益肾平喘合剂防治小鼠支气管哮喘的作用机理研究

目的:探讨医院制剂益肾平喘合剂防治小鼠支气管哮喘的作用机制。方法:采用卵白蛋白(OVA)腹腔注射致敏与雾化吸入激发制作哮喘模型,观察益肾平喘合剂对小鼠支气管的气道炎症、BALF上清液相关细胞因子(IFN-γ,IL-4)和血浆氧自由基的影响。结果:益肾平喘合剂的干预治疗能显著降低哮喘小鼠BALF中炎性细胞总数及EOS数量;BALF上清液中IFN-γ水平明显升高,IL-4水平显著下降;降低血浆中MDA含量,使得GPx、SOD的含量趋于正常。结论:益肾平喘合剂可能通过抑制气道炎症,调整Th1/Th2型细胞因子平衡,清除体内过多的氧自由基,从而起到防治哮喘的作用。     

小青龙汤对小鼠支气管哮喘模型气道炎症及细胞因子的影响

目的:探讨中药方剂小青龙汤对小鼠哮喘模型气道炎症及细胞因子的影响。方法:40只BALB/c小鼠随机分为正常对照组(A组)、哮喘模型组(B组)、小青龙汤低剂量组(C组)和小青龙汤高剂量组(D组)。B、C、D组采用卵蛋白(OVA)腹腔注射致敏与雾化吸入激发制作哮喘模型。于OVA激发结束后24h收集支气管肺泡灌洗液(BALF)计数炎性细胞总数及嗜酸性粒细胞(EOS)数目,并测定BALF上清液中白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)水平变化。结果:小青龙汤的干预治疗能显著降低小鼠BALF中炎性细胞总数及EOS数量;BALF上清液中IFN-γ水平明显升高,IL-4水平显著下降。D、C组与A组、B组有显著性差异(P<0.05),C组与D组结果亦存在显著性差异(P<0.05)。结论:小青龙汤能明显降低哮喘小鼠BALF中炎性细胞数量,影响细胞因子水平变化,从而改善哮喘气道炎症。     

补肾清肺方对小鼠支气管哮喘模型的影响

目的:探讨中药复方补肾清肺方对小鼠哮喘模型气道炎症及细胞因子的影响。方法:40只BALB/c小鼠随机分为正常对照组(A组)、哮喘模型组(B组)、补肾清肺方低剂量组(C组)和补肾清肺方高剂量组(D组)。B、C、D组采用卵蛋白(OVA)腹腔注射致敏与雾化吸入激发制作哮喘模型。于OVA激发结束后24h收集支气管肺泡灌洗液(BALF)计数炎性细胞总数及嗜酸性粒细胞(EOS)数目,并测定BALF上清液中白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)水平变化。结果:补肾清肺方的干预治疗能显著降低小鼠BALF中炎性细胞总数及EOS数量;BALF上清液中IFN-γ水平明显升高,IL-4水平显著下降。D、C组与A组、B组有显著性差异(P<0.05),C组与D组结果亦存在显著性差异(P<0.05)。结论:补肾清肺方能明显降低哮喘小鼠BALF中炎性细胞数量,影响细胞因子水平变化,从而改善哮喘气道炎症。     

过表达XB130抑制哮喘小鼠气道高反应性和气道炎症

目的:研究XB130在哮喘小鼠气道高反应(airway hyperresponsiveness,AHR)和气道炎症中的作用。方法:36只C57小鼠分为4组:正常对照组(Control,CON)、哮喘组(Asthma,AS)、腺病毒载体组(Ad-vector+AS)和腺病毒过表达XB130组(Ad-XB130+AS)。采用卵白蛋白(ovalbumin,OVA)建立小鼠过敏性哮喘模型,后两组小鼠分别尾静脉注射Ad-vector和Ad-XB130。最后一次雾化吸入后24小时进行气道高反应试验,收集支气管灌洗液(bronchi alveolar lavage fluids,BALF)。采用RT-PCR和Western blotting方法检测XB130表达。ELISA法检测血清中OVA特异性Ig E的含量。直接计数法计算BALF中嗜酸性粒细胞(eosinophile granulocyte,EOS)数量。ELISA方法用于检测BALF和肺组织中IL-4、IL-5、IL-13和IFN-γ的分泌。结果:哮喘小鼠肺组织中XB130表达减少,过表达XB130其m RNA和蛋白表达水平显著升高。过表达XB130降低醋甲胆碱(methacholine,Mch)诱导的气道高反应。与载体对照组(48±3)相比,XB130过表达(17±4)EOS数量显著减少。同时,过表达XB130(0.051±0.002)较载体对照组(0.128±0.007)Ig E含量减少。此外,XB130抑制哮喘小鼠中IL-4、IL-5和IL-13并促进IFN-γ分泌。结论:过表达XB130可抑制哮喘模型小鼠气道高反应性和炎症反应。     

