CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制

目的探讨CYP1B1对高脂膳食诱导的成年小鼠脂肪代谢的作用。方法 CYP1B1基因敲除(KO)和野生型(WT)雄性成年C57/BL小鼠(6 w龄)各16只,给予低脂(LFD,30%)、高脂肪(HFD,60%)饲料共6 w。小鼠处死后取血清、附睾脂肪和肝脏组织检测相应的生化和分子生物学指标。结果 6 w高脂膳食后,KO小鼠能量摄入总量稍高于WT小鼠,但其体重增量和附睾脂肪组织重量均显著低于WT小鼠;WT小鼠脂肪细胞直径明显大于KO小鼠,且血糖、血清及肝脏组织中甘油三酯(TG)水平亦明显高于KO小鼠;肝脏组织RT-PCR结果显示,CYP1B1基因敲除后,启动脂肪形成的核因子及脂肪合成相关基因如CD36、SREBP1c、SCD1等表达下降,而调控脂肪氧化分解的基因如CPT-1α,UCP-2表达显著上升;蛋白印迹结果显示,CYP1B1基因敲除增强腺苷-磷酸激酶(AMPK)的磷酸化。结论 CYP1B1基因敲除对成年小鼠营养性肥胖的保护作用可能与AMPK磷酸化增强并调控肝脏中脂肪代谢相关基因的表达有关。     

CYP1B1在成年肥胖小鼠巨噬细胞浸润及组织炎症中的作用

目的探讨CYP1B1(cytochrome P450,family 1,subfamily B,polypeptide 1)缺失对成年小鼠巨噬细胞募集及组织炎症作用。方法选择6 w周龄SPF级CYP1B1基因敲除(KO)和野生型(WT)雄性小鼠,给予低脂肪(LFD)、高脂肪(HFD)饲料,喂养6 w后分别测定各组全血葡萄糖及血清胰岛素水平。利用葡萄糖耐量实验,判断糖耐量损伤情况。HE染色及免疫荧光检测小鼠附睾脂肪组织的巨噬细胞浸润情况。多重实时定量PCR(qRT-PCR)检测附睾脂肪组织及肝脏中巨噬细胞特异性蛋白(Emr1)及肿瘤坏死因子α(TNF-a)的表达水平。结果 CYP1B1敲除可以改善高脂膳食导致的胰岛素敏感性下降;在附睾脂肪组织中,CYP1B1基因缺失与高脂肪膳食均促进巨噬细胞的募集,但CYP1B1缺失抑制高脂膳食对炎症因子的诱导;在肝脏组织中,高脂膳食诱导巨噬细胞的浸润,但CYP1B1基因缺失抑制小鼠巨噬细胞浸润并下调组织炎症因子的表达。结论 CYP1B1基因缺失对高脂膳食诱导的肥胖及相关的胰岛素敏感性下降的保护作用可能是由其对炎症抑制的组织特异性决定的。     

脂肪组织炎症在CYP1B1基因敲除抑制小鼠营养性肥胖及其胰岛素抵抗中的作用

目的 探讨脂肪组织炎症在CYP1B1基因缺失小鼠保护营养性肥胖及其胰岛素抵抗中的作用和可能机制.方法 选择3周龄SPF级CYP1B1基因敲除(KO)和野生型(WT)雄性小鼠各16只,给予低(LFD)、高脂肪(HFD)饲料,每组8只,连续喂养11周.采用实时定量RT-PCR测定脂肪组织中巨噬细胞相关炎症因子、胰岛素通路中...     

Plin1基因敲除对肥胖小鼠脂肪组织炎症反应的影响及机制研究

目的 探究Plin1基因敲除对肥胖小鼠脂肪组织炎症水平的作用及其可能分子机制。方法 将雄性野生型C57BL/6J小鼠和Plin1基因敲除小鼠随机分为普通饲料组和高脂饲料组4组（n=6）,喂养12 w后,隔夜禁食自由饮水12h,眼眶采取所有新鲜血液及组织样本,并颈椎脱臼处死,取各组小鼠血清及部分附睾脂肪组织,酶法测定小鼠血清中游离脂肪酸（nonesterified fatty acid,NEFAs）的水平;酶联免疫吸附法（enzyme-linked immunosorbent assay,ELISA）试验测定小鼠血清和脂肪组织中肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白细胞介素6(Interleukin-6,IL-6)及单核细胞趋化因子1(monocyte chemotactic protein-1,MCP-1)的水平;免疫组织化学染色法观测F4/80的表达程度;免疫荧光染色法和Western blot法观察核因子κB (Nuclear Factor kappa-B,NF-κB)亚基P65的转位及表达水平和NF-κB亚基P65表达及磷酸化差异...     

