹反复发作的患者其宫颈癌、阴茎癌、前列腺癌和艾滋病的发生率明显上升。HSV感染增加了HIV感染的危险性,HSV-Ⅱ被视为HIV的辅助因子。因此HSV感染受到人们重视,Toll样受体(toll-like receptor,TLR)是机体通过感知微生物病原体并激活细胞直接产生免疫防御的天然免疫受体,是免疫细胞表面的模式识别受体(pattern recognition receptor,PRR),参与微生物病原体相关分子模式(pathogenassociated molecular patterns,PAMPs)的识别,从而诱导天然免疫应答。由于TLRs即能调节先天免疫,又能直接参与启动获得性免疫反应,因此TLRs对免疫系统功能有着非常重要的影响。TLR9主要表达于B细胞和浆细胞样前树突状细胞(plasmacytoidpredendritic cells,PDCs)内,可特异性地识别细菌和病毒DNA中丰富的未甲基化CpG基序(CpGDNA),通过MyD88依赖的信号传导途径激活NF-κB、AP1和IRF-7等转录因子和蛋白激酶,释放TNF-α、IL-6、IL-8等炎症介质和Ⅰ型干扰素(IFN-α/β),介导急性炎症反应,并发挥抗病毒作用。现有的证据表明,许多中药可通过多种途径或环节提高机体抗感染免疫力,由此不难推测,中药提高机体免疫系统对病原体的识别和杀伤能力,以及诱导、调节更有效的免疫防御反应,与TLR及其相关信号分子密切相关,二者之间存在着天然的联系。因此,根据中医理论,在宝贵的中医药资源中寻求高效价廉的抗病毒药物,具有重要的现实意义和社会意义。本文以TLR9作为检验指标来观察中药抗病毒胶囊制剂对复发性生殖器疱疹患者的影响,并观察中药抗病毒胶囊制剂对小鼠攻击HSV-2病毒后TLR-9及IFNα的作用,并初步探讨了其发病机理及中药抗病毒胶囊的作用机制,为生殖器疱疹的临床治疗和实验研究提供了一些新的思路和方法。
二、方法
1.临床研究选择合格的30例复发性生殖器患者作为受试对象,给予抗病毒胶囊观察患者治疗前与治疗后3个月TOLL样受体9的比较,同时对患者的平均复发频率(次/3个月)、皮损愈合时间与治疗前进行比较。
2.实验研究分为2部分,第一部分选用C57BL/6小鼠,以抗病毒2号胶囊进行预防试验,提前7天给与抗病毒2号胶囊,然后攻击病毒后,12小时和7天后各取小鼠的血和阴道组织进行TLR9和IFNα检测。第二部分选用C57BL/6小鼠,以抗病毒1号胶囊进行治疗实验,以HSV-2病毒攻击阴道后,给与抗病毒1号胶囊服用,在攻击后12小时和7天后各取小鼠的血和阴道组织进行TLR9和IFNα检测。
三、结果
1.临床试验显示:患者治疗后的复发频率较治疗前明显减少,皮损愈合时间明显缩短(与治疗前比较,P均＜0.05,有显著性差异),治疗6个月与治疗3个月比较,差异无统计学意义(P＞0.05)。
2.患者治疗前TLR9含量与正常人比有统计学意义,且治疗后TLR9含量与治疗前相比差异无显著性。
3.实验研究的预防试验显示,提前给予抗病毒2号胶囊喂食小鼠,攻击病毒后预防2组TLR9含量与阳性对照1组相比差异有统计学意义,与预防1组比较,差异有统计学意义,预防2组和阳性对照1组与正常组比较差异有统计学意义。
4.实验研究治疗试验显示:在淋巴细胞TLR9含量显示:治疗1组与阳性对照1组相比差异无统计学意义,治疗1组和治疗2组相比亦差异无统计学意义。阴道组织均数比较:治疗2组与正常组比较、阳性对照1组与阳性对照2组、治疗1组与阳性1组、阳性1组与正常对照差异有统计学意义;治疗1组与治疗2组间比较无统计学意义。
5.在两组试验研究IFNα检测显示:在预防试验中IFNα含量在四组间无统计学差异,但是从含量来讲,预防2组TLR9含量高于阳性对照1组基本,预防组和阳性对照组TLR9含量均高于正常组。在治疗试验中IFNα含量四组间有统计学差异,治疗1组与阳性对照1组之间差异有显著意义,治疗1组与治疗2组间比较差异无显著意义。阳性对照1组与正常对照组比较有统计学意义。
四、结论
1.以TLR9测定作为抗病毒胶囊的评价指标,观察到患者治疗前TLR9含量与正常人比有统计学意义,且治疗后TLR9含量与治疗前相比统计无显著差异。说明抗病毒胶囊可以维持TLR9含量,从天然免疫方面探讨抗病毒胶囊在免疫调节方面的作用机制;同时亦观察到中药抗病毒胶囊制剂患者经治疗后的复发频率较治疗前明显减少,皮损愈合时间明显缩短,表明中药抗病毒胶囊制剂在HSV-2侵袭人体后诱导天然免疫,服用中药后使TLR9表达维持高水平,从而启动后天免疫发挥抗病毒作用,有效地提高临床疗效,减少复发频率,缩短皮损愈合时间,减轻患者的痛苦。
2.实验研究显示:在动物被HSV-2病毒攻击后,TLR9介导了HSV天然免疫,预防试验显示,中药提前喂食小鼠,中药的小分子可能与TLR9的活性部分结合,促进了TLR9活化,在病毒攻击时启动天然免疫时,TLR9含量增加;治疗试验显示,在病毒攻击时启动了天然免疫,经过中药治疗基本维持天然免疫。同时,预防和治疗实验显示:在启动天然免疫的同时,其信号传导的终点没有显著增加IFNα的量,可能是启动的1型IFN中的βγ或其他的细胞因子。
Objective
The Recurrent Genital Herpes(RGH)is a kind of frequently Transmitted Sexual Disease(TSD)mainly caused by simplex herpes virus-2(HSV-2).RGH is recurrent and difficult to cure,therefore,brings about great pressure to the patients and their families.The patients will have low quality of life and suffer from financial difficulties caused by the persisting effect of sexual disease.Pregnant women infected with genital herpes would suffer from abortion and neonatal deaths.A patient frequently infected with genital herpes risks higher chance to have womb cancer,penile cancer,prostate cancer and AIDS.HSV infection increases the risk of HIV infection,in which HSV-Ⅱacts as Cofactor for HIV,thus catches more and more attention.Toll-like receptor(TLR),the pattern recognition receptor,which enables the body to recognize the Microbial pathogens and activates cells to produce immune cells and participate in the recognition of pathogen associated molecular patterns (PAMPs)which are at the surface of immune cells,thus induces natural immune response of the body.TLRs have an essential effect on the immune system because TLRs can regulate innate immune as well as involving directly in the launch of acquired immune response.TLR9,mainly contained in B-cell and plasmacytoidpredendritic cells(PDCs),can specifically identify the CpG motifs(CpGDNA)which is rich in the DNA of bacteria and viruses,therefore, activates NF-κB、AP1 and IRF-7 to release TNF-a,IL-6,IL-8 and other inflammatory mediatory mediators and typeⅠinterferon(IIFN-s/β)to mediate acute inflammatory response and play an antiviral effect,through MyD88-dependent signal transduction pathway activated by NF-kB,AP1 and IRF-7 and other transcription factors and protein Kinase.Available evidence shows that Traditional Chinese Medicine(TCM)can improve the Anti-infection of the immunity in a variety of ways._It is expected that TCM improves the immune system to identify and kill pathogens,and induce more effective regulation of the immune defense response,which is closely related to LR and associated with the signal molecules.Thus,searching for efficient but low cost of antiviral drugs from the precious Chinese medicine resources has realistic and social significance.
The purpose of this paper is to take TLR9 as a testing target to observe the function of the Chinese Anti-virus Medicine Capsules(CAMC)on the patients with recurrent genital herpes,and to observe the impact of the CAMC on TLR-9 and IFN-a in the cells of the mice infected by HSV-2 virus.
Preliminary Study on the pathogenesis of RGH and mechanism of anti-viral medicine capsules will offer a new method and way for the future clinical treatment and experimental research of RGH.
Method
1.Clinical Research:Select 30 RGH patients as test target,comparative, compare TLR9 between patients before treatment and three months after treatment,at the same time,compare the average frequency of relapse(times/3 month)、Lesions healing time between before treatment after treatment.
2.Experimental Study:Divided into two parts,the first part feed the C57BL /6 mouse with number 2 Anti-virus capsules 5 days ahead of schedule,after 12 hours and 7 days,respectively get the mouse,s blood and vaginal organizations to test TLR9 and IFNα.At the same time,do a biopsy of vaginal organizations.PartⅡfeed the C57BL/6 mouse number 1 Anti-virus capsules after attack vagina with HSV-2 virus.After 12 hours and 7 days,respectively get the mouse,s blood and vaginal organizations to test TLR9 and IFNα.At the same time,do a biopsy of vaginal organizations.
Results
1.The frequency of recurrence reduces significantly after treatment than before treatment.The time of Lesion healing was significantly shorter. (Compare with before treatment,P＜0.05,there was a significant difference).The difference was not significant between 6 month after treatment and 3 month after treatment.(P＞0.05)
2.TLR9 in patients before treatment were more Statistical significant than normal.There was not a significant difference for TLR9 levels in patients after treatment and before treatment.
3.Experimental studies of the prevention trial show that:feed mice with number 2 Anti-virus capsule in advance,after Virus attacking,there was no significant statistical difference that TLR9 levels in the prevention of group 2 and in Positive control groupl.There was also no significant statistical difference comparing with the prevention of group 1.But it was statistically significant difference to compare these 3 groups with the normal group.