卡介苗干预对哮喘小鼠肺组织IL-17A表达的影响及可能机制研究

目的:观察卡介苗干预对哮喘小鼠肺组织IL-17A的表达、气道炎症的影响,并探讨可能机制.方法:按随机数字表法,24只昆明小鼠分为正常对照(A组),模型组(B组),卡介苗(BCG)干预组(C组).C组小鼠每周一次皮内注射BCG 0.025 mg,连续3次.首次皮内注射4周后,第1、8、15天每只小鼠分别给予鸡卵清蛋白(OVA)与氢氧化铝混合腹腔注射,第22天给予1％ OVA溶液雾化吸入激发.激发后收集支气管肺泡灌洗液(BALF)行细胞总数及分类计数.肺组织HE染色行支气管粘膜下炎症评分.酶联免疫吸附试验法(ELISA)检测肺组织匀浆中的IL-17A和IFN-γ水平.结果:与正常对照组比较,BCG干预小鼠BALF中白细胞总数及中性粒细胞、嗜酸性粒细胞、淋巴细胞、巨噬细胞数均高于显著增高,低于模型组小鼠.BCG处理小鼠支气管粘膜下炎性细胞浸润程度较模型组小鼠明显降低(P＜0.01),比A组明显(P＜0.01).与对照组相比,模型组和BCG组小鼠肺组织匀浆中的IFN-γ显著相抵,在模型组小鼠更明显,IL-17A浓度增高,在模型组小鼠更明显(P＜0.05).结论:BCG干预可抑制气道炎症,可能通过上调Th1型免疫反应增加IFN-γ浓度、减少IL-17A在哮喘小鼠肺组织中表达,减少中性粒细胞的募集活化.     

婴儿型双歧杆菌对哮喘小鼠气道炎症的作用研究

目的探讨婴儿型双歧杆菌对气道过敏小鼠的气道炎症作用及其机制。方法 6周龄BALB/c雄性小鼠40只,随机分为4组:阴性对照组、哮喘组、婴儿型双歧杆菌预防组和婴儿型双歧杆菌治疗组。哮喘组、预防组和治疗组用卵清蛋白(Ovalbvmin,OVA)进行致敏和激发诱发哮喘,阴性对照组用生理盐水进行致敏和激发。预防组第0至14天灌胃菌液;治疗组第15至28天灌胃菌液;阴性对照组和哮喘组全程灌胃生理盐水作对照。观察小鼠气道过敏表现;计数肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中细胞总数评估气道炎症程度;肺组织行HE染色;ELISA法测定血清中IL-10、OVA特异性IgE和OVA特异性IgG1的浓度以及肺泡灌洗液中细胞因子IL-4、IL-5、IL-10、IL-13和IFN-γ的浓度。结果 (1)哮喘组小鼠在激发后出现搔抓口鼻、竖毛、打喷嚏、腹肌扇动、弓背直立、二便失禁以及体重下降等表现,预防组和治疗组的症状较轻。(2)预防组和治疗组BALF细胞数量明显低于哮喘组(P0.05)。(3)肺组织HE染色后,哮喘组小鼠肺组织出现明显的炎症细胞浸润,预防组和治疗组肺组织炎症明显减轻。(4)预防组和治疗组血清OVA特异性IgE浓度明显低于哮喘组(P0.05),并且预防组低于治疗组(P0.05);治疗组血清OVA特异性IgG1浓度明显低于哮喘组和预防组(P0.05);预防组和治疗组血清IL-10浓度明显高于哮喘组(P0.05),且治疗组高于预防组(P0.05);(5)预防组和治疗组肺泡灌洗液中IL-4、IL-13含量明显低于哮喘组(P0.05);IL-5、IL-10、IFN-γ各组浓度都较低,未测出有效浓度。结论口服婴儿型双歧杆菌可以减轻过敏症状,降低肺组织炎症浸润程度,抑制Th2免疫反应。     