Plin1基因敲除对肥胖小鼠脂质代谢的影响及机制

目的 研究Plin1基因敲除对高脂饮食诱导肥胖小鼠脂质代谢的影响并探究其可能的作用机制。方法 普通C57BL/6J小鼠12只，随机分为普通组和高脂组，每组6只，Plin1基因敲除小鼠12只，随机分为敲除普通组和敲除高脂组，每组6只。喂养12 w后称量各组小鼠体重，取出白色和棕色脂肪组织称重并用HE染色观察不同脂肪组织的形态变化；试剂盒检测小鼠血清脂质相关指标；WB法检测脂质代谢相关蛋白的表达。结果 与普通组相比，高脂组小鼠体重和脂肪组织重量显著增加（P <0.05）,TG、TC、LDL-C、Glycerin和FFA水平均显著升高（P <0.05），平均脂肪细胞面积变大（P <0.05），脂肪组织中SREBP1蛋白表达明显增加（P <0.05）,p-HSL和ATGL的蛋白表达量显著下降（P <0.05）；与高脂组相比，敲除普通组和敲除高脂组小鼠体重显著减轻，其脂肪重量和系数也明显下降（P <0.05），血清中TG、TC水平降低，HDL-C水平升高（P <0.05）,WAT细胞体积缩小，BAT细胞空泡增多，脂肪组织中SREBP1蛋白表达下降（P &...     

钙对饮食诱导肥胖大鼠抵抗素基因表达的影响

目的　探讨膳食钙对饮食诱导肥胖大鼠白色脂肪组织中抵抗素 (resistin)基因表达的影响。方法　以雄性Wistar大鼠为实验对象 ,用高脂饮食诱导大鼠肥胖模型。将肥胖大鼠按体重随机分为 4组 :A组为基础饲料组 ,B组为高脂低钙组 (含 0 2 5 %钙 ) ,C组为高脂正常钙组 (含 0 5 %钙 ) ,D组为高脂高钙组 (含 1%钙 )。于第 10周末处死动物 ,腹主动脉取血测定血糖、血清胰岛素、瘦素和肿瘤坏死因子α的水平 ,应用RT -PCR法测定白色脂肪组织中re sistinmRNA的水平。结果　D组体重和体脂含量显著低于C组 (P <0 0 5 ) ,与A组相近 ;各组血糖差异无统计学意义 (P >0 0 5 ) ,D组胰岛素水平显著低于C组 (P <0 0 5 ) ,而胰岛素敏感指数显著高于C组 (P <0 0 5 ) ,与A组相近 ;A组、B组和D组的瘦素水平均显著低于C组 (P <0 0 5 ) ,校正了体重影响后 ,只有A组显著低于C组 (P <0 0 5 ) ;D组肿瘤坏死因子α水平显著低于C组 (P <0 0 5 ) ,与A组相近 ;C组与A组相比 ,白色脂肪组织中resistinmRNA表达增强 ,D组resistinmRNA表达比C组明显降低 ,B组resistinmRNA表达比C组增强。结论　高钙膳食不仅可以降低饮食诱导肥胖大鼠的体重 ,而且可以通过促进瘦素分泌 ,降低肿瘤坏死因子α水平和抑制白色脂肪组织中resistin基因的表达     

高脂饮食对脂肪组织Sirtl基因表达影响

目的 观察高脂肪高能量对脂肪组织酵母染色质沉默因子1基因表达的影响.方法 利用高脂饮食制造肥胖倾向和肥胖抵抗动物模型,采用RT-PCR方法比较皮下和内脏白色脂肪组织SirtlmRNA表达水平.结果 高脂饮食干预导致动物体重生长分化,肥胖倾向组＞对照组＞肥胖抵抗组,差异有统计学意义(P＜0.05);3组动物每日进食量和能量摄入差异有统计学意义(P＜0.05);肥胖倾向组大鼠体脂肪含量大于肥胖抵抗组和对照组动物,差异有统计学意义(P＜0.05);高脂肪高能量负荷对大鼠脂肪组织Sirtl的表达有抑制作用.结论 Sinl基因可以作为调控体脂肪含量的靶基因.     

