蛋氨酸脑啡肽（MEK）联合干扰素γ抗肿瘤作用研究

观察蛋氨酸脑啡肽（MEK）和注射用重组人干扰素γ（IFN-γ）单独和联合应用的抗肿瘤效应。应用动物移植性肿瘤的体内试验法,分别观察MEK、IFN-γ和MEK＋IFN-γ对肿瘤的抑瘤作用及小鼠生命延长率情况。结果显示,MEK组、IFN-γ组和MEK＋IFN-γ组的抑瘤作用分别为129．11％（P〈0．001）、78．11％（P〈0．001）、231．10％（P〈0．001）,均有显著差异;生命延长率MEK组20．28％（P〈0．001）有显著差异,IFN-γ组13．50％（P〉0．001）无显著差异,MEK＋IFN-γ组41．25％（P〈0.001）有显著差异。可见,MEK、IFN-γ和MEK＋IFN-γ都对小鼠移植性瘤有一定的抑制作用,MEK和MEK＋IFN-γ能够延长小鼠生命,而IFN-γ单独应用不能延长小鼠生命。MEK和IFN-γ联合应用时作用相加。而不良反应未相加。     

扶正化积方对H22肝癌荷瘤小鼠化疗的增效减毒作用

目的:研究扶正化积方对H22荷瘤小鼠化疗的增效减毒作用。方法:建立小鼠皮下H22移植性肝癌模型,随机分为4组:模型对照组、FZHJF组(40.95g/kg)、5-氟尿嘧啶组(5-FU)(0.2 m L/10g)和联合给药组(FZHJF+5-FU),连续给药12 d后,采集肿瘤与脏器称重并计算抑瘤率、肝脏指数、脾脏指数和胸腺指数;并对各组肿瘤外观和肿瘤病理进行分析。结果:肿瘤病理结果显示均为典型的肝细胞癌。与模型对照组比较,其余三组瘤重均显著减小(P0.05);而联合用药组的瘤重显著小于5-FU组和FZHJF组(P0.05),肿瘤外观图也显示联合给药组瘤块小于FZHJF组和5-FU组。扶正化积方单独使用的抑瘤率为40.5%,联合5-FU后,抑瘤率达到66.7%,大于两者合并用药后的理论相加效应值65.6%;与5-FU组比较,FZHJF组与联合用药组的体质量显著增加(P0.05),FZHJF组与联合用药组的胸腺指数与脾脏指数均显著高于模型对照组和5-FU组(P0.05)。结论:扶正化积方对H22肝癌荷瘤小鼠的化疗具有增效和减毒双重作用。     

秀珍菇粉对H22荷瘤小鼠体内抗肿瘤作用研究

目的本试验旨在研究秀珍菇抗肿瘤作用及其抑瘤机制。方法选用ICR雄性小鼠60只,取10只作为空白组,剩余50只小鼠通过腋部皮下接种H22小鼠腹水构建荷瘤小鼠模型,造模后随机分为模型组、阳性药(CTX)组、秀珍菇低、中、高剂量组,每组10只。模型组小鼠灌服生理盐水,阳性药组小鼠按20 mg/kg体重隔天腹腔注射注射环磷酰胺(CTX)生理盐水溶液,秀珍菇低、中、高剂量组小鼠分别按750、1500、3000 mg/kg体重每天剂量灌服秀珍菇生理盐水混悬液。给药10 d后,测定各组小鼠平均瘤重,肿瘤抑制率;测定免疫器官脏器指数、血清免疫球蛋白和细胞因子含量;测定肝、肾抗氧化指标;观察肿瘤和脾组织HE染色病理切片。结果 (1) CTX及秀珍菇低、中、高剂量组小鼠的平均瘤重均极显著低于模型组(P0. 01),四组小鼠肿瘤抑制率分别为55. 18%,29. 06%、47. 47%和48. 80%。(2)与空白组比较,模型组小鼠脾指数、血清Ig A和TNF-α含量及肝MDA含量显著升高(P0. 05,P0. 01),血清IL-6含量有上升趋势(P 0. 05),而血清IL-2含量、肝CAT和GSH-Px活性及肾SOD、GSH-Px和CAT活性显著降低(P0. 05,P0. 01);同时,CTX组小鼠胸腺指数显著低于空白组(P0. 05)。(3)秀珍菇对荷瘤小鼠免疫和抗氧化功能异常改变具有逆转作用:与模型组比较,秀珍菇各剂量组小鼠血清Ig A和TNF-α含量及高剂量组小鼠IL-6水平显著降低(P 0. 05,P 0. 01),低剂量组小鼠血清IL-2水平显著升高(P 0. 01);秀珍菇处理还显著提高了各剂量组荷瘤小鼠肝CAT活性及肾SOD和CAT活性(P 0. 05,P 0. 01),显著升高中、高剂量组肝GSH-Px活性和低、中剂量组肾GSH-Px活性(P 0. 05,P 0. 01),并显著降低中剂量组的肝MDA含量(P 0. 05)。(4)与CTX组比较,秀珍菇高剂量组小鼠脾指数显著提高(P 0. 05),而血清IL-6水平显著降低(P 0. 05)。(5)肿瘤组织病理切片显示CTX组和秀珍菇各剂量组的肿瘤坏死面积明显增加。结论秀珍菇可抑制H22实体移植瘤生长,其机制与其具有较强的免疫调节和抗氧化作用有关。     