特异性免疫治疗对屋尘螨致敏哮喘小鼠NKT细胞的影响

目的:研究特异性免疫治疗(SIT)对哮喘小鼠自然杀伤T(NKT)细胞的影响。方法:24只BALB/C小鼠随机分为对照组(A组)、哮喘模型组(B组)、哮喘免疫治疗(SIT)组(C组),各8只。通过屋尘螨提取液(HDM)诱导建立哮喘小鼠模型并进行SIT治疗。检测各组小鼠的气道反应性、支气管肺泡灌洗液(BAlF)细胞计数及分类、ELISA检测IL-4、IFN-γ以及应用流式细胞仪检测NKT细胞数目,通过RT-PCR方法检测T-bet和GATA-3mRNA表达水平;HE染色观察小鼠肺组织的改变。结果:与B组相比,C组气道反应性明显下降(P0.01);BALF中细胞总数及嗜酸性粒细胞(EOS)数显著减少(P0.01);血清IL-4分泌显著降低(P0.01),IFN-γ显著升高(P0.01);NKT细胞数及其成熟型比例明显升高(P0.05);T-betmRNA表达水平明显升高(P0.01),且与NKT细胞数及其成熟型比例呈正相关性,GATA-3mRNA表达水平明显降低(P0.05),且与NKT细胞数及其成熟型比例呈负相关性。B组肺部管腔周围炎性细胞聚集,组织上皮损伤,组织水肿,而C组肺部变应性炎症明显减轻。C组其他各项指标接近A组。结论:哮喘的发生可能与NKT细胞失调相关,通过改变NKT细胞数目及其成熟型比例来调节GATA-3/T-bet的表达可能是SIT治疗哮喘的作用机制之一。     

屋尘螨致敏/激发小鼠气道变态反应性炎症模型的构建

目的使用屋尘螨(HDM)提取液致敏和激发C57BL/6小鼠构建气道变态反应性炎症模型的方法。方法模型组和对照组,各8只。模型组以HDM致敏和激发小鼠,分别于第0、7、14、21天腹腔注射HDM,10 d后,连续雾化吸入HDM 3 d。对照组以PBS代替HDM。进行支气管肺泡灌洗液(BALF)细胞总数计数和分类计数,肺组织病理检查,ELISA测定BALF上清中IL-4、IL-5和IFNγ-水平。结果模型组可见明显炎性细胞浸润,以嗜酸性粒细胞为主。而对照组未见明显炎性细胞浸润。BALF中细胞总数计数和嗜酸性粒细胞比例较对照组明显升高(P<0.01);BALF上清中IL-4、IL-5水平较对照组明显升高(P<0.001),IFNγ-水平较对照组降低(P<0.01)。结论使用HDM致敏和激发C57BL/6小鼠成功地建立了小鼠气道变应性炎症模型。     

尘螨变应原Der f1植物表达产物诱导哮喘小鼠免疫耐受的研究

目的:采用尘螨变应原组分Der f1植物表达产物免疫治疗哮喘小鼠,了解其诱导哮喘小鼠免疫耐受的效果及机制.方法:将BALB/c小鼠分为正常组、哮喘组和治疗组,治疗组在致敏后分别给予尘螨变应原Der f1原核表达产物(rDE)和烟草叶片中的表达产物(rDP)免疫治疗,处死小鼠,取支气管肺泡灌洗液(BALF)、血清和肺组织,分别进行细胞学、螨特异性抗体、细胞因子和组织病理学检查,观察这些指标的变化.结果:哮喘组和治疗组BALF中细胞总数明显增多,中性和嗜酸性粒细胞超过50%;rDE和rDP治疗后,小鼠BALF中细胞总数和嗜酸性粒细胞减少;哮喘组和治疗组小鼠螨特异性IgE、IgG和IL-4水平升高,IFN-γ水平下降(P<0.01);rDE和rDP治疗后,IgE、IgG和IL-4水平下降,IFN-γ水平上升(P<0.01-0.05),以rDP疗效更好;哮喘组小鼠支气管、细支气管和小血管周围可见明显炎性细胞浸润,rDE和rDP治疗后,炎症减轻,以rDP改变更为明显.结论:尘螨变应原Der f1植物表述产物较原核表达产物能更有效地减轻螨性哮喘小鼠的气道炎症,诱导免疫耐受形成.     

