Regulation of neurosteroid biosynthesis is primarily mediated by the steroidogenic acute regulatory(StAR,commonly known as STARD1)protein.The StAR protein,by mobilizing the transport of intra-mitochondrial cholesterol...Regulation of neurosteroid biosynthesis is primarily mediated by the steroidogenic acute regulatory(StAR,commonly known as STARD1)protein.The StAR protein,by mobilizing the transport of intra-mitochondrial cholesterol,mediates the rate-limiting step in neurosteroid biosynthesis.The first steroid produced by the action of cytochrome P450 cholesterol side-chain cleavage enzyme(CYP11A1),at the mitochondrial inner membrane,is pregnenolone(the precursor of all neurosteroids),which is then converted to various steroids by tissue-specific enzymes.展开更多
文摘目的在携带CYP2C19功能缺失等位基因的轻型卒中或短暂性脑缺血发作(transient ischemic attack,TIA)患者中,探讨胰岛素抵抗对替格瑞洛-阿司匹林与氯吡格雷-阿司匹林在降低卒中复发风险的疗效和安全性方面的影响。方法基于氯吡格雷用于急性非致残性脑血管事件高危人群的疗效研究-Ⅱ(Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular EventsⅡ,CHANCE-2)试验,纳入基线三酰甘油、空腹血糖、身高、体质量、腰围数据资料完整的患者。以三酰甘油葡萄糖-体质量指数(triglyceride-glucose-body mass index,TyG-BMI)、三酰甘油葡萄糖-腰围(TyG-waist circumference,TyG-WC)、三酰甘油葡萄糖-腰高比(TyG-waist-to-height ratio,TyG-WHtR)作为胰岛素抵抗替代指标,按各指数的中位数将患者划分为高、低胰岛素抵抗亚组。主要疗效指标和安全性指标分别为90 d内卒中复发和中重度出血。结果在高TyG-WC和高TyG-WHtR组中,替格瑞洛-阿司匹林较氯吡格雷-阿司匹林显著降低卒中复发风险(P<0.05),风险比(hazard ratio,HR)分别为0.70(95%CI:0.53-0.92)和0.74(95%CI:0.56~0.97);在高TyG-BMI、低TyG-WC、低TyG-WHtR和低TyG-BMI亚组中,替格瑞洛-阿司匹林虽显示疗效优势,但差异无统计学意义(P>0.05)。各亚组中两治疗组间中重度出血风险差异无统计学意义(P>0.05)。结论以高TyG-WC或高TyG-WHtR为特征的高胰岛素抵抗患者,可能是基于CYP2C19基因型选择替格瑞洛-阿司匹林治疗的敏感人群。
基金supported in part by funding from the Department of Internal Medicine and The CH Foundation(to PRM).
文摘Regulation of neurosteroid biosynthesis is primarily mediated by the steroidogenic acute regulatory(StAR,commonly known as STARD1)protein.The StAR protein,by mobilizing the transport of intra-mitochondrial cholesterol,mediates the rate-limiting step in neurosteroid biosynthesis.The first steroid produced by the action of cytochrome P450 cholesterol side-chain cleavage enzyme(CYP11A1),at the mitochondrial inner membrane,is pregnenolone(the precursor of all neurosteroids),which is then converted to various steroids by tissue-specific enzymes.
