Orai1在载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成中的表达

目的探讨Orai1在载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化斑块形成过程中的表达。方法选取7~8周龄雄性Apo E-/-小鼠及野生型C57BL/6J小鼠,高脂饲喂20、27和33周后,在各个时点处死动物。取主动脉制备连续切片,HE、Masson染色计算机图像分析仪测定斑块面积占管腔面积百分比,及胶原成分占斑块面积百分比;油红O染色分析斑块中脂质含量;免疫组织化学染色测定平滑肌细胞阳性表达Orai1的百分比;Western Blot定量分析Orai1在易损斑块形成过程中的动态表达。结果与同周龄C57BL/6J小鼠相比,Apo E-/-小鼠主动脉Orai1表达增高,且随着其周龄增加,Orai1在Apo E-/-小鼠主动脉的表达动态升高(P0.05)。结论 Orai1参与动脉粥样硬化斑块形成的病理过程,在其形成过程中其表达上调。     

普伐他汀预防载脂蛋白E小鼠动脉粥样硬化的抗氧化机制与3-硝基酪氨酸的关系

目的探讨普伐他汀预防载脂蛋白E-/-小鼠动脉粥样硬化的抗氧化机制与3-硝基酪氨酸(3-nitrotyrosine,3-NT)的关系。方法将8周龄小鼠36只分为3组,空白对照组、模型组、普伐他汀组,每组12只。通过病理检测主动脉根动脉粥样硬化病变,Western blot法检测主动脉内3-NT和诱导型一氧化氮合酶的表达。结果普伐他汀组动脉粥样硬化病变的相对面积、3-NT和诱导型一氧化氮合酶的表达量显著低于模型组;模型组病变的相对面积、3-NT和诱导型一氧化氮合酶的表达量显著高于空白对照组。结论普伐他汀预防动脉粥样硬化的抗氧化机制之一可能是通过减少诱导型一氧化氮合酶致3-NT减少来实现的。     

霍山石斛对高脂诱导的LDLR基因敲除小鼠动脉粥样硬化和血管钙化的影响

目的 研究霍山石斛(DH)对高脂食物诱导的雄性低密度脂蛋白受体基因敲除(LDLR－/－)小鼠动脉粥样硬化(As)和血管钙化的影响,并初步探讨其作用机制。方法 LDLR－/－小鼠随机分为对照组和霍山石斛组(DH组)。喂养18周后对小鼠处以安乐死,收集血清、主动脉、肝脏等。分析血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)和低密度脂蛋白胆固醇(LDLC)的水平;对全主动脉及其根部切片进行油红O染色,检测动脉粥样硬化斑块面积;主动脉根部切片分别做天狼猩红和茜素红S染色,分析斑块稳定性和血管钙化程度;再对肝脏及其冰冻切片进行检测,分析其脂质积累情况。结果 霍山石斛喂食LDLR－/－小鼠18周后,与对照组比较,DH组小鼠血清TG水平下降(P＜0.05),但不影响血清中转氨酶及其他脂质水平。与对照组比较,DH组小鼠全主动脉及主动脉根部的粥样硬化斑块面积均减少约20%(P＜0.05);斑块损伤区域的胶原纤维含量增加约70%(P＜0.05),从而提高斑块的稳定性,且斑块中坏死核心的发生发展也受到明显抑制;对主动脉根部切片的茜素红S染色发现,对照组主动脉根部钙化面积占比1.34%,而DH组主动脉根部钙化面积占比为0.88%,减少了约34%(P＜0.01)。结论 霍山石斛可以抑制动脉粥样硬化和血管钙化的发生发展。     