HDAC8抑制剂PCI-34051对慢性支气管哮喘小鼠的治疗作用

目的探讨组蛋白去乙酰化酶8抑制剂PCI-34051对慢性哮喘小鼠气道炎症、气道重塑和气道高反应的治疗作用。方法 BALB/C小鼠分为正常组、哮喘组、地塞米松组和PCI-34051组。测定气道阻力,BALF细胞计数和分类计数,ELISA检测IL-4、IL-5、TGF-β1和IFN-γ。HE染色观察气道炎症,AB-PAS和Masson染色测定气道重塑。Western blot测定α-SMA和TGF-β1表达。结果与哮喘组比,地塞米松组和PCI-34051组气道阻力降低,BALF中炎性细胞总数和嗜酸性粒细胞减少,IL-4、IL-5、TGF-β1表达下降。地塞米松组和PCI-34051组HE染色气道周围炎症减轻,气道平滑肌增厚减弱;AB-PAS染色杯状细胞化生减轻;Masson染色面积减少。Western blot发现地塞米松组和PCI-34051组TGF-β1表达下降,但α-SMA降低不明显。结论 PCI-34051能够缓解慢性哮喘气道炎症、气道高反应和气道重塑。     

布地奈德通过干预线粒体钙单转运蛋白影响哮喘大鼠气道上皮细胞自噬和屏障功能的机制

摘要 目的：探究布地奈德通过干预线粒体钙单转运蛋白影响哮喘大鼠气道上皮细胞自噬和屏障功能的机制。方法：30只雄性SD大鼠作为研究对象,并根据实验目的分为3组：对照组（正常大鼠,生理盐水干预,n=10）,哮喘组（通过OVA诱导大鼠哮喘模型,n=10）,布地奈德组（气雾剂布地奈德用于治疗过敏性哮喘的大鼠,n=10）。通过钙测定试剂盒和蛋白印迹分析大鼠气道上皮细胞中Ca²⁺的吸收和MCU蛋白表达;TEER和TRITC 荧光分析检测大鼠气道上皮中的屏障功能;免疫组化分析分气道上皮细胞屏障功能相关因子ZO-1、E-cadherin的蛋白表达;ELISAF分析BALF上清液中炎性因子IL-4、IL-5和IL-13的水平;二氢乙锭衍生物和蛋白印迹分析BALF中ROS含量和caspase-3活性。结果：哮喘组较对照组Ca²⁺浓度降低,MCU蛋白表达升高（P<0.05）,布地奈德组较哮喘组Ca²⁺浓度升高,MCU蛋白表达降低（P<0.05）。哮喘组较对照组TEER降低,TRITC升高（P<0.05）,布地奈德组较哮喘组TEER升高,TRITC降低（P<0.05）。哮喘组较对照组ZO-1、E-cadherin的蛋白表达降低（P<0.05）,布地奈德组较哮喘组ZO-1、E-cadherin的蛋白表达升高（P<0.05）。哮喘组较对照组IL-4、IL-5和IL-13的水平升高（P<0.05）,布地奈德组较哮喘组IL-4、IL-5和IL-13的水平降低（P<0.05）。对照组组支气管和肺泡结构未见异常,与对照组相比哮喘组大鼠表现出肺泡间隔增厚,可见的肺毛细血管水肿,以及肺毛细血管和肺泡间隙中的大量炎性细胞浸润（P<0.05）,与哮喘组相比,布地奈德组显著减轻肺部病变的严重程度（P<0.05）。哮喘组较对照组LC3B II/I、ATG5、Beclin-1 和LC3II 的表达升高（P<0.05）,布地奈德组较哮喘组LC3B II/I、ATG5、Beclin-1 和LC3II 的表达降低（P<0.05）。哮喘组较对照组ROS含量和caspase-3活性升高（P<0.05）,布地奈德组较哮喘组ROS含量和caspase-3活性降低（P<0.05）。结论：布地奈德通过调节MCU表达介导气道上皮细胞的屏障完整性和自噬水平,缓解哮喘气道炎症,改善哮喘症状。     