高脂膳食对SR-AⅠ/Ⅱ基因缺失小鼠脂代谢的影响

目的探讨A类Ⅰ型和Ⅱ型清道夫受体(scavenger receptor class A typesⅠandⅡ,SR-AⅠ/Ⅱ)基因缺失对高脂膳食小鼠脂质代谢的影响及其可能的作用机制。方法以SR-AⅠ/Ⅱ基因敲除与野生型雄性小鼠为对象,分别喂饲普通膳食和高脂膳食12w,应用酶法或油红O染色法检测脂质代谢(包括血脂水平和肝脏脂质水平)的变化,采用RT-PCR法检测肝脏B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和CD36的表达。结果SR-AⅠ/Ⅱ基因敲除鼠与野生型鼠相比,高脂膳食喂饲的第3、6、12w,其血清TG、TC、LDL、HDL均比野生型小鼠下降,肝细胞中脂滴的数量较多,体积较大,SR-BⅠmRNA表达上调,CD36mRNA的表达无差异。结论高脂膳食诱导SR-AⅠ/Ⅱ基因缺失小鼠脂质代谢的变化可能与肝脏SR-BⅠ表达升高及外周脂质向肝脏的逆向转运有关。     

CYP1B1基因敲除对高脂膳食诱导小鼠肥胖的抑制作用

目的 从整体水平探讨基因CYP1B1在机体脂肪代谢中的作用.方法 选择3周龄SPF级CYP1B1基因敲除(KO)和野生型(WT)雄性小鼠各16只,给予低(LFD)、高脂肪(HFD)饲料,每组8只.连续喂养11周.测定血清中甘油三酯(TG)的含量和肝脏组织中过氧化物酶体增殖物激活受体(PPAR-γ)、脂肪酸转移酶(CD3...     

n-3多不饱和脂肪酸对肥胖小鼠食欲调节因子表达的影响

【目的】 探讨n-3多不饱和脂肪酸(n-3 PUFAs)对饲料诱导肥胖小鼠食欲调节因子表达的影响。 【方法】 使用3~4周龄C57BL/6J雄性小鼠,随机分为3组,每组15只,分别给予两种高脂饲料(脂肪含量为34.9%,供能比为60%)-n-6PUFAs(来源于葵花籽油)饲料和n-3PUFAs(来源于鱼油)饲料喂养3个月;以正常脂饲料(脂肪含量为4.3%,供能比为10%)作为诱导肥胖鼠的对照。小鼠禁食12 h后,麻醉状态下心脏取血、脑和性腺周围脂肪。血浆瘦素含量测定采用酶联免疫分析法;脂肪组织瘦素及下丘脑瘦素受体、神经肽Y(NPY) 和促阿片-黑素细胞皮质素原(POMC)mRNA表达采用实时荧光定量PCR进行。 【结果】 两组高脂饲料诱导的肥胖小鼠体重和血浆瘦素浓度均高于正常脂饲料组小鼠,但n-3PUFAs高脂饲料组肥胖小鼠在两项指标的增高程度显著低于n-6PUFAs高脂饲料组肥胖小鼠。与正常脂饲料喂养小鼠相比,n-6PUFAs高脂饲料诱导肥胖小鼠脂肪组织瘦素和下丘脑瘦素受体、POMC mRNA表达水平显著升高,而NPY mRNA水平降低;n-3PUFAs高脂饲料诱导肥胖小鼠的上述4种基因mRNA表达则未发生变化。 【结论】 n-3PUFAs可减轻肥胖状态下瘦素及其受体、NPY、POMC等食欲调节因子表达的异常,在肥胖发生中起着积极作用。     

H1N1 vaccination

Early results (January to April) from the 2010 Canadian Community Health Survey show that an estimated 41% of Canadians (excluding those in the territories) aged 12 or older had been vaccinated for H1N1 by April 2010. The percentages were higher in the Atlantic provinces, Quebec and Saskatchewan than in Canada overall. Relatively high percentages of females and people aged 45 or older were vaccinated; the percentage of immigrants who had done so was relatively low. Being in a priority group (health-care worker, having children younger than 5 in the household, or having a chronic condition that could increase the risk for complications from H1N1) increased the likelihood of vaccination. A history of seasonal flu vaccination and having a regular doctor were also associated with H1N1 vaccination. Nearly three-quarters of those who had not been vaccinated reported that they did not think it was necessary.     