4.Experimental studies of treatment trial show that:Levels of TLR9 in Lymphocyte show that:it was no statistically significant difference to compare the treatment Group 1 with the control group1.it was no statistically significant difference to campare the treatment group1 with the treatment group2.Compare with average lewes of vaginal tissue:it was statistically significant difference to campare the treatment group2 with the normal group;the positive group1 with the positive group 2;the treatment group 1 with the treatment group 2;the positive group 1 with the normal group.But it was no statistically significant difference to compare the treatment group 1 with the treatment group 2..
5.IFNαDetection in two groups experimental Study shows that:in the prevention trial the IFN-αlevel in four groups were no statistical difference. However,from the terms of content,the prevention of group 2 was higher than the positive control group1,the prevention group and the prevention group were higher than the normal group.In the treatment trial IFNαlevels in four groups have statistical difference,there was significant difference to compare treatment Group 1 with positive control group 1 and compare treatment Group 1 with the normal group,but there was no difference to compare the treatment group 1 with the treatment group 2.
Conclusion
1.take TLR9 testing as to be evaluation of anti-virus capsules,we can find that compare with TLR9 levels between patients before treatment and normal people was Statistical significant,and there was not a significant difference for TLR9 levels in patients after treatment and before treatment.That mean Anti-virus capsules could be maintained TLR9 level.We researched Anti-virus capsules in the role of immune regulation from the natural immune area.the frequency of recurrence reduce significantly after treatment than before treatment And the time of Lesion healing was significantly shorter,that means Anti-virus medicine capsules,could improve clinical efficacy,reduced relapse frequency,shortened healing time lesions,alleviated the suffering of patients.
2.Experimental studies show that:after the animals were attacked by HSV-2 virus,TLR9 caused the innate immune HSV.Prevention trial showed that:feed mice with Chinese herb in advance,the small molecule of Chinese medicine may be combination with some activities of TLR9.Treatment trial showed that:it switched on natural immune when the virus was attacking after the Chinese medicine treated,it basic maintain natural immune.Prevention and treatment trial showed that:when the natural immune was switched on,the level of IFNαthe end of its signal transduction don,raised,it was possible startedγof Type 1 of IFN or other Cytokines..
引文
[1]丁伟.生殖器疱疹的治疗现况[J].中国药师.2005,8(7):600-602.
[2]Ramjee G,Williams B,Gouws E,et al.The Impact of Incident and Prevalent Herpes Simplex Virus-2 Infection on the Incidence of HIV-1 Infection Among Commercial Sex Workers in South Africa[J].jAIDS Journal of Acquired Immune Deficiency Syndromes.2005,39(3):333-339.
[3]Celum C L.The interaction between herpes simplex virus and human immunodeficiency virus[J].Herpes.2004,11(Suppl 1):36-45.
[4]Sardana K,Sehgal V N.Genital ulcer disease and human immunodeficiency virus:a focus.[J].International Journal of Dermatology.2005,44(5):391-405.
[5]梁国均,邵长庚.全国性病流行现状和趋势分析[J].中国性病艾滋病防治.2001:3-5.
[6]禤国维,范瑞强.皮肤性病中医治疗全书[Z].广州:广东科技出版社,1996.
[7]谭新华,陆德铭.中医外科学[Z].北京:人民卫生出版社,1999.
[8]欧阳恒,杨志波.主编[Z].第1版.北京:人民军医出版社,2000277-278.
[9]Corey L.The current trend in genital herpes.Progress in prevention.[J].Sex Transm Dis.1994,21(2 Suppl):38-44.
[10]Mertz G J.Genital herpes simplex virus infections[J].The Medical clinics of North America Med Clin North Am.1990,74(6):1433-1454.
[11]Lavoie S R,Kaplowitz L G.Management of genital herpes infection.[J].Semin Dermatol.1994,13(4):248-255.
[12]Sasadeusz J J,Sacks S L.Herpes latency,meningitis,radiculomyelopathy and disseminated infection.[J].Genitourin Med.1994,70(6):369-377.
[13]Koutsky L A,Ashley R L,Holmes K K,et al.The frequency of unrecognized type 2 herpes simplex virus infection among women.Implications for the control of genital herpes.[J].Sex Transm Dis.1990,17(2):90-94.
[14]Lowhagen G B,Jansen E,Nordenfelt E,et al.Epidemiology of genital herpes infections in Sweden.[J].Acta Derm Venereol.1990,70(4):330-334.
[15]Ross J D,Smith I W,Elton R A.The epidemiology of herpes simplex types 1 and 2 infection of the genital tract in Edinburgh 1978-1991[J].Genitourinary medicine Genitourin Med.1993,69(5):381-383.
[16]Weiss H.Epidemiology of herpes simplex virus type 2 infection in the developing world[J].Herpes.2004,11 Suppl 1:24-35.
[17]Uuskula A,Nygard-kibur M,Cowan F M,et al.The burden of infection with herpes simplex virus type 1 and type 2:seroprevalence study in Estonia[J].Scandinavian journal of infectious diseases Scand J Infect Dis.2004,36(10):727-732.
[18]Kesson A M.Management of neonatal herpes simplex virus infection[J].Paediatric drugs Paediatr Drugs.2001,3(2):81-90.
[19]Ramjee G,Williams B,Gouws E,et al.The Impact of Incident and Prevalent Herpes Simplex Virus-2 Infection on the Incidence of HIV-1 Infection Among Commercial Sex Workers in South Africa.[J].JAIDS Journal of Acquired Immune Deficiency Syndromes.2005,39(3):333.
[20]Brown Z A,Wald A,Morrow R A,et al.Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant[J].Jama.2003,289(2):203-209.
[21]ACOG practice bulletin.Management of herpes in pregnancy.Number 8October 1999.Clinical management guidelines for obstetrician-gynecologists[J].International journal of gynaecology and obstetrics:the official organ of the International Federation of Gynaecology and Obstetrics Int J Gynaecol Obstet.2000,68(2):165-173.
[22]Landry M L,Mullangi P,Nee P,et al.Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes[J].The Journal of pediatrics J Pediatr.2005,146(6):836-838.
[23]钱起丰,郭红卫.复发性生殖器疱疹患者外周血CD3~+T细胞内细胞因子的检测[J].中华皮肤科杂志.2001,34(003):195-197.
[24]Mezentseva M V,Narovlyansky A N,Scherbenko V E,et al.Analysis of the interferon status and cytokine profile in patients with genital herpes.[J].Russ J Immunol.2002,7(2):167-174.
[25]Singh R,Kumar A,Creery W D,et al.Dysregulated expression of IFN-[gamma]and Ih-10 and impaired IFN-[gamma]-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.[J].Clinical & Experimental Immunolozy.2003,133(1):97.
[26]Shurshalina A V,Veryasov V N,Sukhikh G T.The ratio of cytokine levels in genital herpes during various phases of infection[J].Bulletin of experimental biology and medicine Bull Exp Biol Med.2001,132(1):660-662.
[27]Tanigawa M,Bigger J E,Kanter M Y,et al.Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye[J].Investigative ophthalmology & visual science Invest Ophthalmol Via Sci.2000,41(1):132-137.
[28]Eriksson K,Bellner L,Gorander S,et al.CD4(+)T-cell responses to herpes simplex virus type 2(HSV-2)glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals[J].The Journal of general virology J Gen Virol.2004,85(Pt 8):2139-2147.
[29]Thebeau L G,Morrison L A.Mechanism of reduced T-cell effector functions and class-switched antibody responses to herpes simplex virus type 2 inthe absence of B7 costimulation[J].J Virol.2003,77(4):2426-2435.
[30]Xu M,Lepisto A J,Hendricks R L.CD154 signaling regulates the Th1response to herpes simplex virus-1 and inflammation in infected corneas[J].J Immunol.2004,173(2):1232-1239.
[31]Yokota S,Yokosawa N,Okabayashi T,et al.Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway[J].Journal of virology J Virol.2004,78(12):6282-6286.
[32]Cao L,Martin A,Polakos N,et al.Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts[]].Journal of neuroimmunology J Neuroimmunol.2004,156(1-2):21-30.
[33]Swanson J M.Genital herpes and prevention of HIV infection:the report of a study in progress[J].J Assoc Nurses AIDS Care.1992,3(3):30-36.
[34]Keller M L,Jadack R A,Mims L F.Perceived stressors and coping responses in persons with recurrent genital herpes[J].Research in nursing & health Res Nuts Health.1991,14(6):421-430.
[35]苏铭,麦士兴,周琛.复发性生殖器疱疹患者心理健康状况的研究[J].河北医学.2004,10(008):702-703.
[36]Dibble S L,Swanson J M.Gender differences for the predictors of depression in young adults with genital herpes[J].Public health nursing (Boston,Mass Public Health Nurs.2000,17(3):187-194.
[37]胡晓燕,许敏,陈磊,等.复发性生殖器疱疹患者的心理健康状况及其影响因素[J].解放军护理杂志.2006,23(006):29-30.
[38]周淑华.女性生殖器单纯疱疹感染[J].国外医学:皮肤性病学分册.1998,24(001):34-37.
[39]许志学,许文庆.药物与心理治疗控制生殖器疱疹复发的探讨[J].广西医科大学学报.2002,19(004):536-537.
[40]Wald A,Zeh J,Selke S,et al.Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons[J].New England Journal of Medicine.2000,342(12):844.
[41]Boselli F,Chiossi G,Bortolamasi M,et al.Prevalence and determinants of genital shedding of herpes simplex virus among women attending Italian colposcopy clinics[J].European journal of obstetrics,gynecology,and reproductive biology Eur J Obstet Gynecol Reprod Biol.2005,118(1):86-90.
