布地奈德对支气管哮喘小鼠树突细胞胸腺基质淋巴生成素受体表达的影响

目的 探讨布地奈德对支气管哮喘(简称哮喘)小鼠胸腺基质淋巴生成素(TSLP)-树突细胞(DC)途径和Th2极化的影响及其机制.方法 将18只清洁级雌性6～8周龄BALB/c小鼠按随机数字表法分为哮喘组[卵清白蛋白(OVA)腹腔致敏,OVA吸入激发]、布地奈德(BUD)干预组(OVA腹腔致敏,气道内吸入OVA和布地奈德)和对照组(以生理盐水代替OVA混悬液腹腔注射及雾化吸入),每组6只.观察各组小鼠生物学及肺组织病理学改变,收集BALF,并分离培养小鼠脾脏树突细胞,酶联免疫吸附试验( ELISA)检测BALF中TSLP水平、树突细胞上清液中TSLP受体(TSLPR)水平和DC-T细胞共培养上清液中细胞因子.流式细胞仪检测树突细胞表型.多组间比较采用单因素方差分析,组间两两比较采用t检验.结果 布地奈德干预组支气管及血管周围炎症细胞浸润轻于哮喘组.哮喘组BALF中TSLP水平[(44.0±5.1)ng/L]和树突细胞培养上清液中TSLPR水平[(19.7±2.2) ng/L]均高于对照组[分别为(14.2±3.6) ng/L和(10.4±1.2) ng/L,t值分别为11.74和9.13,均P＜0.01],BALF中TSLP水平与IL-5水平和嗜酸粒细胞呈正相关(r值分别为0.89和0.82,均P＜0.05);布地奈德干预组BALF中TSLP水平[(19.2±5.8) ng/L]及树突细胞表达TSLPR水平[(12.5 ±2.8) ng/L]均低于哮喘组[分别为(44.0±5.1)ng/L和(19.7±2.2)ng/L],差异有统计学意义(t值分别为-7.86和-4.97,均P＜0.01);布地奈德干预组BALF及DC-T细胞共培养上清液中IL-5[分别为(41±4)ng/L和(28 ±9) ng/L]低于哮喘组[分别为(81 ±8) ng/L和(51±14) ng/L],差异有统计学意义(t值分别为-11.00和-3.35,均P＜0.01),3组间IFN-γ差异无统计学意义(F值分别为0.97和0.82,均P＞0.05);布地奈德干预组与哮喘组相比CD40、CD80和CD86等树突细胞表型下降.结论 布地奈德影响树突细胞表型,下调BALF中TSLP水平和树突细胞表达TSLPR水平,可能通过影响TSLP-DC途径而抑制哮喘Th2极化反应.     

高脂饮食性非酒精性脂肪性肝病小鼠肝脏陷窝蛋白-1的变化

目的 探索陷窝蛋白-1在高脂饮食性非酒精性脂肪性肝病(NAFLD)发病中的作用.方法 给予12只10周龄雄性C57BL/6小鼠高脂高胆固醇饮食14周,建立NAFLD的动物模型作为实验组.同时,普通饮食饲养同种系小鼠6只作为对照组.第14周末处死全部小鼠,比较两组体质量、肝质量和血脂变化.分别用实时荧光定量PCR(qPCR)和Western印迹法检测陷窝蛋白-1在NAFLD小鼠肝组织中的基因和蛋白表达水平变化.苏木精-伊红染色后光学显微镜下观察小鼠肝脏的脂肪变性情况,免疫组织化学染色后观察陷窝蛋白-1在肝组织中分布的变化.采用t检验比较两组肝组织中陷窝蛋白-1 mRNA及蛋白水平的差异,Mann-whitney U检验分析不同程度脂肪肝小鼠的肝脏陷窝蛋白-1表达的免疫组织化学积分差异.结果 实验组小鼠在高脂高胆固醇饮食14周后全部发生NAFLD,其中重度9只,中度3只.与对照组比较,实验组小鼠的血清TC[(1.940±0.300) mmol/L比(3.771±0.800) mmol/L,t=-3.760]、高密度脂蛋白胆固醇[(1.120±0.066)mmol/L比(2.224±0.420) mmol/L,t=-5.474]、低密度脂蛋白胆固醇[(0.510±0.191) mmol/L比(1.241±0.660) mmol/L,t=-3.332]均显著升高(P均＜0.01),但TG差异无统计学意义(P＞0.05).实验组小鼠肝脏陷窝蛋白[1的mRNA(1.536±0.226比0.980±0.272,t=3.371,P＜0.05)和蛋白水平(0.643±0.240比0.100±0.130,t=-4.847,P＜0.01)均显著高于对照组.免疫组织化学结果显示,表达增加的陷窝蛋白-1主要分布于肝细胞膜、脂滴膜和细胞质中.结论 高脂高胆固醇饮食诱导的NAFLD小鼠肝脏陷窝蛋白1水平上调,可能参与了NAFLD的发病机制.     