PVAX-MAGE-1基因疫苗延缓小鼠肝癌细胞H22腹水瘤和实体瘤的生长

为观察重组基因疫苗PVAX-MAGE-1的抑瘤效应,构建黑色素瘤抗原-1(melanoma antigen-1,MAGE-1)真核基因表达载体--PVAX-MAGE-1.以重组质粒免疫C57BL/6小鼠后,ELISA法检测表明,与对照鼠(PVAX-1和生理盐水注射小鼠)比较,免疫小鼠脾淋巴细胞上清液中的细胞因子IL-2和IFN-γ明显升高(P0.05);淋巴细胞-肿瘤细胞混合培养证明,免疫小鼠外周血CD8+T细胞对靶细胞的特异性杀伤作用明显增强(P0.05).体内实验证明,PVAX-MAGE-1免疫C57BL/6小鼠,可显著延缓移植性H22腹水瘤及实体瘤在小鼠体内的生长.实验结果提示,重组基因疫苗PVAX-MAGE-1有明显的延缓肿瘤生长的作用,其抑瘤作用与提高T淋巴细胞IL和IFN表达,增强对肿瘤杀伤作用直接相关.     

CpG寡核苷酸联合热固化瘤苗对肝癌细胞Hca-F荷瘤小鼠的免疫治疗研究

目的探讨CpG寡核苷酸(ODN)联合热固化瘤苗的抗肿瘤作用。方法剥取肿瘤．称重并计算抑瘤率;MTT法测免疫小鼠CTL、Mψ和CTL细胞的体外杀伤活性;ELISA法测免疫小鼠血清中IL-10、IL-12水平。结果联合使用CpG ODN和热固化瘤苗可以诱导荷瘤小鼠的抑瘤作用,其抑瘤率与单独使用瘤苗或CpG ODN比较差异有显著性;联合使用CpG ODN和热固化瘤苗可以提高荷瘤小鼠NK、Mψ和CTL细胞的体外杀伤活性,与单独使用瘤苗组相比较,差异具有显著性,但与单独使用CpG ODN组相比较,NK、Mψ细胞的体外杀伤活性差异无显著性;联合使用CpG ODN和热固化瘤苗可以提高荷瘤小鼠血清中IL-12水平并降低血清中IL-10水平,与二者单独使用组比较差异都具有显著性。结论联合使用CpG ODN和热固化瘤苗能显著提高机体的免疫功能,尤其是特异性细胞免疫功能。     