[42]Wald A,Zeh J,Barnum G,et al.Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir[J].Annals of internal medicine Ann Intern med.1996,124(1 Pt 1):8-15.
[43]Wald A,Zeh J,Selke S,et al.Virologic characteristics of subclinical and symptomatic genital herpes infections[J].The New England journal of medicine N Engl J med.1995,333(12):770-775.
[44]Armstrong G L,Schillinger J,Markowitz L,et al.Incidence of herpes simplex virus type 2 infection in the United States[J].American journal of epidemiology Am J Epidemiol.2001,153(9):912-920.
[45]Brown Z A,Selke S,Zeh J,et al.The Acquisition of Herpes Simplex Virus during Pregnancy[J].New England Journal of Medicine.1997,337(8):509.
[46]Brown Z A,Wald A,Morrow R A,et al.Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant[J].Jama.2003,289(2):203-209.
[47]Kimberlin D W.Neonatal herpes simplex infection[J].Clinical microbiology reviews Clin Microbiol Rev.2004,17(1):1-13.
[48]Sexually transmitted diseases treatment guidelines 2002.Centers for Disease Control and Prevention[]].MMWR Recomm Rep.2002,51(RR-6):1-78.
[49]张志礼.中医性病学[Z].江西:江西科学出版社,1991.
[50]徐宜厚.徐宜厚皮肤病临床经验辑要[Z].北京:中国医药科技出版社,1998.
[51]檀虎亮.辨证分期治疗原发性生殖器疱疹40例[J].山西中医.2003,19(002):22-23.
[52]刘若缨,杨玉峰,杨瑛,等.中药治疗复发性生殖器疱疹及其免疫调节作用的研究[J].中医药学刊.2004,22(009):1696-1697.
[53]冯桥.“知柏柴苓汤”治疗复发性生殖器疱疹41例[J].江苏中医药.2003.24(001):29-30.
[54]张剑,杨文信,叶田.养阴祛邪汤治疗复发性生殖器疱疹临床观察[J].中国皮肤性病学杂志.2004,18(009):565-565.
[55]杨玉峰,杜少辉.温胆汤加减治疗生殖器疱疹的临床研究[J].河北中医药学报.2000,15(003):10-11.
[56]杨嘉鑫.热疮饮治疗复发性生殖器疱疹121例[J].江苏中医.2000,21(6):33.
[57]晏勇,刘长山,陈希琳,等.花草清毒汤治疗生殖器疱疹60例[J].江西中医药.2007,38(5):45.
[58]杨志波,欧阳恒.黄白液治疗复发性生殖器疱疹的临床疗效观察[J].中国麻风皮肤病杂志.2002,18(001):60-60.
[59]周耀湘,彭建梅,李红,等.疱疹合剂1号治疗生殖器疱疹及对外周血T淋巴细胞亚群影响的临床研究[J].新中医.2006,38(003):36-37.
[60]马秀珍,步焕.玉屏风散加味治疗生殖器疱疹41例[J].医学动物防制.2005,21(5):330-331.
[61]林夏,林林.自拟龙虎疱疹汤治疗复发性生殖器疱疹23例疗效观察[J].皮肤病与性病.2000,22(002):51-52.
[62]曲卫毅,耿银,宋绍波,等1.综合治疗复发性生殖器疱疹31例[J].中医外治杂志.2005,14(006):33-33.
[63]易恒安,黄捷.苍耳子软膏治疗生殖器疱疹的临床观察[J].中国药房.2006,17(011):842-843.
[64]王更生,王桂元.儿茶外用治疗初发性生殖器疱疹39例[J].中医外治杂志.2001,10(006):42-43.
[65]肖美芳,黄捷.苍耳子油外用治疗生殖器疱疹临床观察[J].江西中医药.2004.35(004):40-40.
[66]杜维祥,贠清亮.祛毒洗液治疗生殖器疱疹的临床观察[J].山东中医杂志.2003,22(012):727-727.
[67]张宁.藤黄外用治疗生殖器疱疹患者的临床疗效和实验室研究[J].中华皮肤科杂志.2000(03).
[68]刘锦霞.外用中药加味珍珠散治疗生殖器疱疹50例临床观察[J].
[69]窦海忠,郭健,王冬梅,等.中西医结合治疗复发性生殖器疱疹的临床观察[J].现代中西医结合杂志.2007,16(012):1654-1654.
[70]萨那巴特尔董,白彦搭娜.中药内外合用治疗生殖器疱疹36例[J].中国民间疗法.2002,10(001):32-32.
[71]张丰川,李元文,周德瑛.中药疱疹净治疗复发性生殖器疱疹30例疗效观察[J].中国麻风皮肤病杂志.2003,19(002):155-156.
[72]孙维斌.中医药治疗生殖器疱疹30例[J].新中医.1999,31(010):47-47.
[73]卢俊明,沈一山.中西医结合治疗复发性生殖器疱疹58例[J].医药导报.2007:06.
[74]吴宏斌.中西医结合治疗生殖器疱疹60例分析[J].中国中西医结合皮肤性病学杂志.2006,5(003):163-164.
[75]杨永茂,沈敏娟,杨桂兰.中西医结合治疗复发性生殖器疱疹55例疗效观察[J].甘肃中医.2007,20(010):16-17.
[76]潘仕雄,包红波,江光明,等.抗毒合剂结合膦甲酸钠治疗复发性生殖器疱疹38例[J].陕西中医学院学报.2007:04.
[77]余良思.复发性生殖器疱疹综合治疗效果观察[J].浙江预防医学.2007,19(011):87-87.
[78]李谦,丁仁明.自拟扶正败毒汤预防复发性生殖器疱疹复发疗效观察[J].中医药临床杂志.2006,18(001):62-63.
[79]高贵云.中西药联合治疗生殖器疱疹66例临床观察[J].湖南中医学院学报.2002,22(001):62-62.
[80]李郑生,张燕燕.中西药抑制疗法治疗复发性生殖器疱疹[J].传染病信息.2003,16(001):40-40.
[81]李云涛,徐瑞丽,王欣.中西医结合治疗复发性生殖器疱疹35例[J].中国艾滋病性病.2004,10(003):222-222.
[82]罗建凯.中西医结合治疗复发性生殖器疱疹42例[J].实用中医药杂志.2003,19(010):533-533.
[83]贺伟,孙彩梅.中西医结合治疗生殖器疱疹24例[J].中国中西医结合杂志.2000.20(002):109-109.
[84]黄哲均,刘洁,崔英,等.中西医结合治疗生殖器疱疹96例临床体会[J].中华医药文萃.2004,1(1):38-38.
[85]庞建平.中西医结合治疗生殖器疱疹减少复发的临床观察[J].中国中医药信息杂志.2003,10(004):62-63.
[86]Miller R L,Tomai M A,Harrison C J,et al.Immunomodulation as a treatment strategy for genital herpes:review of the evidence[J].International immunopharmacology Int Immunopharmacol.2002,2(4):443-451.
[87]刘恩让,陈冰,谢倩,等1.盐酸万乃洛韦抑制疗法预防生殖器疱疹复发的观察[J].中国皮肤性病学杂志.2004,18(001):21-22.
[88]阮建波,邓敏芝,朱瑞清,等.三种方案治疗复发性生殖器疱疹疗效的比较[J].岭南皮肤性病科杂志.2006,13(004):296-297.
[89]Dejesus E,Wald A,Warren T,et al.Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects[J].The Journal of infectious diseases J Infect Dis.2003,188(7):1009-1016.
[90]Baker D A,Blythe J G,Miller J M.Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes[J].Obstetrics and gynecology Obstet Gynecol.1999,94(1):103-106.
[91]赵林栋.胸腺肽加阿昔洛韦治疗复发性生殖器疱疹临床观察[J].中国皮肤性病学杂志.2002,16(001):35-36.
[92]吴志华.皮肤性病学[M].广东科技出版社,1992.
[93]顾有守.外用免疫调节剂咪喹莫特在皮肤科的应用[J].临床皮肤科杂志.2003,32(001):54-56.
[94]Pearson G W,Langley R G.Topical imiquimod[J].The Journal of dermatological treatment J Dermatolog Treat.2001,12(i):37-40.
[95]Garnett G P,Dubin G,Slaoui M,et al.The potential epidemiological impact of a genital herpes vaccine for women[J].Sexually transmitted infections Sex Transm Infect.2004,80(1):24-29.
[96]林尽染,徐金华.单纯疱疹病毒疫苗研究进展[J].国际病毒学杂志.2007,14(005):136-139.
[97]赵辨.临床皮肤病学[M][Z].南京:江苏科学技术出版社,2001. 情[J].医药导报.2007,26(002):170-171.
[99]张燕,张国娣.盐酸伐昔洛韦抑制疗法预防生殖器疱疹复发的临床观察[J].中国麻风皮肤病杂志.2007:08.
[100]齐欣,吴桂香,杨晓琳,等.更昔洛韦治疗顽固复发性生殖器疱疹30例疗效观察[J].中国冶金工业医学杂志.2007,24(z1):106-107.
[101]刘恩让,张书岭,王福喜,等.两种伐昔洛韦抑制疗法方案预防生殖器疱疹复发作用比较[J].中国医院用药评价与分析.2007:04.
[102]陈平,李舰艇.3种抗病毒药物治疗复发性生殖器疱疹的疗效观察[J].医药导报.2007,26(012):1436-1437.
[103]赵丽燕.窄频紫外线光疗联合阿昔洛韦治疗生殖器疱疹的疗效分析[J].中国误诊学杂志.2008,8(1):18-19.
[104]杨林海.中西医结合治疗生殖器疱疹的临床分析[J].中国性科学.2006,15(004):30-31.
[105]周军.伐昔洛韦加斯奇康治疗复发性生殖器疱疹95例疗效观察[J].贵州医药.2007,31(009):782-782.