单性日本血吸虫感染对高脂饮食诱导小鼠2型糖尿病的预防作用研究

目的观察单性日本血吸虫感染对改善小鼠2型糖尿病症状的作用,并探讨其机制。方法 C57BL/6小鼠随机分为正常饮食组、高脂饮食组、高脂+雌性组和高脂+雄性组,高脂+雌性组和高脂+雄性组小鼠分别感染雌性和雄性血吸虫,并以高脂饲料喂养;每周称量小鼠体重,在各组小鼠体重出现显著变化时,做葡萄糖耐量试验;先后给予2次低浓度链脲佐菌素(STZ)(70 mg/kg)腹腔注射,检测各组小鼠血糖变化,并检测小鼠血脂;流式细胞仪检测小鼠脾细胞IL-4和IFN-γ分泌水平,分析小鼠Th1/Th2免疫应答类型。结果高脂饲料喂养12周后,高脂+雄性组体重显著低于高脂饮食组和高脂+雌性组,体重趋向正常饮食小鼠;注射葡萄糖溶液后30 min,高脂+雄性组血糖为(16.97±3.09)mmol/L,与正常饮食组(21.6±1.96)mmol/L和高脂+雌性组(20.84±2.93)mmol/L比较差异有统计学意义(P0.05或p0.01),与高脂饮食组(20.24±3.89)mmol/L比较差异无统计学意义(P0.05);经两次STZ诱导后,正常饮食组在第24周血糖达到峰值(13.76±0.93)mmol/L,高脂饮食组在第25周达到峰值(10.24±1.48)mmol/L;高脂+雌性组血糖峰值在第26周,为(9.84±0.99)mmol/L,高脂+雄性组血糖峰值在第25周,为(7.7±2.62)mmol/L。4组小鼠血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平差异均无统计学意义(均P0.05);高脂+雄性组脾细胞IL-4和IFN-γ分泌水平显著高于正常饮食组和高脂+雌性组(均P0.05)。结论雄性血吸虫感染可以抵抗高脂饲料诱导的小鼠体重增加和血糖上升,改善小鼠葡萄糖代谢,拮抗STZ诱导的血糖升高,并诱导Th1和Th2型免疫应答细胞因子分泌增加。     

N-乙酰半胱氨酸对非酒精性脂肪性肝炎模型小鼠肝细胞线粒体自噬的影响

目的在非酒精性脂肪性肝炎模型小鼠中探索N-乙酰半胱氨酸(NAC)对肝细胞线粒体自噬的影响。方法C57BL/J6小鼠分别给予16周的正常饮食、高脂高糖(HFCD)饮食和HFCD+NAC饮食。比较HE和Masson染色、ALT、AST、IL-1β、肝组织甘油三酯水平评价小鼠肝损伤。通过免疫荧光染色观察线粒体自噬。比较3组小鼠肝组织内线粒体自噬标志物在mRNA和蛋白水平的变化。结果HFCD组小鼠较对照组ALT[(24.9±2.12)比(176.7±44.32)U/L,P<0.05]、AST[(76.7±9.06)比(291.3±39.66)U/L,P<0.05]、IL-1β[(2.94±0.08)比(9.12±1.21),P<0.05]显著升高,HFCD+NAC组较HFCD组肝功能好转,IL-1β降低[(9.12±1.21)比(6.77±0.58)ng/L,P<0.05]。HFCD组小鼠肝组织内Parkin、PINK1表达降低,同时LC3B II/I比值降低,P62表达量增高。提示HFCD组小鼠肝细胞线粒体自噬水平降低。HFCD+NAC组较HFCD组线粒体自噬水平升高,差异有统计学意义(P<0.05)。结论NAC可能通过改善肝细胞线粒体自噬,进而减轻肝细胞炎症进展。     

