血脑屏障上 P-糖蛋白的功能：年龄和性别效应。
P-glycoprotein function at the blood-brain barrier: effects of age and gender.
机构信息
Department of Nuclear Medicine & PET Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
出版信息
Mol Imaging Biol. 2012 Dec;14(6):771-6. doi: 10.1007/s11307-012-0556-0.
PURPOSE
P-glycoprotein (Pgp) is an efflux transporter involved in transport of several compounds across the blood-brain barrier (BBB). Loss of Pgp function with increasing age may be involved in the development of age-related disorders, but this may differ between males and females. Pgp function can be quantified in vivo using (R)-[(11)C]verapamil and positron emission tomography. The purpose of this study was to assess global and regional effects of both age and gender on BBB Pgp function.
PROCEDURES
Thirty-five healthy men and women in three different age groups were included. Sixty minutes dynamic (R)-[(11)C]verapamil scans with metabolite-corrected arterial plasma input curves were acquired. Grey matter time-activity curves were fitted to a validated constrained two-tissue compartment plasma input model, providing the volume of distribution (V (T)) of (R)-[(11)C]verapamil as outcome measure.
RESULTS
Increased V (T) of (R)-[(11)C]verapamil with aging was found in several large brain regions in men. Young and elderly women showed comparable V (T) values. Young women had higher V (T) compared with young men.
CONCLUSIONS
Decreased BBB Pgp is found with aging; however, effects of age on BBB Pgp function differ between men and women.
目的
P-糖蛋白（Pgp）是一种外排转运体，参与多种化合物穿过血脑屏障（BBB）的转运。随着年龄的增长，Pgp 功能的丧失可能与年龄相关疾病的发展有关，但这种情况在男性和女性之间可能有所不同。可以使用（R）-[[11]]C]维拉帕米和正电子发射断层扫描来在体内定量测定 Pgp 功能。本研究的目的是评估年龄和性别对 BBB Pgp 功能的全局和区域影响。
程序
纳入了 35 名处于三个不同年龄组的健康男性和女性。采集了 60 分钟动态（R）-[[11]]C]维拉帕米扫描，并伴有校正代谢物的动脉血浆输入曲线。灰质时间活动曲线拟合到经过验证的约束两组织室血浆输入模型，提供（R）-[[11]]C]维拉帕米的分布容积（V（T））作为结果测量。
结果
在男性的几个大脑区域中，随着年龄的增长，（R）-[[11]]C]维拉帕米的 V（T）增加。年轻和老年女性的 V（T）值相当。年轻女性的 V（T）高于年轻男性。
结论
随着年龄的增长，BBB Pgp 减少；然而，年龄对 BBB Pgp 功能的影响在男性和女性之间存在差异。
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