[106]陈天雷.泛昔洛韦联合转移因子,胸腺肽治疗复发性生殖器疱疹的临床观察[J].中国麻风皮肤病杂志.2007,23(004):279-279.
[107]张洪明,王峰,孙明忠,等.左旋咪唑联合阿昔洛韦治疗复发性生殖器疱疹的疗效观察[J].四川医学.2006,27(011):1138-1139.
[108]陈祖榕.局部注射治疗复发性生殖器疱疹疗效观察[J].现代医药卫生.2007(7):07.
[109]方彦.拉米夫定治疗复发性生殖器疱疹疗效观察[J].中国皮肤性病学杂志.2007,21(009):520-520.
[110]王玉,杜晓娟,曾铁云,等.咪喹莫特治疗复发性生殖器疱疹33例[J].医药导报.2007,26(012):1438-1438.
[111]靳隽.铜绿假单胞菌制剂联合泛昔洛韦治疗复发性生殖器疱疹疗效观察[J].中国现代药物应用.2007,1(4):19-20.
[112]Tyrinz S K,Baker D,Snowden W.Valacyclovir for herpes simplex virus infection:lonz-term safety and sustained efficacy after 20 years'experience with acyclovir[J].The Journal of infectious diseases J Infect Dis.2002,186 Suppl 1:40-46.
[113]Mertz G J,Loveless M O,Levin M J,et al.Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women.A multicenter,double-blind,placebo-controlled trial.Collaborative Famciclovir Genital Herpes Research Group[J].Archives of internal medicine Arch Intern Med.1997,157(3):343-349.
[114]Fonnest G,De F F,Weber T.Neonatal herpes in Denmark 1977-1991.[J].Acta Obstet Gynecol Scand.1997,76(4):355-358.
[115]Watts D H,Brown Z A,Money D,et al.A double-blind,randomized,placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery.[J].American Journal of Obstetrics & Gynecology.2003,188(3):836.
[116]Casper C,Wald A.Condom use and the prevention of genital herpes acquisition[J].Herpes.2002,9(1):10-14.
[117]Braig S,Chanzy B.Management of genital herpes during pregnancy:the French experience[J].Herpes.2004,11(2):45-47.
[118]倪安红,徐祖森.生殖器疱疹防治进展[J].国外医学:皮肤性病学分册.2005,31(003):145-147.
[119]赖伟红.生殖器疱疹临床研究的某些进展[J].国外医学:皮肤性病学分册.2000,26(003):162-166.
[120]唐晓青,李春阳.生殖器疱疹的流行病学及预防与控制[J].中国麻风皮肤病杂志.2002,18(003):266-268.
[121]蔡碧珊,孙希凤,郑道城,等.性病患者健康知识水平对安全套使用态度的影响[J].岭南皮肤性病科杂志.2004,11(001):60-62.
[122]Zwane I T,Mngadi P T,Nxumalo M P.Adolescents' views on decision-making regarding risky sexual behaviour[J].International nursing review Int Nurs Rev.2004,51(1):15-22.
[123]Anderson K V,Bokla L,Nusslein-volhard C.Establishment of dorsal-ventral polarity in the Drosophila embryo:the induction of polarity by the Toll gene,product.[J].Cell.1985,42(3):791-798.
[124]Medzhitov R.Toll-like receptors and innate immunity.[J].Nat Rev Immunol.2001,1(2):135-145.
[125]Akira S.Toll-like receptors and innate immunity.[J].Adv Immunol.2001,78:1-56.
[126]Hamilton J F,Morrison P F,Chen M Y,et al.Heparin coinfusion during convection-enhanced delivery(CED)increases the distribution of the glial-derived neurotrophic factor(GDNF)ligand family in rat striatum and enhances the pharmacological activity of neurturin.[J].Exp Neurol.2001,168(1):155-161.
[127]Takeda K,Kaisho T,Akira S.Toll-like receptors.[J].Annu Rev Immunol. 2003,21:335-376.
[128]Janeway C A.Approaching the asymptote? Evolution and revolution in immunology.[J].Cold Spring Harb Symp Quant Biol.1989,54 Pt 1:1-13.
[129]Ahmad-nejad P,Hacker H,Rutz M,et al.Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments.[J].Eur J Immunol.2002,32(7):1958-1968.
[130]O N L,Fitzgerald K A,Bowie A G.The Toll-IL-1 receptor adaptor family grows to five members.[J].Trends Immunol.2003,24(6):286-290.
[131]Medzhitov R.Toll-like receptors and innate immunity.[J].Nat Rev Immunol.2001,1(2):135-145.
[132]Wagner H.The immunobiology of the TLR9 subfamily.[J].Trends Immunol.2004,25(7):381-386.
[133]Abe T,Hemmi H,Miyamoto H,et al.Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus.[J].J Virol.2005,79(5):2847-2858.
[134]Akira S,Takeda K.Toll-like receptor signalling.[J].Nat Rev Immunol.2004,4(7):499-511.
[135]阳凯,王琛.宿主细胞应答病毒感染的细胞信号转导研究新进展[J].生物化学与生物物理进展.2006,33(12):1138-1145.
[136]Hemmi H,Takeuchi O,Kawai T,et al.A Toll-like receptor recognizes bacterial DNA.[J].Nature.2000,408(6813):740-745.
[137]Shimosato T,Kitazawa H,Katoh S,et al.Swine Toll-like receptor 9(1)recognizes CpG motifs of human cell stimulant.[J].Biochim Biophys Acta.2003,1627(1):56-61.
[138]Takeshita F,Gursel I,Ishii K J,et al.Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9.[J].Semin Immunol.2004,16(1):17-22.
[139]De G E,Srinivas S,Kilkenny C,et al.Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis.[J].Genes Dev.2001,15(18):2433-2444.
[140]Yeo S J,Yoon J G,Hong S C,et al.CpG DNA induces self and cross-hyporesponsiveness of RAW264.7 cells in response to CpG DNA and lipopolysaccharide:alterations in IL-1 receptor-associated kinase expression.[J].J Immunol.2003,170(2):1052-1061.
[141]Takeshita F,Leifer C A,Gursel I,et al.Cutting edge:Role of Toll-like receptor 9 in CpG DNA-induced activation of human cells.[J].J Immunol.2001,167(7):3555-3558.
[142]An H,Xu H,Yu Y,et al.Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB,ERK and p38 MAPK signal pathways.[J].Immunol Lett.2002,81(3):165-169.
[143]Bottcher T,Von M M,Ebert S,et al.Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections.[J].Neurosci Lett.2003,344(1):17-20.
[144]Liu L,Zhou X,Shi J,et al.Toll-like receptor-9 induced by physical trauma mediates release of cytokines following exposure to CpG motif in mouse skin.[J].Immunology.2003,110(3):341-347.
[145]Sato A,Iwasaki A.Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments.[J].Proc Natl Acad Sci U S A.2004,101(46):16274-16279.
[146]Ashkar A A,Yao X D,Gill N,et al.Toll-like receptor(TLR)-3,but not TLR4,agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA.[J].J Infect Dis.2004,190(10):1841-1849.
[147]Ashkar A A,Bauer S,Mitchell W J,et al.Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication,but not entry,of herpes simplex virus type 2.[J].J Virol.2003,77(16):8948-8956.
[148]Harandi A Z,Eriksson K,Holmgren J.A protective role of locally administered immunostimulatory CpG oligodeoxynucleotide in a mouse model of genital herpes infection.[J].J Virol.2003,77(2):953-962.
[149]Pyles R B,Higgins D,Chalk C,et al.Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection.[J].J Virol.2002,76(22):11387-11396.
[150]Martin-orozco E,Kobayashi H,Van U J,et al.Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences.[J].Int Immunol.1999,11(7):1111-1118.
[151]Chuang T H,Lee J,Kline L,et al.Toll-like receptor 9 mediates CpG-DNA signaling.[J].J Leukoc Biol.2002,71(3):538-544.
[152]Takeshita F,Leifer C A,Gursel I,et al.Cutting edge:Role of Toll-like receptor 9 in CpG DNA-induced activation of human cells.[J].J Immunol.2001,167(7):3555-3558.
[153]Krieg A M,Yi A K,Schorr J,et al.The role of CpG dinucleotides in DNA vaccines.[J].Trends Microbiol.1998,6(1):23-27.
[154]Krieg A M.The role of CpG motifs in innate immunity.[J].Curr Opin Immunot.2000,12(1):35-43.
[155]Hong Z,Jiang Z,Liangxi W,et al.Chloroquine protects mice from challenge with CpG ODN and LPS by decreasing proinflammatory cytokine release.[J].Int Immunopharmacol.2004,4(2):223-234.
[156]Ahmad-nejad P,Hacker H,Rutz M,et al.Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments.[J].Eur J Immunol.2002,32(7):1958-1968.
[157]Wagner H.The immunobiology of the TLR9 subfamily.[J].Trends Immunol.2004,25(7):381-386.
[158]Hoshino K,Kaisho T,lwabe T,st al.Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation.[J].Int Immunol.2002,14(10):1225-1231.
[159]Hoebe K,Janssen E M,Kim S O,et al.Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways.[J].Nat Immunol.2003,4(12):1223-1229.
[160]Guiducci C,Ott G,Chan J H,et al.Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9activation.[J].J Exp Med.2006,203(8):1999-2008.
[161]Kerkmann M,Costa L T,Richter C,et al.Spontaneous formation of nucleic acid-based nanoparticles is responsible for high interferon-alpha induction by CpG-A in plasmacytoid dendritic cells.[J].J Biol Chem.2005,280(9):8086-8093.
[162]Krieg A M.CpG motifs in bacterial DNA and their immune effects.[J].Annu Rev Immunol.2002,20:709-760.