戒烟对大鼠血清瘦素、脂联素等炎症因子的影响

目的 通过研究戒烟对大鼠血清瘦素、脂联素、白介素6(IL-6)及C反应蛋白(CRP)水平的影响,探讨瘦素和脂联素等炎症因子在吸烟所致慢性阻塞性肺疾病炎症反应中的作用.方法 雄性Wistar大鼠30只,随机分为吸烟组、戒烟组及对照组,每组各10只.吸烟组每次吸烟10支,每天吸烟2次,每周吸烟6 d,共吸烟20周;戒烟组为吸烟20周后戒烟10周.采用酶联免疫吸附法检测各组大鼠血清瘦素、脂联素及CRP水平,采用双抗体夹心酶联免疫吸附法检测各组大鼠血清IL-6水平.结果 ①与对照组[(128.00±13.25) ng/L]比较,吸烟组[(56.23±8.64)ng/L]及戒烟组[(60.36±7.42)ng/L]血清瘦素水平均降低(P值均<0.05);戒烟组与吸烟组比较差异无统计学意义.②与对照组L(0.369±0.032)μg/L]比较,吸烟组[0.322±0.045)μg/L]血清脂联素水平降低(P<0.05),而戒烟组L(0.333±0.059)μg/L]与对照组、吸烟组比较差异无统计学意义.③与对照组[(23.94±4.44)ng/L]比较,吸烟组[(39.67±3.13)ng/L]及戒烟组[(34.27±7.01)ng/L]血清IL-6水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).④与对照组[(494.49±124.44)μg/L]比较,吸烟组[(809.50±141.66)μg/L]及戒烟组[(632.60±182.85)μg/L]血清CRP水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).⑤脂联素水平分别与IL-6和CRP呈负相关(γ值分别为-0.198、-0.489,P值均<0.05);IL-6水平与CRP呈止相关(γ=0.598,P<0.05).结论吸烟可使大鼠血清瘦素与脂联素水平下降,IL-6与CRP水平升高;戒烟后,瘦素、脂联素水平呈上升趋势,IL-6和CRP水平则相应下降.此外,脂联素水平分别与IL-6和CRP呈负相关.提示瘦素、脂联素等炎症因子可能参与吸烟所致慢性阻塞性肺疾病的炎症反应.     

肥胖大鼠血脂和体脂肪变化及心室肌细胞内钙离子强度与心律失常发生的关系

目的 观察高脂饮食诱导肥胖(DIO)大鼠血脂和体脂肪变化,探讨心室肌细胞内钙离子强度与心律失常发生的关系.方法 健康雄性SD大鼠60只,体质量200～250 g.将大鼠按体质星随机分为对照组(15只)和高脂饮食组(45只),高脂饮食组采用高脂饮食诱导法建立肥胖大鼠模型.喂养12周后,在高脂饮食组筛选体质量增加明显的大鼠进入肥胖组(15只).两组各选8只大鼠舌下注射0.1 ms/kg BaCl2,诱导心律失常.应用标准Ⅱ导联心电图连续监测1 h,评价大鼠心律失常发生率及严重程度.采集两组大鼠腹主动脉血,分离血清,测血清总胆同醇,甘油三酯,低密度脂蛋白胆固醇和高密度脂蛋白胆固醇.分离大鼠肾周脂肪,睾周脂肪和肠系膜脂肪,称重,计算体脂比.酶解法分离大鼠单个心室肌细胞,应用激光共聚焦技术记录细胞内钙离子强度([Ca2+]i).结果 肥胖组大鼠体脂比[(7.71±0.74)%]明显高于对照组[(4.69±0.37)%],两组比较差异有统计学意义(t＝3.650,P＜0.05),血清总胆固醇,甘油三酯和低密度脂蛋白水平,肥胖组[(1.26±0.04),(0.58±0.10),(0.51±0.04)mmol/L]与对照组[(0.92±0.08),(0.29±0.03),(0.31±0.04)mmol/L]比较显著增高(t值分别为3.801,2.778,3.536,P＜0.05),肥胖组大鼠心律失常发生率高于对照组(X2＝5.333,P＜0.05),心律失常评分肥胖组(2.5±0.6)高于对照组(0),肥胖组大鼠心室肌细胞内钙离子强度(247.96±20.03)明显高于对照组(174.25±23.13),两组比较差异有统计学意义(t=2.409,P＜0.05).结论 肥胖大鼠心律失常发生率增加,血脂升高,心肌细胞内钙离子积聚是引发肥胖源性心律失常的主要机制之一.     