肝X受体激动剂对高脂载脂蛋白E基因缺陷小鼠动脉壁一氧化氮合酶、增殖细胞核抗原和纤溶酶原激活物抑制剂1表达的影响

目的研究肝X受体激动剂3β-羟基-5α,6α-环氧胆烷酸甲酯和T-0901317对高脂载脂蛋白E基因缺陷小鼠动脉壁一氧化氮合酶、增殖细胞核抗原、纤溶酶原激活物抑制剂1表达的影响。方法以高脂饲养载脂蛋白E基因缺陷小鼠为动脉粥样硬化模型,分为无药对照组、3β-羟基-5α,6α-环氧胆烷酸甲酯干预组[10 mg/(kg.d)]和T-0901317干预组[10 mg/(kg.d)],每组6只小鼠,灌胃6周。用免疫组织化学SP法检测主动脉壁中诱导型一氧化氮合酶、内皮型一氧化氮合酶、增殖细胞核抗原、纤溶酶原激活物抑制剂1蛋白的表达。结果药物干预的两组主动脉壁中诱导型一氧化氮合酶的表达均显著低于对照组(P<0.01),而血管内皮细胞中内皮型一氧化氮合酶的表达均显著高于对照组(P<0.01)。各组增殖细胞核抗原和纤溶酶原激活物抑制剂1的表达无显著性差异(P>0.05)。结论肝X受体激动剂3β-羟基-5α,6α-环氧胆烷酸甲酯和T-0901317均可促进血管内皮细胞中内皮型一氧化氮合酶的表达,抑制动脉壁中诱导型一氧化氮合酶的表达。提示肝X受体激动剂还可通过调脂以外的其它途径,如抑制炎症反应和保护内皮功能等方面,发挥其抗动脉粥样硬化作用。     

载脂蛋白CⅢ通过增加氧化应激及内质网应激水平促进动脉粥样硬化病变

目的构建载脂蛋白CⅢ(Apo CⅢ)转基因小鼠,并与动脉粥样硬化易感的低密度脂蛋白受体(LDLR)敲除小鼠杂交,获得Apo CⅢ转基因+LDLR缺陷(Apo CⅢ+LDLR~(―/―))小鼠模型,开展Apo CⅢ对动脉粥样硬化影响及潜在机制的研究。方法 Apo CⅢ+LDLR~(―/―)小鼠与LDLR~(―/―)小鼠喂饲高脂饲料3个月,检测其血浆甘油三酯、总胆固醇、脂质过氧化产物和还原性谷胱甘肽水平。对小鼠的全主动脉和主动脉窦进行油红O染色及二氢乙啶染色,并提取主动脉的RNA和蛋白,分析相关基因的表达。结果 Apo CⅢ+LDLR~(―/―)小鼠喂饲高脂饲料后血浆甘油三酯水平明显高于LDLR~(―/―)小鼠,但总胆固醇水平差别不明显。主动脉全长和主动脉窦的染色显示动脉粥样硬化斑块明显增加。Apo CⅢ+LDLR~(―/―)小鼠血浆脂质过氧化产物8-异前列腺素和丙二醛水平明显升高,抗氧化物质还原性谷胱甘肽水平明显降低。对其主动脉进行二氢乙啶染色发现,动脉内活性氧水平明显增加。主动脉内氧化应激和内质网应激相关基因的mRNA和蛋白表达明显升高。提示Apo CⅢ可能通过增加动脉内的氧化应激和内质网应激,从而促进动脉粥样硬化斑块形成。结论 Apo CⅢ具有促动脉粥样硬化的作用,其机制可能与整体氧化应激水平的升高以及动脉壁氧化应激、内质网应激水平的增加有关。     

