目的:应用甲基CpG结合蛋白-2(methyl-CpG-binding protein 2,MECP2)基因突变筛查方法,检测孤独症患者的MECP2基因,探讨孤独症与MECP2基因的关系。方法:收集男性孤独症44例,均满足孤独症《美国精神障碍诊断和统计手册》第4版诊断标准,应...目的:应用甲基CpG结合蛋白-2(methyl-CpG-binding protein 2,MECP2)基因突变筛查方法,检测孤独症患者的MECP2基因,探讨孤独症与MECP2基因的关系。方法:收集男性孤独症44例,均满足孤独症《美国精神障碍诊断和统计手册》第4版诊断标准,应用变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)筛查MECP2基因变异,并进行DNA测序鉴定。对存在MECP2基因错义突变的病例进行家系调查。结果:在44例患者中经DHPLC筛查阳性和DNA测序发现,4例患者存在不同的MECP2基因突变,包括c.590C>T(T197M)和c.602C>T(A201V)2种错义突变,以及c.1053C>G、c.897C>T 2种同义突变;17例的内含子3位于Exon 4前74位点C>T,为SNP(rs2071569);1例c.602C>T错义突变患者家系调查发现,突变来源于母亲及外祖父,母亲呈杂合子,为X染色体随机失活,母亲与外祖父智力均正常,外祖父有抑郁症。结论:在男性孤独症患者中,存在MECP2基因较高的变异率,MECP2基因在孤独症致病中可能起着一定作用,不除外是孤独症的易感基因。展开更多
Objective： To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthyiisothiocyanate （ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decocti...Objective： To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthyiisothiocyanate （ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decoction （茵陈蒿汤, YCHD） using an ultra pressure liquid chromatography （UPLC） method. Methods： Rats were divided into a normal group and a model group, after modeled by 4% ANIT （75 mg/kg） for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g/kg, and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）] and bilirubins [total bilirubin （TBIL）, direct bilirubin （DBIL）], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS2.1.1 software. Results： The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration （tmax were both 0.25 h, the maximum concentration （Cmax） were 4.533 iμ g/mL and 6.885 μg/mL, and their area under concentration-time curve （AUC）o→24h were 16.272 and 32.981, respectively. There was a 51.88% and 100.46% increase in Cmax and AUCo-t （P〈0.05）, but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution （P〈0.05）, respectively. Conclusions： Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats, but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.展开更多
文摘目的:应用甲基CpG结合蛋白-2(methyl-CpG-binding protein 2,MECP2)基因突变筛查方法,检测孤独症患者的MECP2基因,探讨孤独症与MECP2基因的关系。方法:收集男性孤独症44例,均满足孤独症《美国精神障碍诊断和统计手册》第4版诊断标准,应用变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)筛查MECP2基因变异,并进行DNA测序鉴定。对存在MECP2基因错义突变的病例进行家系调查。结果:在44例患者中经DHPLC筛查阳性和DNA测序发现,4例患者存在不同的MECP2基因突变,包括c.590C>T(T197M)和c.602C>T(A201V)2种错义突变,以及c.1053C>G、c.897C>T 2种同义突变;17例的内含子3位于Exon 4前74位点C>T,为SNP(rs2071569);1例c.602C>T错义突变患者家系调查发现,突变来源于母亲及外祖父,母亲呈杂合子,为X染色体随机失活,母亲与外祖父智力均正常,外祖父有抑郁症。结论:在男性孤独症患者中,存在MECP2基因较高的变异率,MECP2基因在孤独症致病中可能起着一定作用,不除外是孤独症的易感基因。
基金Supported by the National Natural Science Foundation of China (No.81073069)
文摘Objective： To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthyiisothiocyanate （ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decoction （茵陈蒿汤, YCHD） using an ultra pressure liquid chromatography （UPLC） method. Methods： Rats were divided into a normal group and a model group, after modeled by 4% ANIT （75 mg/kg） for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g/kg, and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）] and bilirubins [total bilirubin （TBIL）, direct bilirubin （DBIL）], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS2.1.1 software. Results： The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration （tmax were both 0.25 h, the maximum concentration （Cmax） were 4.533 iμ g/mL and 6.885 μg/mL, and their area under concentration-time curve （AUC）o→24h were 16.272 and 32.981, respectively. There was a 51.88% and 100.46% increase in Cmax and AUCo-t （P〈0.05）, but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution （P〈0.05）, respectively. Conclusions： Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats, but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.