SIRT1对高糖高脂培养胰岛微血管内皮细胞炎性反应激活的影响

目的 分析高糖、高脂环境下胰岛微血管内皮细胞(IMVC)分泌E-选择素、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β的变化,研究沉默信息调节蛋白1(SIRT1)/核因子-κB信号途径异常在内皮细胞炎性反应激活中的作用.方法 合成含绿色荧光蛋白报告基因的小鼠SIRT1基因重组质粒,以Lipofectamine 2000转染IMVC.之后将IMVC分为4组:正常对照组、高糖高脂组、高糖高脂+ SIRT1基因转染组、高糖高脂+基因转染对照组.高糖高脂组以33.3 mmol/L葡萄糖+0.5mmol/L棕榈酸处理48 h.高糖高脂+SIRT1基因转染组在高糖高脂处理前以SIRT1基因重组质粒预处理48 h;高糖高脂+基因转染对照组在高糖高脂处理前以空质粒进行预处理48 h.应用实时荧光定量PCR法检测SIRT1基因转染效果及各组核因子-κB的mRNA水平,应用酶联免疫吸附法测定细胞培养上清中TNF-α、IL-1β、E-选择素的水平.结果 与正常对照组相比,高糖高脂组SIRT1 mRNA表达明显下降(0.58 ±0.12,P＜0.01);而高糖高脂+SIRT1基因转染组的SIRT1基因表达明显升高,与高糖高脂组相比差异显著[(1.55±0.43)比(0.65±0.37),P＜0.01].与正常对照组相比,高糖高脂组核因子-κB mRNA(1.59 ±0.32,P＜0.01)、E-选择素[(48.46±1.04)比(67.12±0.57) ng/L,P＜0.01]、TNF-α[(467.46±8.98)比(621.14±11.26) ng/L,P＜0.01]、IL-1β[(63.32±1.48)比(118.43±1.40) ng/L,P＜0.01]的水平明显升高(P＜0.01).与高糖高脂组相比,高糖高脂+SIRT1基因转染组核因子-κB mRNA (0.95±0.31,P＜0.01)及TNF-α[(451.38±15.91)比(618.89±7.23) ng/L,P＜0.01]明显下降(P＜0.01),E-选择素、IL-1β无明显变化(P＞0.05).结论 高糖高脂环境下,IMVC存在炎性反应激活,可释放大量炎性反应细胞因子.SIRT1-核因子-κB-TNF-α通路异常与IMVC的炎性反应激活密切相关,早期干预该信号通路可能在预防及治疗2型糖尿病的胰岛炎性反应中具有重要意义.     