[163]Duramad O,Fearon K L,Chan J H,et al.IL-IO regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences.[J].Blood.2003,102(].3):4487-4492.
[164]Marshall J D,Fearon K,Abbate C,et al.Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions.[J].J Leukoc Biol.2003,73(6):781-792.
[165]Hartmann G,Battiany J,Poeck H,et al.Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. [J]. Eur J Immunol. 2003, 33(6): 1633-1641.
[166] Honda K, Yanai H, Negishi H, et al. IRF-7 is the master regulator of type-1 interferon-dependent immune responses. [J]. Nature. 2005, 434(7034): 772-777.
[167] Dalod M, Salazar-mather T P, Malmgaard L, et al. Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. [J]. J Exp Med. 2002, 195(4): 517-528.
[168] Stunz L L, Lenert P, Peckham D, et al. Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. [J]. Eur J Immunol. 2002, 32(5): 1212-1222.
[169] Yamamoto M, Yamazaki S, Uematsu S, et al. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. [J]. Nature. 2004, 430(6996): 218-222.
[170] Latz E, Schoenemeyer A, Visintin A, et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. [J]. Nat Immunol. 2004, 5(2): 190-198.
[171] Wu C C, Lee J, Raz E, et al. Necessity of oligonucleotide aggregation for toll-like receptor 9 activation. [J]. J Biol Chem. 2004, 279(32): 33071-33078.
[172] Takeshita F, Gursel I, Ishii K J, et al. Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9. [J]. Semin Immunol. 2004, 16(1): 17-22.
[173] Ashkar A A, Bauer S, Mitchell W J, et al. Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2. [J]. J Virol. 2003, 77(16): 8948-8956.
[174] Sajic D, Patrick A J, Rosenthal K L. Mucosal delivery of CpG oligodeoxynucleotides expands functional dendritic cells and macrophages in the vagina. [J]. Immunology. 2005, 114(2): 213-224.
[175] Marshall J D, Higgins D, Abbate C, et al. Polymyxin B enhances ISS-mediated immune responses across multiple species. [J]. Cell Immunol. 2004, 229(2): 93-105.
[176]Gill N,Rosenthal K L,Ashkar A A.NK and NKT cell-independent contribution of interleukin-15 to innate protection against mucosal viral infection.[J].J Virol.2005,79(7):4470-4478.
[177]Lund J,Sato A,Akira S,et al.Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells.[J].J Exp Med.2003,198(3):513-520.
[178]Asselin-paturel C,Boonstra A,Dalod M,et al.Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.[J].Nat Immunol.2001,2(12):1144-1150.
[179]Nakano H,Yanasita M,Gunn M D.CD11c(+)B220(+)Gr-1(+)cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells.[J].J Exp Med.2001,194(8):1171-1178.
[180]O K M,Hochrein H,Vremec D,et al.Mouse plasmacytoid cells:long-lived cells,heterogeneous in surface phenotype and function,that differentiate into CD8(+)dendritic cells only after microbial stimulus.[J].J Exp Med.2002,196(10):1307-1319.
[181]Leadbetter E A,Rifkin I R,Hohlbaum A M,et al.Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors.[J].Nature.2002,416(6881):603-607.
[182]Zhao X,Deak E,Soderberg K,et al.Vaginal submucosal dendritic cells,but not Langerhans cells,induce protective Th1 responses to herpes simplex virus-2.[J].J Exp Med.2003,197(2):153-162.
[183]Shen H,Iwasaki A.A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN-based vaginal microbicide.[J].J Clin Invest.2006,116(8):2237-2243.
[184]Duerst R J,Morrison L A.Innate Immunity to Herpes Simplex Virus Type 2[J].Viral Immunology.2003,16(4):475-490.
[185]伍晓春,陆豫.虎杖的药理作用及临床应用研究进展[J].中医药信息.2005,22(2):22.
[186]Medzhitov R,Preston-hurlburt P,Janeway J C.A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.[J].Nature.1997,388(6640):394-397.
[187]Takeda K,Akira S.Toll-like receptors in innate immunity[J].International Immunology.2005,17(1):1-14.
[188]Akira S,Uematsu S,Takeuchi O.Pathogen Recognition and Innate Immunity[J].Cell.2006,124(4):783-801.
[189]徐佩红,袁定芬,薛峰,等.生殖器疱疹患者外周血单个核细胞TLR9的表达及血清IL-12,IFN-γ水平的研究[J].诊断学理论与实践.2007:04.
[190]Cates J W.Estimates of the incidence and prevalence of sexually transmitted diseases in the United States.American Social Health Association Panel.[J].Sex Transm Dis.1999,26(4 Suppl):2-7.
[191]张锡宝,韩尔阳.广州市性病监测10年流行动态分析[J].中国皮肤性病学杂志.2002,16(001):17-20.
[192]O N L,Fitzgerald K A,Bowie A G.The Toll-IL-1 receptor adaptor family grows to five members[J].Trends in Immunology.2003,24(6):286-289.
[193]Akira S.Mammalian Toll-like receptors[J].Current Opinion in Immunology.2003,15(1):5-11.
[194]Partida-s S,Randall T D,Lund F E.Innate immunity is regulated by CD38,an ecto-enzyme with ADP-ribosyl cyclase activity[J].Microbes and Infection.2003,5(1):49-58.
[195]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].Proceedings of the National Academy of Sciences.2004,101(5):1315.
[196]Krug A,huker G D,Barchet W,et al.Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9.[J].Blood.2004,103(4):1433-1437.
[197]Hochrein H,Schlatter B,O K M,et al.Herpes simplex virus type-1 induces IFN-{alpba} production via Toll-like receptor 9-dependent and-independent pathways[J].Proceedings of the National Academy of Sciences.2004,101(31):11416.
[198]闻玉梅.天然免疫与中西医结合[J].中西医结合学报.2004,2(001):1-2.
[199]范瑞强,陈永锋.中药抗病毒胶囊治疗复发性生殖器疱疹139例临床观察[J].中医杂志.2002,43(009):670-680.
[200]王忠,王阶.后基因组时代中医证候组学研究的思考[J].中国中西医结合杂志.2001,21(008):621-623.
[2]Ramjee G,Williams B,Gouws E,et al.The Impact of Incident and Prevalent Herpes Simplex Virus-2 Infection on the Incidence of HIV-1 Infection Among Commercial Sex Workers in South Africa[J].jAIDS Journal of Acquired Immune Deficiency Syndromes.2005,39(3):333-339.
[3]Celum C L.The interaction between herpes simplex virus and human immunodeficiency virus[J].Herpes.2004,11(Suppl 1):36-45.
[4]Sardana K,Sehgal V N.Genital ulcer disease and human immunodeficiency virus:a focus.[J].International Journal of Dermatology.2005,44(5):391-405.
[5]梁国均,邵长庚.全国性病流行现状和趋势分析[J].中国性病艾滋病防治.2001:3-5.
[6]禤国维,范瑞强.皮肤性病中医治疗全书[Z].广州:广东科技出版社,1996.
[7]谭新华,陆德铭.中医外科学[Z].北京:人民卫生出版社,1999.
[8]欧阳恒,杨志波.主编[Z].第1版.北京:人民军医出版社,2000277-278.
[9]Corey L.The current trend in genital herpes.Progress in prevention.[J].Sex Transm Dis.1994,21(2 Suppl):38-44.
[10]Mertz G J.Genital herpes simplex virus infections[J].The Medical clinics of North America Med Clin North Am.1990,74(6):1433-1454.
[11]Lavoie S R,Kaplowitz L G.Management of genital herpes infection.[J].Semin Dermatol.1994,13(4):248-255.
[12]Sasadeusz J J,Sacks S L.Herpes latency,meningitis,radiculomyelopathy and disseminated infection.[J].Genitourin Med.1994,70(6):369-377.
[13]Koutsky L A,Ashley R L,Holmes K K,et al.The frequency of unrecognized type 2 herpes simplex virus infection among women.Implications for the control of genital herpes.[J].Sex Transm Dis.1990,17(2):90-94.
[14]Lowhagen G B,Jansen E,Nordenfelt E,et al.Epidemiology of genital herpes infections in Sweden.[J].Acta Derm Venereol.1990,70(4):330-334.
[15]Ross J D,Smith I W,Elton R A.The epidemiology of herpes simplex types 1 and 2 infection of the genital tract in Edinburgh 1978-1991[J].Genitourinary medicine Genitourin Med.1993,69(5):381-383.
[16]Weiss H.Epidemiology of herpes simplex virus type 2 infection in the developing world[J].Herpes.2004,11 Suppl 1:24-35.
[17]Uuskula A,Nygard-kibur M,Cowan F M,et al.The burden of infection with herpes simplex virus type 1 and type 2:seroprevalence study in Estonia[J].Scandinavian journal of infectious diseases Scand J Infect Dis.2004,36(10):727-732.
[18]Kesson A M.Management of neonatal herpes simplex virus infection[J].Paediatric drugs Paediatr Drugs.2001,3(2):81-90.
[19]Ramjee G,Williams B,Gouws E,et al.The Impact of Incident and Prevalent Herpes Simplex Virus-2 Infection on the Incidence of HIV-1 Infection Among Commercial Sex Workers in South Africa.[J].JAIDS Journal of Acquired Immune Deficiency Syndromes.2005,39(3):333.
[20]Brown Z A,Wald A,Morrow R A,et al.Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant[J].Jama.2003,289(2):203-209.
[21]ACOG practice bulletin.Management of herpes in pregnancy.Number 8October 1999.Clinical management guidelines for obstetrician-gynecologists[J].International journal of gynaecology and obstetrics:the official organ of the International Federation of Gynaecology and Obstetrics Int J Gynaecol Obstet.2000,68(2):165-173.
[22]Landry M L,Mullangi P,Nee P,et al.Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes[J].The Journal of pediatrics J Pediatr.2005,146(6):836-838.