Effects of catalpol on bronchial asthma and its relationship with cytokines

An animal (BALB/c mice) model of catalpol associated with bronchial asthma in vivo was established, and the effects of catalpol and its relationship with cytokines were investigated. A total of 30 adult BALB/c mice were randomly divided into a positive control group, a model group, and a catalpol group, with 10 mice in each group. The lung function of mice, the cell count, and the cytokine concentrations in bronchoalveolar lavage fluid (BALF) were detected. The levels of cytokines [interleukin 4 (IL-4), interleukin 5 (IL5), and interferon gamma (IFN-γ)] in BALF were measured with enzyme-linked immunosorbent assay methods. The total number of cells in the BALF of the group treated with catalpol was significantly lower than the model group. After treatment with catalpol, the eosinophils and neutrophils of the mice were remarkably reduced compared with the model group. The malondialdehyde content in the lung tissue homogenate of the mice was also decreased in the catalpol group. The cytokines IL-5 and IL-4 exhibited a similar tendency: the concentrations of IL-4 and IL-5 for the catalpol group were dramatically decreased compared with the model group. However, the IFN-γ concentration for the catalpol group was higher than the model group. The results indicated that IL-5 may involve in the pathologic process of asthma-like IL-4, and an inflammatory reaction may still exist in the airway during the remission stage of asthma. The imbalances of the cytokine network might be an important molecular basis in the asthma pathogenesis. It is suggested that catalpol may be a potential drug for the clinical treatment of asthma.     

Th 细胞因子IL-17、IFN-γ、IL-4 在狼疮性肾炎中的表达及意义

目的:探讨T辅助细胞(Th)相关细胞因子在狼疮性肾炎发病中的免疫机制作用。方法:64例系统性红斑狼疮患者和28例健康体检者作为对照,采用酶联免疫吸附测定法(ELISA法)检测所有受试者血清IL-17、IFN-γ、IL-4水平,并对其与SLEDAI、SDI、24小时尿蛋白量相关性进行研究。结果:狼疮性肾炎组血清IL-17水平显著高于狼疮无肾炎组和健康对照组(P<0.001),狼疮性肾炎组血清IFN-γ水平显著高于狼疮无肾炎组(P<0.05)和健康对照组(P<0.01),血清IL-4水平在狼疮性肾炎组、狼疮无肾炎组均显著高于健康对照组(P<0.01)。狼疮性肾炎组IFN-γ/IL-4比值显著高于狼疮无肾炎组(P<0.01)和健康对照组(P<0.05);狼疮无肾炎组IFN-γ/IL-4比值显著低于健康对照组(P<0.01)。SLE患者血清IFN-γ表达水平与SLEDAI积分呈正相关(r=0.402,P<0.05),血清IL-17、IL-4表达水平与SLEDAI、SDI、抗ds-DNA抗体、C3、24小时尿蛋白量均无相关性。结论:狼疮性肾炎患者外周血中IL-17、IFN-γ、IL-4等促炎细胞因子均有不同程度升高促起炎症发生及组织损伤,参与了狼疮性肾炎的免疫发病过程。     

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。     

Extracts of Coleus forskohlii relieves cough and asthma symptoms via modulating inflammation and the extracellular matrix

Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.     

妊娠期肝内胆汁淤积症患者外周血中维生素D受体 与Th1/Th2 型细胞因子的变化

目的:研究妊娠期肝内胆汁淤积症患者外周血中维生素D受体的表达与Th1/Th2型细胞因子干扰素-γ/白细胞介素-4(IFN-γ/IL-4)的变化关系,探讨ICP发病机制。方法:选取ICP患者31例(ICP组),孕周相匹配的正常孕妇31例(正常对照组)。采用酶联免疫吸附试验(ELISA法),检测两组孕妇血清中Th1型细胞因子(IFN-γ)和Th2型细胞因子(IL-4)的水平;采用实时荧光定量逆转录-多聚酶链反应(qRT-PCR),检测两组孕妇外周血单个核细胞维生素D受体(VDR)mRNA的表达水平,采用3-磷酸甘油醛脱氢酶(GAPDH)为内参,根据相对定量公式:2-△△CT分析VDR mRNA的表达水平。结果:(1)ICP组外周血清中IFN-γ的浓度[(230.93±36.04)pg/ml]明显高于正常对照组[(138.37±25.08)pg/ml],差异有统计学意义(P<0.01)。ICP组血清中IL-4浓度[(9.99±3.19)pg/ml]和正常对照组[(8.58±2.43)pg/ml]比较,差异无统计学意义(P>0.05)。ICP组IFN-γ/IL-4比值(24.56±6.91)高于正常对照组(17.13±4.84),差异有统计学意义(P<0.05)。(2)ICP组外周血单个核细胞维生素D受体mRNA的表达明显低于正常对照组(P<0.01),正常对照组VDR的表达定义为1.0,ICP组的表达量为0.4。(3)ICP组外周血中VDR的表达水平与IFN-γ浓度呈明显负相关(r=-0.833,P<0.01),与IL-4浓度无明显相关(r=-0.109,P>0.05),与IFN-γ/IL-4比值呈负相关,但相关性不强(r=-0.356,P=0.049<0.05)。结论:ICP患者外周血Th1/Th2型细胞因子平衡由Th2向Th1偏移,可能与ICP孕妇外周血单个核细胞VDR的表达减少有关。     