角蛋白18片段与炎症相关因子在脂肪性肝病诊断中的作用

目的 探讨非酒精性脂肪性肝病(NAFLD)伴代谢综合征(MS)的患者细胞角蛋白18片段、炎症相关因子的表达水平,为临床早期预防NAFLD伴有MS的患者向严重肝病进展提供依据.方法 采用横断面调查研究,成组设计.入组85例脂肪肝患者及20例正常对照者.根据是否伴MS分为三组:NAFLD +MS组、NAFLD组、NC组.采用酶联免疫吸附法(ELISA)检测各组血清中细胞角蛋白18片段、炎症相关因子肿瘤坏死因子(TNF)α、白细胞介素6(IL-6)表达水平.通过速率散射比浊法检测血清超敏C-反应蛋白(hs -CRP)表达水平.结果 (1)血清细胞角蛋白18片段(M30)在NAFLD+MS组中高表达[(143±38.7)ng/L],与NAFLD组[(125±36.05)ng/L]、NC组[(118±30.40) ng/L]比较差异有统计学意义(P＜0.05).(2)炎症相关因子TNF α在NAFLD+ MS组[(316±74.5)ng/L]和NAFLD组[(308.6±87.5) ng/L]升高、与NC组[(241.7±75.8)ng/L]比较差异有统计学意义(P＜0.05),在NAFLD组与NAFLD+ MS组间无统计学差异(P =0.677).(3)hs-CRP和IL -6表达水平在MS+ NAFLD组高表达,分别为1.63(1.01,2.42 ) mg/L和(2.18 +0.87)pg/L,与NAFLD、NC组间均具有统计学差异.结论 细胞角蛋白18片段和炎症相关因子在NAFLD伴MS患者中明显增高,提示可能向严重肝病发展,临床工作中应注意对该类患者严密监测.     

整合素β1基因沉默对支气管哮喘小鼠气道平滑肌功能的影响

目的 探讨整合素β1基因沉默对支气管哮喘(简称哮喘)小鼠气道平滑肌细胞(ASMC)增殖和分泌功能的影响.方法 原代培养正常及哮喘模型小鼠ASMC,分别取各自第5代ASMC进行实验,利用RNA干扰(RNAi)技术沉默ASMC的整合素β1基因,RT-PCR技术观察沉默前后ASMC整合素β1 mRNA表达水平变化,蛋白印迹检测沉默前后ASMC整合素β1蛋白含量变化;四甲基偶氮唑盐(MTT)法检测整合素β1基因沉默前后ASMC细胞增殖变化;流式细胞仪测定整合素β1基因沉默前后ASMC细胞周期分布及细胞凋亡率变化情况;ELISA检测整合素β1 基因沉默前后ASMC分泌的白细胞介素(IL)-6及受激活调节正常T细胞表达和分泌因子(RANTES)的含量变化.结果 (1)哮喘PBS对照组RT-PCR显示整合素β1 mRNA(0.907±0.041)较正常PBS对照组(0.527±0.027)显著增高(t=24.632,P＜0.05),哮喘siRNA干预组(0.503±0.034)较哮喘PBS对照组明显减低(t=24.079,P＜0.05),正常siRNA干预组较正常PBS对照组无显著性变化(t=1.077,P＞0.05);(2)Western blot检测显示哮喘PBS对照组整合素β1蛋白表达(0.733±0.067)较正常PBS对照组(0.386±0.044)显著增高(t=13.622,P＜0.05),哮喘siRNA干预组(0.453±0.074)较哮喘PBS对照组显著减低(t=8.880,P＜0.05),正常siRNA干预组较正常PBS对照组无显著性变化(t=1.908,P＞0.05);(3)MTT实验显示3～5 d的吸光度(A)值哮喘PBS对照组较同期正常PBS对照组 显著增强(均P＜0.05),哮喘siRNA干预组的A值较同期哮喘PBS对照组显著降低(均P＜0.05),正常siRNA干预组与正常PBS对照组差异无统计学意义(均P＞0.05);(4)哮喘PBS对照组ASMC处于增殖状态的S期+G2/M期ASMC比例为[(49±4)%],明显高于正常PBS对照组[(34±4)%](t=8.035,P＜0.05),哮喘siRNA干预组ASMC的S期+G2/M期ASMC比例(42±7)%明显低于哮喘PBS对照组(t=2.212,P＜0.05),正常siRNA干预组与正常PBS对照组差异无统计学意义(t=0.699,P＞0.05);(5)哮喘PBS对照组的凋亡率[(3.9±1.4)%]较正常PBS对照组[(7.4±0.5)%]显著升高(t=7.465,P＜0.05),哮喘siRNA干预组凋亡率[(12.6±2.4)%]明显高于哮喘PBS对照组(t=9.839,P＜0.05),正常siRNA干预组凋亡率与正常PBS对照组相比差异无统计学意义(t=2.094,P＞0.05);(6)哮喘PBS对照组IL-6[(545±28)ng/L]、RANTES分泌值[(345±28)ng/L]高于正常PBS对照组[分别为(219±26)ng/L和(138±16)ng/L,均P＜0.05],哮喘siRNA干预组分泌量[分别为(348±26)ng/L和(250±24)ng/L]显著低于哮喘PBS对照组(t值分别为6.192和4.590,均P＜0.05),而正常siRNA干预组较正常PBS对照组差异无统计学意义(均P＞0.05).结论 靶向ASMC整合素β1基因沉默能抑制哮喘模型小鼠ASMC的增殖、降低分泌功能并促进ASMC凋亡.     