[23]钱起丰,郭红卫.复发性生殖器疱疹患者外周血CD3~+T细胞内细胞因子的检测[J].中华皮肤科杂志.2001,34(003):195-197.
[24]Mezentseva M V,Narovlyansky A N,Scherbenko V E,et al.Analysis of the interferon status and cytokine profile in patients with genital herpes.[J].Russ J Immunol.2002,7(2):167-174.
[25]Singh R,Kumar A,Creery W D,et al.Dysregulated expression of IFN-[gamma]and Ih-10 and impaired IFN-[gamma]-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.[J].Clinical & Experimental Immunolozy.2003,133(1):97.
[26]Shurshalina A V,Veryasov V N,Sukhikh G T.The ratio of cytokine levels in genital herpes during various phases of infection[J].Bulletin of experimental biology and medicine Bull Exp Biol Med.2001,132(1):660-662.
[27]Tanigawa M,Bigger J E,Kanter M Y,et al.Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye[J].Investigative ophthalmology & visual science Invest Ophthalmol Via Sci.2000,41(1):132-137.
[28]Eriksson K,Bellner L,Gorander S,et al.CD4(+)T-cell responses to herpes simplex virus type 2(HSV-2)glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals[J].The Journal of general virology J Gen Virol.2004,85(Pt 8):2139-2147.
[29]Thebeau L G,Morrison L A.Mechanism of reduced T-cell effector functions and class-switched antibody responses to herpes simplex virus type 2 inthe absence of B7 costimulation[J].J Virol.2003,77(4):2426-2435.
[30]Xu M,Lepisto A J,Hendricks R L.CD154 signaling regulates the Th1response to herpes simplex virus-1 and inflammation in infected corneas[J].J Immunol.2004,173(2):1232-1239.
[31]Yokota S,Yokosawa N,Okabayashi T,et al.Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway[J].Journal of virology J Virol.2004,78(12):6282-6286.
[32]Cao L,Martin A,Polakos N,et al.Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts[]].Journal of neuroimmunology J Neuroimmunol.2004,156(1-2):21-30.
[33]Swanson J M.Genital herpes and prevention of HIV infection:the report of a study in progress[J].J Assoc Nurses AIDS Care.1992,3(3):30-36.
[34]Keller M L,Jadack R A,Mims L F.Perceived stressors and coping responses in persons with recurrent genital herpes[J].Research in nursing & health Res Nuts Health.1991,14(6):421-430.
[35]苏铭,麦士兴,周琛.复发性生殖器疱疹患者心理健康状况的研究[J].河北医学.2004,10(008):702-703.
[36]Dibble S L,Swanson J M.Gender differences for the predictors of depression in young adults with genital herpes[J].Public health nursing (Boston,Mass Public Health Nurs.2000,17(3):187-194.
[37]胡晓燕,许敏,陈磊,等.复发性生殖器疱疹患者的心理健康状况及其影响因素[J].解放军护理杂志.2006,23(006):29-30.
[38]周淑华.女性生殖器单纯疱疹感染[J].国外医学:皮肤性病学分册.1998,24(001):34-37.
[39]许志学,许文庆.药物与心理治疗控制生殖器疱疹复发的探讨[J].广西医科大学学报.2002,19(004):536-537.
[40]Wald A,Zeh J,Selke S,et al.Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons[J].New England Journal of Medicine.2000,342(12):844.
[41]Boselli F,Chiossi G,Bortolamasi M,et al.Prevalence and determinants of genital shedding of herpes simplex virus among women attending Italian colposcopy clinics[J].European journal of obstetrics,gynecology,and reproductive biology Eur J Obstet Gynecol Reprod Biol.2005,118(1):86-90.
[42]Wald A,Zeh J,Barnum G,et al.Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir[J].Annals of internal medicine Ann Intern med.1996,124(1 Pt 1):8-15.
[43]Wald A,Zeh J,Selke S,et al.Virologic characteristics of subclinical and symptomatic genital herpes infections[J].The New England journal of medicine N Engl J med.1995,333(12):770-775.
[44]Armstrong G L,Schillinger J,Markowitz L,et al.Incidence of herpes simplex virus type 2 infection in the United States[J].American journal of epidemiology Am J Epidemiol.2001,153(9):912-920.
[45]Brown Z A,Selke S,Zeh J,et al.The Acquisition of Herpes Simplex Virus during Pregnancy[J].New England Journal of Medicine.1997,337(8):509.
[46]Brown Z A,Wald A,Morrow R A,et al.Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant[J].Jama.2003,289(2):203-209.
[47]Kimberlin D W.Neonatal herpes simplex infection[J].Clinical microbiology reviews Clin Microbiol Rev.2004,17(1):1-13.
[48]Sexually transmitted diseases treatment guidelines 2002.Centers for Disease Control and Prevention[]].MMWR Recomm Rep.2002,51(RR-6):1-78.
[49]张志礼.中医性病学[Z].江西:江西科学出版社,1991.
[50]徐宜厚.徐宜厚皮肤病临床经验辑要[Z].北京:中国医药科技出版社,1998.
[51]檀虎亮.辨证分期治疗原发性生殖器疱疹40例[J].山西中医.2003,19(002):22-23.
[52]刘若缨,杨玉峰,杨瑛,等.中药治疗复发性生殖器疱疹及其免疫调节作用的研究[J].中医药学刊.2004,22(009):1696-1697.
[53]冯桥.“知柏柴苓汤”治疗复发性生殖器疱疹41例[J].江苏中医药.2003.24(001):29-30.
[54]张剑,杨文信,叶田.养阴祛邪汤治疗复发性生殖器疱疹临床观察[J].中国皮肤性病学杂志.2004,18(009):565-565.
[55]杨玉峰,杜少辉.温胆汤加减治疗生殖器疱疹的临床研究[J].河北中医药学报.2000,15(003):10-11.
[56]杨嘉鑫.热疮饮治疗复发性生殖器疱疹121例[J].江苏中医.2000,21(6):33.
[57]晏勇,刘长山,陈希琳,等.花草清毒汤治疗生殖器疱疹60例[J].江西中医药.2007,38(5):45.
[58]杨志波,欧阳恒.黄白液治疗复发性生殖器疱疹的临床疗效观察[J].中国麻风皮肤病杂志.2002,18(001):60-60.
[59]周耀湘,彭建梅,李红,等.疱疹合剂1号治疗生殖器疱疹及对外周血T淋巴细胞亚群影响的临床研究[J].新中医.2006,38(003):36-37.
[60]马秀珍,步焕.玉屏风散加味治疗生殖器疱疹41例[J].医学动物防制.2005,21(5):330-331.
[61]林夏,林林.自拟龙虎疱疹汤治疗复发性生殖器疱疹23例疗效观察[J].皮肤病与性病.2000,22(002):51-52.
[62]曲卫毅,耿银,宋绍波,等1.综合治疗复发性生殖器疱疹31例[J].中医外治杂志.2005,14(006):33-33.
[63]易恒安,黄捷.苍耳子软膏治疗生殖器疱疹的临床观察[J].中国药房.2006,17(011):842-843.
[64]王更生,王桂元.儿茶外用治疗初发性生殖器疱疹39例[J].中医外治杂志.2001,10(006):42-43.
[65]肖美芳,黄捷.苍耳子油外用治疗生殖器疱疹临床观察[J].江西中医药.2004.35(004):40-40.
[66]杜维祥,贠清亮.祛毒洗液治疗生殖器疱疹的临床观察[J].山东中医杂志.2003,22(012):727-727.
[67]张宁.藤黄外用治疗生殖器疱疹患者的临床疗效和实验室研究[J].中华皮肤科杂志.2000(03).
[68]刘锦霞.外用中药加味珍珠散治疗生殖器疱疹50例临床观察[J].
[69]窦海忠,郭健,王冬梅,等.中西医结合治疗复发性生殖器疱疹的临床观察[J].现代中西医结合杂志.2007,16(012):1654-1654.
[70]萨那巴特尔董,白彦搭娜.中药内外合用治疗生殖器疱疹36例[J].中国民间疗法.2002,10(001):32-32.
[71]张丰川,李元文,周德瑛.中药疱疹净治疗复发性生殖器疱疹30例疗效观察[J].中国麻风皮肤病杂志.2003,19(002):155-156.
[72]孙维斌.中医药治疗生殖器疱疹30例[J].新中医.1999,31(010):47-47.
[73]卢俊明,沈一山.中西医结合治疗复发性生殖器疱疹58例[J].医药导报.2007:06.
[74]吴宏斌.中西医结合治疗生殖器疱疹60例分析[J].中国中西医结合皮肤性病学杂志.2006,5(003):163-164.
[75]杨永茂,沈敏娟,杨桂兰.中西医结合治疗复发性生殖器疱疹55例疗效观察[J].甘肃中医.2007,20(010):16-17.
[76]潘仕雄,包红波,江光明,等.抗毒合剂结合膦甲酸钠治疗复发性生殖器疱疹38例[J].陕西中医学院学报.2007:04.
[77]余良思.复发性生殖器疱疹综合治疗效果观察[J].浙江预防医学.2007,19(011):87-87.
[78]李谦,丁仁明.自拟扶正败毒汤预防复发性生殖器疱疹复发疗效观察[J].中医药临床杂志.2006,18(001):62-63.
[79]高贵云.中西药联合治疗生殖器疱疹66例临床观察[J].湖南中医学院学报.2002,22(001):62-62.
[80]李郑生,张燕燕.中西药抑制疗法治疗复发性生殖器疱疹[J].传染病信息.2003,16(001):40-40.
[81]李云涛,徐瑞丽,王欣.中西医结合治疗复发性生殖器疱疹35例[J].中国艾滋病性病.2004,10(003):222-222.
