中药参芪合剂辅助治疗隐球菌性脑膜炎临床研究
摘要
目的中药参芪合剂辅助治疗隐球菌性脑膜炎临床治疗效果。方法收集2015年10至2017年6月入住我院神经内科的成人(>16岁)非艾滋病隐球菌性脑膜炎患者共61例,随机分成病例组30例(中药辅助治疗组)及对照组31例(单纯抗真菌治疗组)。所有患者均按2010年美国IDSA隐球菌病诊治指南,予两性霉素B+氟康唑诱导治疗,病例组加用中药辅助治疗,中药参芪合剂药方为金银花20g、黄芩15g、黄芪30g、苦参15g、蛇床子30g,每日1次。所有患者均于治疗前及治疗后7d、14d、28d、60d留取脑脊液,比较2组患者脑脊液隐球菌计数、IFN-γ和TNF-α浓度的差异,分析中药参芪合剂辅助治疗隐球菌性脑膜炎的治疗效果并研究可能的作用机制。结果病例组隐球菌计数(个/u L)于治疗14d(10.26±2.25 vs 12.35±2.86,P<0.01)、28d(5.65±1.37 vs 8.62±2.28,P<0.01)、60d(3.56±1.65 vs 5.68±1.76,P<0.01)明显低于对照组;随治疗干预,病例组脑脊液IFN-γ浓度(pg/ml)逐渐上升,并且在治疗14d(25.32±4.38 vs 20.12±2.65,P<0.01)、28d(28.84±3.16 vs 20.56±2.76,P<0.01)、60d(30.65±2.26 vs 20.74±2.64,P<0.01)明显高于对照组,TNF-α浓度(pg/ml)在治疗28d(30.26±5.12 vs 23.61±3.86,P<0.01)、60d(30.65±2.26 vs 23.96±4.12,P<0.01)明显高于对照组;病例组外周血CD4+和CD8+淋巴细胞计数(个/μl)在治疗28d(412.96±40.82 vs 380.69±43.28,P<0.01和613.46±60.83 vs 575.54±61.75,P=0.02)、60d(424.68±45.23 vs 382.24±44.67,P<0.01和625.86±41.33 vs 570.87±62.54,P<0.01)明显高于对照组。结论中药参芪合剂可用于辅助治疗隐球菌性脑膜炎,有利于隐球菌的快速清除,改善临床症状,其可能的作用机制为通过免疫调节机体产生IFN-γ和TNF-α等细胞因子,增强机体的抗隐球菌能力。
引文
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[2]吴成斯,余婷,刘琼琼.非HIV感染相关的隐球菌性脑膜炎97例临床特点及诊断分析[J].江西医药,2016,51(11):1220-1222.
[3]周静,陈钦开,杨柳,等.系统性红斑狼疮并发新型隐球菌脑膜炎的临床研究[J].江西医药,2011,46(5):438-440.
[4]谢小梅,许杨.抗真菌中药的作用机制研究进展[J].中国中药杂志,2004,29(3):2001.
[5]于军,苏学今,王丽.射干、金银花等八种中药抗真菌实验研究[J].军医进修学院学报,2007,28(4):2991.
[6]李建志,刘旭红,杨丽珍,等.11种中草药抗菌作用实验研究[J].中医药信息,2009,26(3):821.
[7]张文平,刘志春,刘建新,等.微量法测定肉桂醛、柠檬醛体外抗深部真菌活性[J].赣南医学院学报,2004,24(4):3641.
[8]官璀璀,郑乃刚,吴景兰,等.金银花对大鼠体内和体外RBL细胞的抗氧化保护作用及其机制[J].吉林大学学报:医学版,2009,35(6):1074-1078.
[9]王清,朱萱萱,张赤兵,等.金银花提取物抗菌作用的实验研究[J].中国医药导刊,2008,10(9):1428-1430.
[10]Butenko IG,Gladtchenko SV,Galushko SV.Anti-inflammatory properties and inhibition of leukotriene C4 biosynthesis in vitro by flavonoid baicalein from Scuetllaria baicalensis georgy roots[J].Agents Actions,1993,39:C49-51.
[11]Dou Yong-qing,Du Wen-li,Xue Yi,et al.The degrading effect of baicalin on bacterial endotoxin[J].Chin J Hosp Pharmacy,2005,25(7):683-685.(in Chinese)
[12]黄金玲,龙子江,吴华强,等.苓桂术甘汤对免疫功能低下模型小鼠淋巴细胞活性的影响[J].安徽中医学院学报,2004,23(1):40-43.
[13]宋宝辉,于新慧.黄芪对小鼠巨噬细胞、IL-2调节作用的影响[J].牡丹江医学院学报,2005,26(5):10-11.
[14]汪长中,程惠娟,官妍,等.苦参碱对体外白念珠菌生物膜抑制作用[J].中国公共卫生,2008,24(12):1491-1492.
[15]吴岚,周永梅,施琳俊,等.苦参碱对白色念珠菌黏附人口腔膜上皮细胞的影响[J].临床口腔医学杂志,2009,25(1):3-5.
[16]Mukherjee J,Nussbaum G,Scharff MD,et al.Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell[J].Exp Med 1995,181(1):405-409.
[17]Netski D,Kozel TR.Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by anticapsular monoclonal antibodies:importance of epitope specificity[J].Infect Immun,2002,70(6):2812-2819.
[18]Levitz SM,Dupont MP,Smail EH.Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans[J].Infect Immun,1994,62(1):94-202.
[19]Harrison TS,Kornfeld H,Levitz SM.11le effect of infection with human immunodeficiency virus on the antieryptoceccal aetivity of lymphocytes and monoeytes[J].Infect Dis,1995,172(3):665-671.
[20]Kawakami K,Qureshi MH,Koguchi Y,et al.Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by IL-12 and IL-18[J].Cell Immunol 1999,193(1):9-16.
[21]Zhang T,Kawakami K,Qureshi MH,et al.Interleukin-12(IL-12)and IL-18 synergistically induce the fungicidal activity ofmurine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells[J].Infect Immun,1997,65(9):3594-3599.
[22]Parayath KE,Harrison TS,Levitz SM.Effect of interleukin(IL)-15priming on IL-12 and interferon-gamma production by pathogenstimulated peripheral blood mononuclear cells from human immunode-ficiency virus-seropositive and-seronegative donors[J].J Infect Dis,2000,181(2):733-736.