不同剂量阿托伐他汀对老年急性脑梗死患者血清脂联素和趋化素水平的影响

目的探讨不同剂量阿托伐他汀对老年急性脑梗死患者血清脂联素和趋化素水平的影响。方法连续性纳入120例急性脑梗死患者,随机分为低剂量组(阿托伐他汀20mg/d)、高剂量组(阿托伐他汀40mg/d)和对照组,每组40例。分别于治疗前和治疗2周后检测血清脂肪因子(脂联素和趋化素)和TNF-α及白细胞介素8(IL-8)水平变化。结果与治疗前比较,治疗2周后低剂量组和高剂量组患者血清趋化素、TNFα和IL-8明显下降,脂联素明显上升(P0.05),且高剂量组趋化素[(3.2±1.2)mg/L vs(5.2±2.2)mg/L,P0.05],TNF-α[(61.5±18.5)ng/L vs(70.6±20.1)ng/L,P0.05]和IL-8[(24.5±7.2)ng/L vs(28.2±8.1)ng/L,P0.05]明显低于低剂量组,脂联素明显高于低剂量组[(12.3±4.9)mg/L vs(9.1±3.8)mg/L,P0.05]。阿托伐他汀与TNF-α(r=0.610,P=0.001)、IL-8(r=0.351,P=0.005)和趋化素(r=0.624,P=0.001)的变化值呈正相关,与脂联素的变化值呈负相关(r=-0.402,P=0.003),其中高剂量阿托伐他汀较低剂量的相关性更高(P0.05,P0.01)。结论急性脑梗死患者及早应用阿托伐他汀干预治疗,可以明显调节趋化素和脂联素水平异常,降低炎症损伤程度。     

Noonan syndrome and related disorders: Alterations in growth and puberty

Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548–555, 1994). Recently, a mutation in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al., Nat Genet, 29:465–468, 2001) was found to be present in about 50% of individuals with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis Child, 17:652–662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri, Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413–427, 1986) and Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42–48, 2003). All three of these syndromes share similar cardiac defects and all have postnatal short stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi, Tanaka et al., Nat Genet, 37:1038–1040, 2005) have been found in the Costello syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu, Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki, Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294–296, 2006) in the Cardio-facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can now be explained since each is caused by germline mutations that are major components of the RAS-MAPK pathway. This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis.     

先天性心脏病的基因型和表型关系

目前先天性心脏病的病因学已经从胚胎学迅速深入到遗传学领域,尤其是确定其基因型和表型关系。近来,关于 Noonan综合征、马方综合征和长QT综合征的基因型和表型关系的研究已取得长足的进展,在先天性心脏病分子生物学研究上具有代表意义,对特定基因突变的临床应用和深入认识不仅有助于作出先天性心脏病更为敏感和特异的诊断而且有利于促进治疗方法的提高。     

Brugada syndrome in a 4-year-old child with Lemierre syndrome—A case report

Brugada syndrome is a rare arrhythmogenic disease with characteristic electrocardiogram (ECG) findings. Fever represents an important triggering factor. We report the case of a 4-year-old Saudi boy who was diagnosed with Lemierre syndrome and subsequently developed Brugada syndrome.     

