β_3肾上腺能受体基因Trp64Arg变异与胰岛素抵抗的关系

目的 :观察中国人群β3 肾上腺能受体 (β3 AR)基因 Trp 64Arg的变异频率 ,以及此基因变异与肥胖、胰岛素抵抗及非胰岛素依赖性糖尿病 ( NIDDM)的关系。方法 :选取互相之间无任何亲缘关系的汉族NIDDM病人 1 32例 ,年龄 ( 55.41± 1 2 .3)岁。选取无亲缘关系的汉族非 NIDDM80人 ,年龄 ( 54.1 2± 1 3.6)岁。对上述对象查体 ,查血生化指标及空腹血清 C-肽 ( C- P)。用 PCR- RFLP方法检测β3 AR基因 Trp 64Arg变异。结果 :Arg 64纯合子发生 NIDDM的相对危险性是 1 .54。Arg 64纯合子的 NIDDM病人发病年龄较早( 37.33± 6.98岁 vs.45.69± 1 1 .0 1岁 ,P<0 .0 5)。Arg64纯合子与 Trp64纯合子相比 ,前者体重指数较大( 2 8.56± 2 .58vs.2 4 .72± 5.1 2 ,P<0 .0 5) ,血 TG水平较高 ( 2 .56± 1 .2 1 mmol/L vs.1 .71± 1 .31 mmol/L,P<0 .0 5) ,血 HDL- C水平较低 ( 1 .0 1± 0 .2 3mmol/L vs.1 .32± 0 .44mmol/L,P<0 .0 5) ,空腹血 C- P水平较高 ( 1 .0 5± 0 .34pmol/L vs.0 .77± 0 .2 3pmol/L,P<0 .0 5) ,动脉舒张压较高 ( 1 1 .30± 1 .75k Pa vs.1 0 .1 0± 1 .63k Pa,P<0 .0 5)。Trp64Arg杂合子也有以上倾向 ,但与 Trp64纯合子相比无显著性差异。结论 :β3 AR基因的 Trp64Arg变异与肥胖、胰岛素抵抗?

Constructing Biophore of Uroselective α1-Adrenoceptor antagonist

Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.