[82]罗建凯.中西医结合治疗复发性生殖器疱疹42例[J].实用中医药杂志.2003,19(010):533-533.
[83]贺伟,孙彩梅.中西医结合治疗生殖器疱疹24例[J].中国中西医结合杂志.2000.20(002):109-109.
[84]黄哲均,刘洁,崔英,等.中西医结合治疗生殖器疱疹96例临床体会[J].中华医药文萃.2004,1(1):38-38.
[85]庞建平.中西医结合治疗生殖器疱疹减少复发的临床观察[J].中国中医药信息杂志.2003,10(004):62-63.
[86]Miller R L,Tomai M A,Harrison C J,et al.Immunomodulation as a treatment strategy for genital herpes:review of the evidence[J].International immunopharmacology Int Immunopharmacol.2002,2(4):443-451.
[87]刘恩让,陈冰,谢倩,等1.盐酸万乃洛韦抑制疗法预防生殖器疱疹复发的观察[J].中国皮肤性病学杂志.2004,18(001):21-22.
[88]阮建波,邓敏芝,朱瑞清,等.三种方案治疗复发性生殖器疱疹疗效的比较[J].岭南皮肤性病科杂志.2006,13(004):296-297.
[89]Dejesus E,Wald A,Warren T,et al.Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects[J].The Journal of infectious diseases J Infect Dis.2003,188(7):1009-1016.
[90]Baker D A,Blythe J G,Miller J M.Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes[J].Obstetrics and gynecology Obstet Gynecol.1999,94(1):103-106.
[91]赵林栋.胸腺肽加阿昔洛韦治疗复发性生殖器疱疹临床观察[J].中国皮肤性病学杂志.2002,16(001):35-36.
[92]吴志华.皮肤性病学[M].广东科技出版社,1992.
[93]顾有守.外用免疫调节剂咪喹莫特在皮肤科的应用[J].临床皮肤科杂志.2003,32(001):54-56.
[94]Pearson G W,Langley R G.Topical imiquimod[J].The Journal of dermatological treatment J Dermatolog Treat.2001,12(i):37-40.
[95]Garnett G P,Dubin G,Slaoui M,et al.The potential epidemiological impact of a genital herpes vaccine for women[J].Sexually transmitted infections Sex Transm Infect.2004,80(1):24-29.
[96]林尽染,徐金华.单纯疱疹病毒疫苗研究进展[J].国际病毒学杂志.2007,14(005):136-139.
[97]赵辨.临床皮肤病学[M][Z].南京:江苏科学技术出版社,2001. 情[J].医药导报.2007,26(002):170-171.
[99]张燕,张国娣.盐酸伐昔洛韦抑制疗法预防生殖器疱疹复发的临床观察[J].中国麻风皮肤病杂志.2007:08.
[100]齐欣,吴桂香,杨晓琳,等.更昔洛韦治疗顽固复发性生殖器疱疹30例疗效观察[J].中国冶金工业医学杂志.2007,24(z1):106-107.
[101]刘恩让,张书岭,王福喜,等.两种伐昔洛韦抑制疗法方案预防生殖器疱疹复发作用比较[J].中国医院用药评价与分析.2007:04.
[102]陈平,李舰艇.3种抗病毒药物治疗复发性生殖器疱疹的疗效观察[J].医药导报.2007,26(012):1436-1437.
[103]赵丽燕.窄频紫外线光疗联合阿昔洛韦治疗生殖器疱疹的疗效分析[J].中国误诊学杂志.2008,8(1):18-19.
[104]杨林海.中西医结合治疗生殖器疱疹的临床分析[J].中国性科学.2006,15(004):30-31.
[105]周军.伐昔洛韦加斯奇康治疗复发性生殖器疱疹95例疗效观察[J].贵州医药.2007,31(009):782-782.
[106]陈天雷.泛昔洛韦联合转移因子,胸腺肽治疗复发性生殖器疱疹的临床观察[J].中国麻风皮肤病杂志.2007,23(004):279-279.
[107]张洪明,王峰,孙明忠,等.左旋咪唑联合阿昔洛韦治疗复发性生殖器疱疹的疗效观察[J].四川医学.2006,27(011):1138-1139.
[108]陈祖榕.局部注射治疗复发性生殖器疱疹疗效观察[J].现代医药卫生.2007(7):07.
[109]方彦.拉米夫定治疗复发性生殖器疱疹疗效观察[J].中国皮肤性病学杂志.2007,21(009):520-520.
[110]王玉,杜晓娟,曾铁云,等.咪喹莫特治疗复发性生殖器疱疹33例[J].医药导报.2007,26(012):1438-1438.
[111]靳隽.铜绿假单胞菌制剂联合泛昔洛韦治疗复发性生殖器疱疹疗效观察[J].中国现代药物应用.2007,1(4):19-20.
[112]Tyrinz S K,Baker D,Snowden W.Valacyclovir for herpes simplex virus infection:lonz-term safety and sustained efficacy after 20 years'experience with acyclovir[J].The Journal of infectious diseases J Infect Dis.2002,186 Suppl 1:40-46.
[113]Mertz G J,Loveless M O,Levin M J,et al.Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women.A multicenter,double-blind,placebo-controlled trial.Collaborative Famciclovir Genital Herpes Research Group[J].Archives of internal medicine Arch Intern Med.1997,157(3):343-349.
[114]Fonnest G,De F F,Weber T.Neonatal herpes in Denmark 1977-1991.[J].Acta Obstet Gynecol Scand.1997,76(4):355-358.
[115]Watts D H,Brown Z A,Money D,et al.A double-blind,randomized,placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery.[J].American Journal of Obstetrics & Gynecology.2003,188(3):836.
[116]Casper C,Wald A.Condom use and the prevention of genital herpes acquisition[J].Herpes.2002,9(1):10-14.
[117]Braig S,Chanzy B.Management of genital herpes during pregnancy:the French experience[J].Herpes.2004,11(2):45-47.
[118]倪安红,徐祖森.生殖器疱疹防治进展[J].国外医学:皮肤性病学分册.2005,31(003):145-147.
[119]赖伟红.生殖器疱疹临床研究的某些进展[J].国外医学:皮肤性病学分册.2000,26(003):162-166.
[120]唐晓青,李春阳.生殖器疱疹的流行病学及预防与控制[J].中国麻风皮肤病杂志.2002,18(003):266-268.
[121]蔡碧珊,孙希凤,郑道城,等.性病患者健康知识水平对安全套使用态度的影响[J].岭南皮肤性病科杂志.2004,11(001):60-62.
[122]Zwane I T,Mngadi P T,Nxumalo M P.Adolescents' views on decision-making regarding risky sexual behaviour[J].International nursing review Int Nurs Rev.2004,51(1):15-22.
[123]Anderson K V,Bokla L,Nusslein-volhard C.Establishment of dorsal-ventral polarity in the Drosophila embryo:the induction of polarity by the Toll gene,product.[J].Cell.1985,42(3):791-798.
[124]Medzhitov R.Toll-like receptors and innate immunity.[J].Nat Rev Immunol.2001,1(2):135-145.
[125]Akira S.Toll-like receptors and innate immunity.[J].Adv Immunol.2001,78:1-56.
[126]Hamilton J F,Morrison P F,Chen M Y,et al.Heparin coinfusion during convection-enhanced delivery(CED)increases the distribution of the glial-derived neurotrophic factor(GDNF)ligand family in rat striatum and enhances the pharmacological activity of neurturin.[J].Exp Neurol.2001,168(1):155-161.
[127]Takeda K,Kaisho T,Akira S.Toll-like receptors.[J].Annu Rev Immunol. 2003,21:335-376.
[128]Janeway C A.Approaching the asymptote? Evolution and revolution in immunology.[J].Cold Spring Harb Symp Quant Biol.1989,54 Pt 1:1-13.
[129]Ahmad-nejad P,Hacker H,Rutz M,et al.Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments.[J].Eur J Immunol.2002,32(7):1958-1968.
[130]O N L,Fitzgerald K A,Bowie A G.The Toll-IL-1 receptor adaptor family grows to five members.[J].Trends Immunol.2003,24(6):286-290.
[131]Medzhitov R.Toll-like receptors and innate immunity.[J].Nat Rev Immunol.2001,1(2):135-145.
[132]Wagner H.The immunobiology of the TLR9 subfamily.[J].Trends Immunol.2004,25(7):381-386.
[133]Abe T,Hemmi H,Miyamoto H,et al.Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus.[J].J Virol.2005,79(5):2847-2858.
[134]Akira S,Takeda K.Toll-like receptor signalling.[J].Nat Rev Immunol.2004,4(7):499-511.
[135]阳凯,王琛.宿主细胞应答病毒感染的细胞信号转导研究新进展[J].生物化学与生物物理进展.2006,33(12):1138-1145.
[136]Hemmi H,Takeuchi O,Kawai T,et al.A Toll-like receptor recognizes bacterial DNA.[J].Nature.2000,408(6813):740-745.
[137]Shimosato T,Kitazawa H,Katoh S,et al.Swine Toll-like receptor 9(1)recognizes CpG motifs of human cell stimulant.[J].Biochim Biophys Acta.2003,1627(1):56-61.
[138]Takeshita F,Gursel I,Ishii K J,et al.Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9.[J].Semin Immunol.2004,16(1):17-22.
[139]De G E,Srinivas S,Kilkenny C,et al.Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis.[J].Genes Dev.2001,15(18):2433-2444.
[140]Yeo S J,Yoon J G,Hong S C,et al.CpG DNA induces self and cross-hyporesponsiveness of RAW264.7 cells in response to CpG DNA and lipopolysaccharide:alterations in IL-1 receptor-associated kinase expression.[J].J Immunol.2003,170(2):1052-1061.