T helper cells subtypes and their cytokine gene expression affected by carvacrol in sensitized mice administered during sensitization period

Th1, Th2, Th17, and Treg cells and their cytokine gene expressions in splenocytes of control mice, ovalbumin sensitized (S), and S treated with dexamethasone and carvacrol during a sensitization period were examined. Th2 and Th17 population as well as the gene expression of IL-4, IL-17, and TGF-β were increased, but Th1, Th1/Th2 ratio, the gene expression of IFN-γ and FOXP3 as well as the IFN-γ/IL-4 ratio were decreased in S compared with control group ( P < 0.001 for all cases). Carvacrol treatment caused significant reduction of Th2 and Th17 population as well as gene expression of IL-4, IL-17, and TGF-β but increase in Treg cells, Th1/Th2 ratio, gene expressions of FOXP3, IFN-γ, and IFN-γ/IL-4 ratio ( P < 0.05 to P < 0.001). The population of Th1, Th2, Th17 cells as well as the gene expression of IL-4, IL-17, and TGF-β were significantly decreased, but only Treg was increased in the dexamethasone treatment group ( P < 0.05 to P < 0.001). Carvacrol treatment during the sensitization period showed a more specific effect on Th1/Th2 imbalance in sensitized mice than dexamethasone, which may indicate the therapeutic potentials of carvacrol in disorders associated with Th1/Th2 imbalance such as asthma.     

2009流行性感冒患者血清细胞因子的变化特点

本文旨在通过比较30例2009甲型H1N1流行性感冒(简称流感)患者经奥司他韦治疗前、后血清中细胞因子的变化特点,探讨其可能的发病机制.30例患者分为奥司他韦治疗前组和治疗后组,另选取健康志愿者20例为对照组.采用酶联免疫吸附试验,检测患者血清白细胞介素10(IL-10)、IL-2、IL-8及γ干扰素(IFN-γ)水平...     

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

The present study aims to investigate the association between the genetic polymorphisms of interferon (IFN)-γ and interleukin (IL)-4 with childhood susceptibility to asthma and the levels of IFN-γ, IL-4, and immunoglobulin (Ig) E among asthmatic children. A total of 100 asthmatic children and 122 control children were enrolled in the present study. The genotypes of the IFN-γ gene at the − 179G/T locus and the IL-4 gene at the − 33C/T and − 589C/T loci were detected using polymerase chain reaction with restriction fragment length polymorphism. The IFN-γ gene at the + 874A/T locus and the IFN-γ CA repeats were tested using allele-specific and capillary electrophoresis, respectively, whereas the IFN-γ, IL-4, and total IgE levels were measured using enzyme-linked immunosorbent assays. The 100 asthmatic children and the 122 control children were all GG homozygous in the − 179 locus of the IFN-γ gene, which shows that the IFN-γ gene is not mutated at the − 179 locus. No significant differences were found in terms of genotypic and allelic frequency distribution in the IFN-γ gene or the CA repeat at the + 874A/T locus between the asthmatic children and the control (P > 0.05). An association was found between the polymorphism of the IFN-γ gene at + 874A/T and IFN-γ levels. IFN-γ expression was lower among patients with the AA genotype than those with the AT genotype (P < 0.05); the genotypic and allelic frequency distributions of the IL-4 gene at − 33C/T and − 589C/T were significantly different between the asthmatic children and the control (P < 0.05). The levels of IL-4 and IgE among children with TT genotype at the − 33 and − 589 loci were higher than those with the CT genotype, but only the polymorphism at − 33C/T was associated with IL-4 levels (P < 0.05). The polymorphisms of the IFN-γ gene at + 874A/T or the CA repeats are not correlated with susceptibility to asthma. Thus, the polymorphism at + 874A/T is correlated with IFN-γ level. The TT genotypes of the IL-4 gene at the − 33 and − 589 loci are associated with asthma susceptibility in children, and polymorphism at the − 33 locus may be associated with IL-4 level.