N-CWS灌胃对小鼠移植性肿瘤及免疫功能的影响

为了考察红色诺卡氏菌细胞壁骨架(Nocardia rubra cell wall skeleton,N-CWS)灌胃给药对小鼠的体内抑瘤效应及其免疫调节作用,采用小鼠肉瘤S_(180)的移植性肿瘤模型,检测N-CWS灌胃给药的抑瘤活性;同时观察N-CWS体内细胞毒作用和对正常小鼠的毒性、免疫器官重量、巨噬细胞(MΦ)吞噬功能及脾淋巴细胞转化的影响.结果显示,小鼠灌服N-CWS的LD_(50)＞1.2 g/kg;N-CWS 200、400、800 mg/kg剂量灌胃小鼠对S_(180)有明显的抑制作用,其抑瘤率分别为63.33%、71.11%、64.88%;与对照组比较,N-CWS可增加免疫器官重量和提升外周血白细胞数量、能明显提高小鼠MΦ的吞噬活性及显著提高淋巴细胞转化率(P＜0.05),同时N-CWS激活了的MΦ对肿瘤细胞的细胞毒效应亦明显增强(P＜0.05).因此N-CWS适用于口服给药,对小鼠移植性肿瘤有明显的抑制作用,其抗肿瘤作用可能与增强机体免疫功能有关.     

凤丹籽油对小鼠H22肿瘤的抑制作用

探讨凤丹籽油对小鼠移植性肿瘤H22的抑瘤作用及机制。建立肝癌H22移植性肿瘤模型小鼠,随机分为正常组、模型组、5-氟尿嘧啶(5-FU)阳性对照组、凤丹籽油高、中、低剂量组,给药10 d后处死。结果表明:低、中、高剂量组的抑瘤率分别是18.4%、26.9%、34.7%,具有较好量效关系。与模型组相比,低、中、高剂量组能不同程度提高胸腺、脾脏指数,降低AST、ALT、ALP,增加WBC;降低TE活性和BCL-2表达,显著提高BAX表达。以上结果表明,高剂量凤丹籽油对H22荷瘤小鼠有明显的抑瘤作用,其机制可能是通过调节免疫功能和抑制TE活性、BCL-2表达,提高BAX表达而发挥肿瘤抑制作用。     

细胞因子与抗肿瘤药物体外协同抑制宫颈癌细胞的敏感性试验

目的探讨3种细胞因子单一、协同以及与化疗药物顺铂(DDP)的联合作用杀伤宫颈癌Hela细胞株的影响。方法应用四甲基偶氮唑盐比色法(MTT比色法)、检测与化疗药物DDP单独或联合应用组及药物作用的12 h与24 h的吸光度值(A),计算杀伤率。台盼蓝拒染计算杀伤率对照。结果单独应用3种细胞因子时,IFN-α(干扰素-α)、TNF-α(肿瘤坏死因子)对宫颈癌Hela有细胞毒作用,IL-2对宫颈癌Hela细胞株则细胞毒作用不明显。IFN-α、IL-2、TNF-α可以增强DDP的抑瘤作用,与DDP单独作用差异具有显著性(P<0.01)。IFN-α、IL-2(白细胞介素-2)、TNF-α联合作用具有协同作用,均与单一应用差异具有显著性(P<0.01)。细胞因子均可以增强DDP的抑瘤作用并与其作用的先后及时间具有依赖关系。结论MTT比色法为临床肿瘤化疗的药物敏感性检测提供了简便、快速的方法[1]。不同类型的肿瘤有着不同的药敏谱。IFN-α、TNF-α、IL-2与DDP联合具有协同作用,为宫颈癌患者化疗提供了理想的参考方案。     

重组别藻蓝蛋(rAPC)抑瘤活性及其对免疫作用的研究

目的:观察重组别藻蓝蛋白(rAPC)对接种H22肝癌细胞小鼠的抑瘤活性及其免疫作用.方法:昆明小鼠随机分为5组(10只/组),即模型组、rAPC低、中、高剂量组(25,50,100mg/kg·d)、环磷酰胺组(CY对照组).建立小鼠肝癌1422移植瘤模型,次日除模型组外,其余4组分别以不同剂量的rAPe、CY灌胃,于15d后处死,完整剥离出肿瘤、胸腺、脾脏,准确称重,计算抑瘤率、胸腺指数和脾指数,并采用放免法(PIA)测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平.结果:rAPC低剂量组小鼠H22肿瘤质量增长较模型组缓慢(P＜0.05),中、高剂量组较模型组显著缓慢(P＜0.01),抑瘤率分别为25.2%、36.7%、43.1%;rAPC各剂量组能升高胸腺指数、脾指数和血清中细胞因子IL-6、TNF-α的水平.结论:rAPC可有效抑制H22肝癌的生长,促进小鼠胸腺和脾脏的生长发育,提高小鼠的免疫功能,从而抑制肿瘤的生长.     