肝肾综合征的研究进展

肝肾综合征（Hepatorenal syndrome,HRS）是肝功能障碍终末期的严重并发症,以肾脏血管显著收缩为特征,最终导致肾脏血流灌注和肾小球滤过率明显下降,肾脏的水钠排泄功能受损。尽管HRS是一种可逆性、功能性肾功能损伤,但一旦发生,预后极差,存活率很低。目前临床上血管活性药物、白蛋白的应用可以改善肾功能,提高患者生存率,但最终有效治疗方案仍是肝移植。随着对其发病机制、临床特点的进一步了解及药物的治疗进展,国际腹水协会对其定义及诊断标准达成了新的共识。     

心肾综合征的临床研究进展

心肾综合征一词已广泛用于进行性充血性心力衰竭引起的肾功能下降。为了概括心脏与肾脏之间复杂的因果关系,心肾综合征分为5种临床亚型:Ⅰ型:急性心肾综合征;Ⅱ型:慢性心肾综合征;Ⅲ型:急性肾心综合征;Ⅳ型:慢性肾心综合征;Ⅴ型:继发性心肾综合征。心肾综合征是慢性肾功能不全和慢性心力衰竭中治疗的难题,现就心肾综合征近年来临床研究进展进行综述。     

Inherited arrhythmic disorders in Japan

The clinical and genetic characteristics of inherited arrhythmic disorders in Japan are briefly summarized. The incidence of hereditary long QT syndrome (LQTS) in Japan seems comparable to that in western countries. The genotypes are mainly LQT1 and LQT2; LQT3 and other types are rare. Mutations found in Japanese LQTS families are mostly novel compared to mutations reported in other countries and in different ethnic populations. Functional assays of the mutants in heterologous expression systems have disclosed novel mechanisms of current suppression in LQT1 and LQT2, and of gain of function in LQT3. Mutations in KCNJ2 may provide a new genotype (LQT7) of LQTS. In addition, mutations or single nucleotide polymorphisms in the channel genes responsible for LQTS (KvLQT1, HERG, and SCN5A) may predispose to drug-induced LQTS. A relatively high prevalence of Brugada syndrome is suspected in the Japanese population, and 1 of approximately 2,000 asymptomatic individuals present Brugada-type ECG changes upon annual examination. Genetic screening of the symptomatic Brugada syndrome and suspected cases has revealed SCN5A mutations in only approximately 12%. Therefore, the genetic basis of the majority of cases is not known. The expressed Na+ current of SCN5A mutant channels showed the phenotype of decreased channel function commonly seen in Brugada mutations. A case of idiopathic ventricular fibrillation was found to have a novel mutation in SCN5A, in which the expressed current showed marked suppression of channel function.     

Mechanisms of drug-induced proarrhythmia in clinical practice

Drug-induced proarrhythmia represents a great challenge for those involved in the development of novel pharmaceuticals and in the regulatory bodies for drug approval as well as for the prescribing clinicians. Our understanding of the mechanisms that underlie drug-induced proarrhythmia has grown dramatically over the last two decades. A growing number of cardiac and non-cardiac agents have been shown to alter cardiac repolarization predisposing to fatal cardiac arrhythmias such as ventricular tachycardia or ventricular fibrillation and sudden cardiac death. These agents may induce the phenotype of long QT syndrome and less commonly of short QT syndrome and Brugada syndrome (BS). Although, genetic susceptibility underlie drug-induced proarrhythmia in certain cases, current data are limited regarding this topic. The present review surveys the current published literature on the mechanisms and the offending medical agents that predispose to drug-induced long QT syndrome, short QT syndrome and BS. Drug-induced proarrhythmia should be considered as a predictor of sudden cardiac death and should prompt critical re-evaluation of the risks and benefits of the suspicious medication. Survivors of drug-induced proarrhythmia and family members require careful examination and possibly genetic testing for the presence of a channelopathy. Treating physicians are advised to follow the lists of agents implicated in drug-induced proarrhythmia in order to minimize the risk of arrhythmia and sudden cardiac death.