被动吸烟与cyp1b1、gstp1、sult1a1基因多态性对乳腺癌发病的影响

目的 探讨被动吸烟、cyp1b1、gstp1、sult1a1基因多态性及其联合作用对乳腺癌发病的影响。方法 2014 - 2015年间,采用病例-对照研究方法,收集病例794例,对照805例。问卷调查收集研究对象信息。采用飞行质谱技术,进行cyp1b1、gstp1、sult1a1基因单核苷酸多态性分型检测。采用多因素非条件 logistic 回归,分析环境烟草烟雾暴露及cyp1b1、gstp1、sult1a1基因多态性与乳腺癌发病风险的关系。结果 调整年龄、教育程度、家庭年总收入、职业、婚姻状况后,环境烟草烟雾暴露与gstp1基因多态性未发现协同作用。以环境烟草烟雾低暴露且携带 cyp1b1 rs1056836 C等位基因为参照,环境烟草烟雾高暴露且携带 GG 基因在绝经前女性中乳腺癌风险明显增高（OR = 1.678,95%CI:1.039～2.711）。以环境烟草烟雾组合低暴露且携带sult1a1 rs9282861GG基因型为参照,环境烟草烟雾高暴露且携带A等位基因绝经前乳腺癌风险明显增高（OR = 2.389,95%CI:1.157～4.931）,但交互作用系数无统计学意义。结论 环境烟草烟雾高暴露与cyp1b1 及sult1a1基因对乳腺癌发病风险可能存在协同作用,但尚扩大样本进行验证。     

Echo-AM1-1 encephaloscope]

A new miniature model of the A-mode ultrasonic echoencephaloscope, 0.88 MHz, has been developed and adopted to practical use in neurology. The device contains a detector for amplitude determination of echopulsation and curve (echopulsograms) recording. It is highly sensitive, cost-effective, which enhances the quality of rapid diagnosis of central nervous diseases, including those of vascular genesis, in in- and outpatient settings.     

接种甲型H1N1流感疫苗后患甲型H1N1流感分析

目的 分析接种甲型H1N1流感疫苗后发生甲型H1N1流感感染的病例,探讨发病原因,为进一步提高疫苗预防效果提供参考依据.方法 对接种甲型H1N1流感疫苗后发生甲型H1N1流感感染148例,进行回顾性调查分析.结果 接种甲型H1N1流感疫苗11176例.发生甲型H1N1感染148例,感染率1.32%,其中1～14 d感染81例,感染率0.72%,＞15 d感染67例,感染率0.60%.结论 甲型H1N1流感病毒裂解疫苗是一种安全高效的疫苗,不足之处尚待进一步探讨、完善.     

NF1 gene and neurofibromatosis 1

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of patients with NF1 is probably reduced by 10-15 years, and malignancy is the most common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies. A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recurring mutation has been identified. Most studies have not found an obvious relation between particular NF1 mutations and the resulting clinical manifestations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. No general, population-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinical features of NF1 would not outweigh the costs of screening.     

GSTM1及GSTT1和GSTP1基因多态性对尿中1-羟基芘水平的影响

目的 研究GSTM1、GSTT1和GSTP1基因多态性对多环芳烃接触工人尿中1-羟基芘(1-OHP)水平的影响.方法 分别选取2个炼焦厂共447名多环芳烃职业接触工人(接触组)和某线材厂220名非职业接触工人(对照组)作为研究对象,采用高效液相色谱法测定尿中1-OHP水平,采用线性回归统计模型分析GSTM1和GSTT1缺失型及GSTP1 I105V位点的多态性对不同人群尿中1-OHP水平的修饰作用.结果 接触组工人尿中1-OHP浓度为4.61 μmol/mol Cr,明显高于对照组(0.34μmol/mol Cr),差异有统计学意义(P＜0.05).接触类别和吸烟分别是影响尿中1-OHP水平的主要因素,在控制各混杂因素的影响后,线性回归分析显示,接触组尿中1-OHP水平和GSTP1 I105V位点多态性有关(单基因分析,P=0.012;多基因分析,P=0.011),对总体样本,单基因模型和多基因模型均显示,尿中1-OHP水平可能和GSTT1缺失型多态有关(P=0.055),多基因交互作用分析显示,GSTT1和GSTP1基因多态对接触组尿中1-OHP水平具有交互作用.结论 谷胱甘肽硫转移酶(GSTs)基因的多态性对接触多环芳烃工人尿中1-OHP水平有影响.

Abstract：

Objective To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels. Methods Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions. Results The urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 μmol/mol Cr, P＜0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P=0.012; multi-gene model, P=0.011 ) and with GSTT1 null type in the analysis including all subjects (P=0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP. Conclusion Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.     

Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China

The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.