血红素氧合酶1—一氧化碳和一氧化氮合酶1—一氧化氮系统在动脉粥样硬化中的作用及其相关性研究

目的探讨血红素氧合酶1-一氧化碳和诱生型一氧化氮合酶-一氧化氮在动脉粥样硬化中的变化、相互关系及对动脉粥样硬化进程的影响. 方法家兔予以高胆固醇饮食(n=8)以及在高胆固醇饮食的同时经饮水给予L-精氨酸(n=8)或L-亚硝基精氨酸甲酯(n=8),或经腹腔注射血红素-L-赖氨酸盐(n=8)或锌原卟啉-9(n=8),共10周.结果与对照组比较,胆固醇组主动脉一氧化氮生成量显著减少,一氧化碳生成量则明显增加,一氧化氮合酶活性显著降低(P均<0.01),而血红素氧合酶1表达升高,主动脉斑块面积达40.2%±8.9%.与胆固醇组比较,外源性血红素-L-赖氨酸盐干预组的主动脉内膜斑块面积(26.6%±9.2%)明显缩小,主动脉一氧化碳的生成量和血红素氧合酶1的表达明显升高(P<0.01),但一氧化氮合酶活性和一氧化氮生成量较正常对照组显著降低(P<0.01),与胆固醇组比较则无显著性差异(P>0.05);与胆固醇组比较,外源性L-精氨酸组主动脉一氧化氮合酶活性显著升高, 一氧化氮生成量增加,主动脉斑块面积(28.1%±7.7%)明显缩小(P均<0.01),而血红素氧合酶1的表达和一氧化碳的生成较正常对照组明显升高,与胆固醇组比较则无显著性差异(P>0.05).与胆固醇组比较,血红素-L-赖氨酸盐干预组、L-精氨酸组的主动脉组织内c-myc及c-fos的mRNA和蛋白表达均显著降低(P均<0.01),而锌原卟啉组和L-亚硝基精氨酸甲酯组则无明显差异.结论动脉粥样硬化进程中,血红素氧合酶/一氧化碳和一氧化氮合酶/一氧化氮系统显示出互补及代偿性调节作用,血红素氧合酶系统通过对一氧化氮和一氧化氮合酶的调节和代偿机制抑制动脉粥样硬化病变的发展.     

葛根总黄酮对载脂蛋白E基因缺陷小鼠动脉粥样硬化斑块形成的影响

目的探讨葛根总黄酮对载脂蛋白E基因缺陷小鼠主动脉窦动脉粥样硬化斑块形成的影响。方法将载脂蛋白E基因缺陷小鼠随机分为模型组、葛根总黄酮低剂量组、葛根总黄酮高剂量组及阿托伐他汀阳性药物组。常规生物化学法测定血清总胆固醇、甘油三酯及高密度脂蛋白胆固醇水平;采用主动脉根部连续石蜡切片、苏木素伊红染色观察组织形态学改变,测定载脂蛋白E基因缺陷小鼠主动脉窦动脉粥样硬化斑块大小、动脉粥样硬化斑块与管腔面积比。结果4组小鼠共检出斑块65个,4组虽都有典型的粥样斑块或/及纤维斑块等中晚期动脉粥样硬化病变形成,但组织学观察发现模型组部分斑块体积较大,汇合成片,管壁弥漫性增厚,管腔较狭窄,而葛根总黄酮治疗组及阿托伐他汀阳性药物组动脉粥样硬化斑块病变较局限,管腔狭窄程度较轻,并且葛根总黄酮高、低剂量组及阿托伐他汀阳性药物组斑块面积与管腔面积之比值显著低于模型组(分别为0.11%±0.04%、0.27%±0.04%和0.76%±0.33%,P<0.01),葛根总黄酮高剂量组斑块面积与管腔面积比值显著低于葛根总黄酮低剂量组(P<0.01)。结论葛根总黄酮一定程度抑制载脂蛋白E基因缺陷小鼠动脉粥样硬化斑块进展,该作用可能与降低小鼠血脂作用无明显关系。     