[141]Takeshita F,Leifer C A,Gursel I,et al.Cutting edge:Role of Toll-like receptor 9 in CpG DNA-induced activation of human cells.[J].J Immunol.2001,167(7):3555-3558.
[142]An H,Xu H,Yu Y,et al.Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB,ERK and p38 MAPK signal pathways.[J].Immunol Lett.2002,81(3):165-169.
[143]Bottcher T,Von M M,Ebert S,et al.Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections.[J].Neurosci Lett.2003,344(1):17-20.
[144]Liu L,Zhou X,Shi J,et al.Toll-like receptor-9 induced by physical trauma mediates release of cytokines following exposure to CpG motif in mouse skin.[J].Immunology.2003,110(3):341-347.
[145]Sato A,Iwasaki A.Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments.[J].Proc Natl Acad Sci U S A.2004,101(46):16274-16279.
[146]Ashkar A A,Yao X D,Gill N,et al.Toll-like receptor(TLR)-3,but not TLR4,agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA.[J].J Infect Dis.2004,190(10):1841-1849.
[147]Ashkar A A,Bauer S,Mitchell W J,et al.Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication,but not entry,of herpes simplex virus type 2.[J].J Virol.2003,77(16):8948-8956.
[148]Harandi A Z,Eriksson K,Holmgren J.A protective role of locally administered immunostimulatory CpG oligodeoxynucleotide in a mouse model of genital herpes infection.[J].J Virol.2003,77(2):953-962.
[149]Pyles R B,Higgins D,Chalk C,et al.Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection.[J].J Virol.2002,76(22):11387-11396.
[150]Martin-orozco E,Kobayashi H,Van U J,et al.Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences.[J].Int Immunol.1999,11(7):1111-1118.
[151]Chuang T H,Lee J,Kline L,et al.Toll-like receptor 9 mediates CpG-DNA signaling.[J].J Leukoc Biol.2002,71(3):538-544.
[152]Takeshita F,Leifer C A,Gursel I,et al.Cutting edge:Role of Toll-like receptor 9 in CpG DNA-induced activation of human cells.[J].J Immunol.2001,167(7):3555-3558.
[153]Krieg A M,Yi A K,Schorr J,et al.The role of CpG dinucleotides in DNA vaccines.[J].Trends Microbiol.1998,6(1):23-27.
[154]Krieg A M.The role of CpG motifs in innate immunity.[J].Curr Opin Immunot.2000,12(1):35-43.
[155]Hong Z,Jiang Z,Liangxi W,et al.Chloroquine protects mice from challenge with CpG ODN and LPS by decreasing proinflammatory cytokine release.[J].Int Immunopharmacol.2004,4(2):223-234.
[156]Ahmad-nejad P,Hacker H,Rutz M,et al.Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments.[J].Eur J Immunol.2002,32(7):1958-1968.
[157]Wagner H.The immunobiology of the TLR9 subfamily.[J].Trends Immunol.2004,25(7):381-386.
[158]Hoshino K,Kaisho T,lwabe T,st al.Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation.[J].Int Immunol.2002,14(10):1225-1231.
[159]Hoebe K,Janssen E M,Kim S O,et al.Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways.[J].Nat Immunol.2003,4(12):1223-1229.
[160]Guiducci C,Ott G,Chan J H,et al.Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9activation.[J].J Exp Med.2006,203(8):1999-2008.
[161]Kerkmann M,Costa L T,Richter C,et al.Spontaneous formation of nucleic acid-based nanoparticles is responsible for high interferon-alpha induction by CpG-A in plasmacytoid dendritic cells.[J].J Biol Chem.2005,280(9):8086-8093.
[162]Krieg A M.CpG motifs in bacterial DNA and their immune effects.[J].Annu Rev Immunol.2002,20:709-760.
[163]Duramad O,Fearon K L,Chan J H,et al.IL-IO regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences.[J].Blood.2003,102(].3):4487-4492.
[164]Marshall J D,Fearon K,Abbate C,et al.Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions.[J].J Leukoc Biol.2003,73(6):781-792.
[165]Hartmann G,Battiany J,Poeck H,et al.Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. [J]. Eur J Immunol. 2003, 33(6): 1633-1641.
[166] Honda K, Yanai H, Negishi H, et al. IRF-7 is the master regulator of type-1 interferon-dependent immune responses. [J]. Nature. 2005, 434(7034): 772-777.
[167] Dalod M, Salazar-mather T P, Malmgaard L, et al. Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. [J]. J Exp Med. 2002, 195(4): 517-528.
[168] Stunz L L, Lenert P, Peckham D, et al. Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. [J]. Eur J Immunol. 2002, 32(5): 1212-1222.
[169] Yamamoto M, Yamazaki S, Uematsu S, et al. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. [J]. Nature. 2004, 430(6996): 218-222.
[170] Latz E, Schoenemeyer A, Visintin A, et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. [J]. Nat Immunol. 2004, 5(2): 190-198.
[171] Wu C C, Lee J, Raz E, et al. Necessity of oligonucleotide aggregation for toll-like receptor 9 activation. [J]. J Biol Chem. 2004, 279(32): 33071-33078.
[172] Takeshita F, Gursel I, Ishii K J, et al. Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9. [J]. Semin Immunol. 2004, 16(1): 17-22.
[173] Ashkar A A, Bauer S, Mitchell W J, et al. Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2. [J]. J Virol. 2003, 77(16): 8948-8956.
[174] Sajic D, Patrick A J, Rosenthal K L. Mucosal delivery of CpG oligodeoxynucleotides expands functional dendritic cells and macrophages in the vagina. [J]. Immunology. 2005, 114(2): 213-224.
[175] Marshall J D, Higgins D, Abbate C, et al. Polymyxin B enhances ISS-mediated immune responses across multiple species. [J]. Cell Immunol. 2004, 229(2): 93-105.
[176]Gill N,Rosenthal K L,Ashkar A A.NK and NKT cell-independent contribution of interleukin-15 to innate protection against mucosal viral infection.[J].J Virol.2005,79(7):4470-4478.
[177]Lund J,Sato A,Akira S,et al.Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells.[J].J Exp Med.2003,198(3):513-520.
[178]Asselin-paturel C,Boonstra A,Dalod M,et al.Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.[J].Nat Immunol.2001,2(12):1144-1150.
[179]Nakano H,Yanasita M,Gunn M D.CD11c(+)B220(+)Gr-1(+)cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells.[J].J Exp Med.2001,194(8):1171-1178.
[180]O K M,Hochrein H,Vremec D,et al.Mouse plasmacytoid cells:long-lived cells,heterogeneous in surface phenotype and function,that differentiate into CD8(+)dendritic cells only after microbial stimulus.[J].J Exp Med.2002,196(10):1307-1319.
[181]Leadbetter E A,Rifkin I R,Hohlbaum A M,et al.Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors.[J].Nature.2002,416(6881):603-607.
[182]Zhao X,Deak E,Soderberg K,et al.Vaginal submucosal dendritic cells,but not Langerhans cells,induce protective Th1 responses to herpes simplex virus-2.[J].J Exp Med.2003,197(2):153-162.
[183]Shen H,Iwasaki A.A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN-based vaginal microbicide.[J].J Clin Invest.2006,116(8):2237-2243.
[184]Duerst R J,Morrison L A.Innate Immunity to Herpes Simplex Virus Type 2[J].Viral Immunology.2003,16(4):475-490.
[185]伍晓春,陆豫.虎杖的药理作用及临床应用研究进展[J].中医药信息.2005,22(2):22.
[186]Medzhitov R,Preston-hurlburt P,Janeway J C.A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.[J].Nature.1997,388(6640):394-397.
[187]Takeda K,Akira S.Toll-like receptors in innate immunity[J].International Immunology.2005,17(1):1-14.
[188]Akira S,Uematsu S,Takeuchi O.Pathogen Recognition and Innate Immunity[J].Cell.2006,124(4):783-801.
[189]徐佩红,袁定芬,薛峰,等.生殖器疱疹患者外周血单个核细胞TLR9的表达及血清IL-12,IFN-γ水平的研究[J].诊断学理论与实践.2007:04.
[190]Cates J W.Estimates of the incidence and prevalence of sexually transmitted diseases in the United States.American Social Health Association Panel.[J].Sex Transm Dis.1999,26(4 Suppl):2-7.
[191]张锡宝,韩尔阳.广州市性病监测10年流行动态分析[J].中国皮肤性病学杂志.2002,16(001):17-20.
[192]O N L,Fitzgerald K A,Bowie A G.The Toll-IL-1 receptor adaptor family grows to five members[J].Trends in Immunology.2003,24(6):286-289.
[193]Akira S.Mammalian Toll-like receptors[J].Current Opinion in Immunology.2003,15(1):5-11.
[194]Partida-s S,Randall T D,Lund F E.Innate immunity is regulated by CD38,an ecto-enzyme with ADP-ribosyl cyclase activity[J].Microbes and Infection.2003,5(1):49-58.
[195]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].Proceedings of the National Academy of Sciences.2004,101(5):1315.
[196]Krug A,huker G D,Barchet W,et al.Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9.[J].Blood.2004,103(4):1433-1437.
[197]Hochrein H,Schlatter B,O K M,et al.Herpes simplex virus type-1 induces IFN-{alpba} production via Toll-like receptor 9-dependent and-independent pathways[J].Proceedings of the National Academy of Sciences.2004,101(31):11416.
[198]闻玉梅.天然免疫与中西医结合[J].中西医结合学报.2004,2(001):1-2.
[199]范瑞强,陈永锋.中药抗病毒胶囊治疗复发性生殖器疱疹139例临床观察[J].中医杂志.2002,43(009):670-680.
[200]王忠,王阶.后基因组时代中医证候组学研究的思考[J].中国中西医结合杂志.2001,21(008):621-623.