灵芝多糖GLP 抑制小鼠骨肉瘤细胞S-180 在体内生长的作用机制

目的:探讨灵芝多糖成分(GLP)抑制肿瘤的作用机制。方法:在小鼠右腋皮下接种1×106TC-1细胞后7天后,用100mg/kg、200mg/kg和400mg/kg 3种剂量给小鼠口服灌胃给药20天,然后观察肿瘤的重量,并用ELISA检测小鼠血清中IL-2、IL-6和TNF-alpha,用流式细胞仪检测其外周血中CD4+和CD8+。结果:100mg/kg、200mg/kg和400mg/kg 3种剂量给小鼠口服灌胃给药20天,与对照组比较,抑瘤率分别可以达到53%、59%和58%,P<0.05;小鼠外周血血清中的IL-2从1.27ng/mL提高到了2.88ng/mL,P<0.05;TNF-α从1.05ng/mL提高到了1.82ng/mL,P<0.05;而IL-6则没有明显的变化。CD4+细胞水平升高(从54.80%提高到了58.27%),但差异无统计学意义(P>0.05);CD8+细胞明显增多(从24.15%提高到了45.36%),差异有统计学意义(P<0.05)。结论:GLP有明显抑瘤作用,但抑瘤作用与GLP剂量不存在依赖关系。GLP对肿瘤细胞生长的抑制是通过提高小鼠的细胞免疫能力来实现,而并非直接杀伤肿瘤细胞。     

Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat middle cerebral arteries

Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10 microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P < 0.001). At these concentrations, PD98059 also significantly reduced the vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These results demonstrate that pressure-induced myogenic tone is inhibited by PD98059 at the concentrations that have been reported to be selective for inhibition of MEK and the MAP kinase cascade. However, our results also demonstrate that PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular smooth muscle.     

Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling

Interleukin-11 (IL-11) displays epithelial cytoprotective effects during intestinal injury. Antiapoptotic effects of IL-11 have been described, yet mechanisms remain unclear. Fas/CD95 death receptor signaling is upregulated in ulcerative colitis, leading to mucosal breakdown. We hypothesized that IL-11 inhibits Fas ligand (FasL)-mediated apoptosis in intestinal epithelia. Cell death was monitored in IEC-18 cells by microscopy, caspase and poly(ADP-ribose) polymerase cleavage, mitochondrial release of cytochrome c, and abundance of cytoplasmic oligonucleosomal DNA. RT-PCR was used to monitor Fas, cIAP1, cIAP2, XIAP, cFLIP, survivin, and Bcl-2 family members. Fas membrane expression was detected by immunoblot. Inhibitors of JAK2, phosphatidylinositol 3-kinase (PI3-kinase), Akt 1, MEK1 and MEK2, and p38 MAPK were used to delineate IL-11's antiapoptotic mechanisms. IL-11 did not alter Fas expression. Pretreatment with IL-11 for 24 h before FasL reduced cytoplasmic oligonucleosomal DNA by 63.2%. IL-11 also attenuated caspase-3, caspase-9, and poly(ADP-ribose) polymerase cleavage without affecting expression of activated caspase-8 p20 or cytochrome c release. IL-11 did not affect mRNA expression of the candidate antiapoptotic genes. The MEK1 and MEK2 inhibitors U-0126 and PD-98059 significantly attenuated the protection of IL-11 against caspase-3 and caspase-9 cleavage and cytoplasmic oligonucleosomal DNA accumulation. Although Akt inhibition reversed IL-11-mediated effects on caspase cleavage, it did not reverse the protective effects of IL-11 by DNA ELISA. We conclude that IL-11-dependent MEK1 and MEK2 signaling inhibits FasL-induced apoptosis. The lack of reversal of the IL-11 effect on DNA cleavage by Akt inhibition, despite antagonism of caspase cleavage, suggests that IL-11 inhibits caspase-independent cell death signaling by FasL in a MEK-dependent manner.     