姜黄素通过影响巨噬细胞的极性延缓动脉粥样硬化进展

目的研究姜黄素对ApoE基因敲除(ApoE~(-/-))小鼠动脉粥样硬化进展及斑块中巨噬细胞极性的影响。方法用高脂高胆固醇饮食饲养ApoE~(-/-)小鼠建立动脉粥样硬化模型,设立姜黄素治疗组、阿托伐他汀治疗组和高脂组;通过免疫组织化学(HE染色、油红O染色、Masson染色、苏木精染色)及免疫荧光染色检测主动脉斑块形态及不同亚型巨噬细胞的含量。通过实时荧光定量PCR检测主动脉组织中炎症因子的表达。结果姜黄素干预能减轻ApoE~(-/-)小鼠主动脉粥样硬化病变,并降低动脉粥样硬化斑块的易损指数。姜黄素降低动脉粥样硬化斑块内M1/M2巨噬细胞的比值,减少M1型巨噬细胞分泌的促炎因子白细胞介素1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子α(TNF-α)的表达,促进M2型细胞因子IL-10、Ym1和Fizz1的表达。结论姜黄素可通过影响斑块中巨噬细胞的极性、抑制相关的炎症反应,从而延缓ApoE~(-/-)小鼠动脉粥样硬化的进展。     

瑞舒伐他汀对ApoE-/-小鼠动脉粥样斑块中凋亡相关蛋白的影响

目的观察瑞舒伐他汀对Apo E-/-小鼠动脉粥样硬化斑块凋亡相关蛋白Bcl-2和Caspase-3表达的影响。方法 10只C57小鼠作为对照组,给予普通饮食,同品系22只Apo E-/-小鼠随机分为模型组(n=11)、干预组(n=11),高脂喂养8 w后,干预组给予瑞舒伐他汀悬液灌胃,模型组给予等量生理盐水。继续喂养12 w后所有老鼠处死,全自动生化仪检测血清血脂,光学显微镜观察各组小鼠主动脉斑块形态及面积,免疫组化法检测动脉粥样斑块Bcl-2和Caspase-3蛋白的表达。结果与对照组相比较,模型组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)明显升高(P0.05),高密度脂蛋白胆固醇(HDL-C)明显降低(P0.05);主动脉可见明显粥样斑块;Bcl-2表达明显减少,Caspase-3表达明显增多(P0.05)。与模型组比较,TC、TG、LDL-C明显降低(P0.05);干预组小鼠动脉粥样斑块面积减小(P0.05),Bcl-2表达明显增多,Caspase-3表达明显减少(P0.05)。结论高脂饮食可引起Apo E-/-小鼠主动脉凋亡相关蛋白Bcl-2和Caspase-3的变化,瑞舒伐他汀可以通过上调Bcl-2、下调Caspase-3的表达,抑制Apo E-/-小鼠动脉粥样硬化斑块的进展。     

一氧化氮及其合酶在家兔粥样硬化动脉的改变及L-精氨酸的作用

为探讨一氧化氮及其合酶在高胆固醇饮食诱导的动脉粥样硬化的改变及Ｌ－精氨酸的抗动脉粥样硬化作用,在高胆固醇饮食诱导的动脉粥样硬化模型上,检测了血清总胆固醇,血浆精氨酸,非对称性二甲基精氨酸和氧化型低密度脂蛋白浓度,主动脉一氧化氮合酶活性,一氧化氮生成量及内膜斑块面积。     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

Aims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.

Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P?<?0.05 (compare 2, version 1.02).

Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P?=?0.0027, RR?=?18.27 (20.0061–915.28)).

Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.     

PD-1/PD-L1抑制途径与自身免疫性糖尿病

PD-1(CD279)是一种负性协同刺激分子,属于CD28超家族成员,呈诱导性表达于活化的T、B和自然杀伤细胞表面.PD-L1(B7-H1,CD274)和PD-L2(B7-DC,CD273)是PD-1的两个配体.PD-1和PD-L1相互作用可以使活化的自身反应性T细胞获得负性信号,抑制其对自身抗原持续的免疫应答.若PD...     

Pandemic H1N1 influenza

The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.     

Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin

Abstract:  Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[ a ]pyrene or 7,12-dimethylbenz[ a ]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen-bioactivating enzyme. Melatonin (3–300 μ m ) decreased 7-ethoxyresorufin O -dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7-hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparent K _i values (mean ± S.E.M.) of 59 ± 1 (CYP1A1), 12 ± 1 (CYP1A2), 14 ± 2 (CYP1B1) and 46 ± 8 μ m (hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[ a ]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF-10A human mammary epithelial cells with melatonin (up to 300 μ m ) did not affect basal or benzo[ a ]pyrene-inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor-dependent pGudluc6.1-transfected MCF-10A cells treated with or without benzo[ a ]pyrene, as assessed in an in vitro cell-based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1-mediated chemical carcinogenesis.     

甲型H1N1流感合并肺炎的临床特点分析

目的通过对甲型H1N1流感合并肺炎的临床特点的分析。方法分析2009年月10月-2010年3月在我院入住的29例甲型H1N1流感合并肺炎患者的临床表现、实验室检查及胸部CT等资料。结果本组病例男性16例,女性13例。3例妊娠,13例合并有基础疾病。所有病例均有流感样前驱症状,呼吸道主要症状为发热、干咳少痰,严重者气短、呼吸困难、咯血。合并细菌感染时咯脓痰。肺部听诊无啰音或少啰音,合并哮喘时有哮鸣音,合并细菌感染时可有湿啰音。实验室检查65%白细胞不高或降低,41%心肌酶升高,58.6%存在低氧血症,35%呼吸衰竭。影像学表现多种多样：65.5%主要为单侧或双侧棉团样、团片样边界模糊高密度渗出影伴肺实变,其内见充气支气管征,病变沿支气管血管束分布。轻症及早期较局限,重症者及晚期病变融合呈双肺多发弥漫性改变。少数呈大叶及小叶性肺炎表现。预后大多良好,病死率6.9%。主要死亡原因为呼吸衰竭及大咯血。结论甲型H1N1流感合并肺炎是以甲型H1N1流感病毒肺炎为主要疾病的多种肺炎构成。甲型H1N1流感病毒肺炎临床表现具有流感病毒肺炎共性特点,其影像学表现有一定特征性。     

甲型H1N1与季节性H1N1流感病毒血凝素基因比较分析

目的分析泰安市2008～2009年度季节性流感与2009年度甲型H1N1流感病原学检测结果 ,比较季节性H1N1与甲型H1N1血凝素基因变异情况。方法选择国家级流感监测哨点医院以及暴发疫情的疫点,采集流感样病例的鼻咽拭子标本,通过RealtimePCR进行病毒检测,用MDCK细胞进行病毒分离,通过RT-PCR扩增血凝素HA1片段的基因并测序,利用生物信息学进行序列分析。结果 2008～2009年共检测鼻咽拭子标本283份,分离出流感病毒33株,分离阳性率为11.67%,其中季节性H1N1亚型31株。2009年5月1日～12月31日,检测鼻咽拭子标本996份,流感核酸检测阳性417份,阳性率为41.86%,其中甲型H1N1337份,季节性H1N1亚型1份。6株季节性H1N1病毒均在多个氨基酸位点上发生变异,与疫苗株A/Brisbane/59/2007(H1N1)比较,有11个位点发生了突变,其中5个位点位于抗原决定簇上;测序成功的6株甲型H1N1病毒在多个氨基酸位点发生变异,与疫苗株A/California/07/2009(H1N1)比较,有6个位点发生突变,其中1个位点位于抗原决定簇的B区。结论 2008～2009年度季节性H1N1为优势株,甲流暴发后,甲型H1N1成为绝对优势毒株。季节性H1N1分离株有多处氨基酸替换,抗原决定簇B区变异频繁;甲型H1N1病毒分离株的基因有变异,但关键位点第222位仍为D(天冬氨酸),与疫苗株相比抗原决定簇的关键位点变化不大。