具有减肥活性的B3-肾上腺素受体激动剂代谢产物的研究

Expression ofβ3-adrenoceptor mRNA in the lipocytes of normal weight and obese humans was examined by reverse transcription polymerase chain reaction(RT-PCR) with β-actin as an internal standard. The relative β3-adrenoceptor mRNA expression ratios (（β3-AR mRNA Volume/β-actin Volume）of the normal weight volunteers control group and obese group were 1.56 ± 0.17 (n=183) and 1.98 ± 0.18 (n=165), respectively and there was a significant difference ( p < 0.05), suggesting that a lower expression ofβ3-adrenoceptor mRNA may be related to the pathogeny of obesity. To investigate whether the polymophism of β3-adrenoceptor gene are associated with obesty in Chinese Han population with obesty , 186 obese patients with essential hypertension and insulin resistant were selected as test group , and 177 normal weight healthy persons were selected as control. On the studies with PCR-RFLP, the frequency of Trp64Arg mutation of β3-adrenoceptor gene was higher in the test group than that in the control group (7.8 % vs 1.3 % , p < 0.05) . Thusβ3-adrenoceptor gene mutation seems to be one of the hereditary factors in some obeses patients. Thirty metabolites from 12 β3- adrenoceptor agonists with known molecular structure, such as CL316，243 and CGP12177,were separated from the rats serum and prepared with RP-HPLC.Twenty seven of the thirty metabolites could not stimulate lipid mobilization through lipolysis and through inhibition of insulin stimulated glucose transport in human fat cells, however another 3 metabolites showed rather weak stimulating action on lipid mobilization through lipolysis at 10-5 mol/L vitro. The molecular structures of these 3 metabolites will be reformed, then their productions by reformation will be tested further..

多个B3受体激动剂对大鼠有显著减肥作用，但对肥胖病人却无效。它们在大鼠体内的代谢产物是否对人有减肥功效？至今未见报道。拟用制备型HPLC分离上述代谢产物，用富含B3受体的肥胖病人脂肪细胞为材料，以放射配体-受体结合抑制试验，促脂肪分解和抑2-脱氧葡萄亲说戎副辏秆《匀酥鞠赴舾械纳鲜龃徊铮晃兄萍醴市乱┐蚧