LIG抗炎,解热活性的研究

本文研究了当归提取物LIG的抗炎,解热活性.研究发现LIG(2.5,5,10 mg/kg)对角叉菜和右旋糖苷诱导的足肿胀的抑制率分别为22.2%,49.4%,76.5%和20.8%,44.2%,75.3%(P＜0.001);对棉球肉芽肿的抑制率为29.2%,44.9%,58.8%(P＜O.001);对小鼠白细胞迁移的抑制率为20.7%,35.6%,48.2%(P＜0.001).此外,LIG可降低啤酒酵母导致的高热(P＜0.001).并且,LIG的抗炎,解热作用均成剂量依赖性.以上结果显示LIG具有非常强的抗炎,解热活性.     

金黄色葡萄球菌肠毒素A对H22小鼠移植瘤的抑制作用

旨在探讨金黄色葡萄球菌肠毒素A(SEA)在KM鼠体内的抑瘤效果.建立H22荷瘤小鼠模型,将20只小鼠随机分为对照组(生理盐水)、低剂量组(15 μg/ml)、中剂量组(25 μg/ml)和高剂量组(50 μg/ml),观察肿瘤生长趋势,计算抑瘤率,通过ELISA检测IL-2的含量.结果显示,给药组肿瘤生长趋势均较对照组缓慢;对照组、低剂量组、中剂量组、高剂量组的抑瘤率分别为0,28.9%,34.0%,51.0%(P<0.05);血清中IL-2含量分别为58.9 pg/ml、83.6 pg/ml、91.8 pg/ml、118.1 pg/ml.金黄色葡萄球菌肠毒素A(SEA)可抑制H22肿瘤的生长,并上调IL-2的分泌.     

Interleukin-12 prevents diaphragm muscle deterioration in a septic animal model

The effects of an intravenous injection of Interleukin-12 (IL-12) after endotoxin administration and without endotoxin administration on diaphragm muscle were studied using Wistar rats. Three treatment groups, namely a control (Saline+endotoxin) group, an IL-12+endotoxin group and an IL-12 only group were studied. E. coli endotoxin (30 mg/kg) was injected intraperitoneally 5 min after Saline or IL-12 (0.25 microg) injection. In the control group, the force-frequency curves, twitch tension (TT) and slope during contraction time (TT/CT) were significantly lower at 4 h than those at 0 h due to endotoxin (P<0.001, P<0.01 and P<0.01, respectively), and NO production was increased at 4 h as shown by NADPH diaphorase staining. In the IL-12+endotoxin group, the decrement of the force-frequency curves, TT and TT/CT induced by endotoxin at 4 h were significantly prevented compared with those of the control group (P<0.001, P<0.05 and P<0.05, respectively), and NO production was blocked at 4 h. In the IL-12 only group, the force-frequency curves were decreased in the range of high frequency and IL-12 resulted in NO production. Furthermore, the positive muscle fibers detected by NADPH diaphorase staining were classified as type I and IIa muscle fibers by ATPase staining in the control and IL-12 only groups. It is concluded that IL-12 prevents the deterioration of diaphragm muscle contraction induced by endotoxin by reducing NO production in type I and IIa muscle fibers. These results suggest that IL-12 and endotoxin may interfere with each other.     

Differential regulation of IL-1beta and TNF-alpha RNA expression by MEK1 inhibitor after focal cerebral ischemia in mice

Activation of the extracellular-signal-responsive kinase (ERK 1/2) by MAP kinase/ERK kinase (MEK1/2) following ischemia/reperfusion in the brain has been associated with cell death since inhibition of MEK1/2 provides neuroprotection in cerebral ischemia injury. Since inflammation has been implicated in ischemic brain injury, the present study investigated whether MEK1/2 modifies expression of two key inflammatory cytokines, IL-1beta and TNFalpha, that have been shown to exacerbate ischemic brain injury. A mouse model of transient cerebral ischemia was deployed to test the effect of selective MEK1/2 inhibitor (SL327) on infarct size and cytokine expression. SL327 (100 mg/kg, i.p.) administered 15 min prior to ischemia resulted in 64% reduction in infarct size over controls (n = 8, P < 0.01). Under the same condition, SL327 significantly reduced peak expression of IL-1beta mRNA (59% reduction compared to vehicle, P < 0.01, n = 4) but not TNF-alpha mRNA. A parallel reduction in IL-1beta protein (67%, P < 0.05, n = 6) was also observed using ELISA analysis. These data suggest that the neuroprotective effect of MEK1/2 inhibition may be mediated by suppression of IL-1beta. The study also demonstrates for the first time that these two cytokines are differentially regulated by kinase mediated signaling pathways.     

Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cells

Endogenous cardiotonic steroids (ECS) are putative ligands of the inhibitory binding site of the membrane sodium pump (Na+, K+-ATPase). There is growing evidence that cardiotonic steroids may promote the growth of cardiac and vascular myocytes, including evidence indicating growth stimulation at concentrations in the same range as circulating ECS concentrations. We investigated four parameters to determine whether ouabain, a proposed ECS, promotes growth of immortalized rat proximal tubule epithelial cells: cell count by hemocytometer; metabolic activity as reflected in the mitochondrial conversion of the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, to its formazan product (MA); DNA synthesis reflected as bromodeoxyuridine incorporation (DNA); and mitosis reflected as histone phosphorylation state detected using anti-phosphohistone 3 antibody (HP). Maximum stimulatory responses were observed at 1 nm ouabain (MA, 20.3% increase, p < 0.01; DNA, 28.4% increase, p < 0.001; HP, maximum response at 0.5 h, 50% increase, p < 0.001). We observed that growth stimulation was associated with stimulation of ERK1/2 phosphorylation (ERK-P), and both growth and ERK-P could be blocked by the MEK inhibitor (U0126, 100 nm). Western blot analysis revealed that the only alpha isoform of Na+, K+-ATPase that could be detected in these cultures was the highly ouabain-resistant alpha1 isoform. Measurement of ouabain inhibition of ion transport in these cultures using 86Rb+ uptake revealed the predominance of the expected ouabain-resistant isoform (IC50 = 24 microm) and an additional minor ( approximately 15%) ouabain-sensitive inhibition with IC50 approximately 30 pm. Similar bimodal transport inhibition curves were obtained in freshly dissected rat proximal tubules. These results indicate that renal epithelial cells may be a sensitive target of the ERK1/2-activating and growth-promoting effects of ouabain even in the presence of ouabain-resistant Na+, K+-ATPase.     

长效干扰素对CHB患者CD4^＋T细胞ICOS表达及血清IFN-γ、IL-4水平的影响

目的探讨长效干扰素对慢性乙型肝炎患者外周血CD4^＋T细胞上ICOS表达及血清IFN-γ、IL-4水平的影响。方法慢性乙型肝炎患者52例,其中聚乙二醇干扰素α2a治疗28例,常规治疗24例,另征集健康志愿者20例为正常对照组。采集治疗前及治疗后24、48周的患者外周血,以FCM检测ICOS^＋CD4^＋T细胞在PBMC中的频数变化;以ELISA检测治疗前后患者血清中IFN-γ、IL-4的水平变化;以Realtime—PCR检测患者HBV—DNA载量变化。结果慢性乙肝患者CD4^＋T细胞ICOS表达水平明显高于正常对照者（P〈0．001）,干扰素治疗者48周时ICOS表达水平低于常规治疗者,差异有统计学意义（P〈0．01）。经干扰素治疗后,患者Th1细胞因子IFN-γ水平升高,与常规治疗者相比有差异有统计学意义（P〈0．001）;而Th2细胞因子IL-4水平逐渐降低,与常规治疗者相比差异有统计学意义（P〈0．001）。干扰素治疗者ICOS、HBV-DNA载量变化值同IFN-γ水平的变化值呈负相关（P〈0．001）,而与IL4水平的变化值则为正相关（P〈0．001）。结论慢性乙肝患者存在着细胞免疫紊乱,干扰素治疗可以在一定程度纠正患者体内的Th2偏移,降低CD4^＋T细胞上ICOS的表达,促进IFN-γ表达,发挥抗病毒作用。