抗肝炎药双环醇的研究(新)精要.pptVIP

抗肝炎药双环醇的研究 中国医学科学院药物研究所 李 燕 研究背景 现状 乙肝：HBsAg 1.2亿 乙肝患者 3000万 肝癌 30万/年 丙肝：3.2% Margolis et al. 1991（3.5亿) 抗病毒 抗肝损伤 抗纤维化 双环醇抗肝损伤作用及机制研究 双环醇对不同类型肝损伤的保护作用 Group Dosage mM GPT release U/106 cells GOT release U/106 cells MDA formation OD/106 cells Normal - 3.6±0.4 3.3 ±0.3 2.9 ±0.4 CCl4 - 10.2 ±2.2 7.0 ±0.5 6.8 ±2.4 Bicyclol 1.0 4.4 ±0.3** 3.8 ±0.2*** 1.6 ±0.5** 0.1 7.8 ±1.0 5.8 ±0.4*** 5.6 ±1.4** 0.001 8.4 ±0.8 6.0 ±0.2*** 5.8 ±0.9 肝细胞膜保护作用（形态学） 促进肝细胞蛋白合成 （同位素标记） Drug concentration 0 10-3M 10-4M Bicyclol 996±57 3053 ±29*** 1883 ±2*** Malotiate 893 ±59 1089 ±16* 1168 ±2** 降低升高的转氨酶（生化） 体外研究 双环醇对化学性肝损伤的保护作用 体内研究 血清氨基转移酶平均值（单位/dl) Effect of bicyclol on the elevation of serum aminotransferases and total bilirubin in LPS /GalN -intoxicated mice (n = 8). ##P0.01 vs control group, **P0.01 vs LPS /GalN group. Treatment Prothrombin time(s) Prothrombin activity (%) Normal 10.48±0.30 175±31 LPS /GalN 13.38±0.95## 67±13## Dexamethasone 10.58±0.45** 171±51** Bicyclol (300 mg/kg×3) 11.69±0.56** 105±21** Bicyclol (300 mg/kg×1) 12.23±0.62** 88±14** Effect of bicyclol on prothrombin time and prothrombin activity in LPS /GalN -intoxicated mice (n = 8) ##P0.01 vs normal group ; **P0.01 vs LPS/GalN group. Effect of bicyclol on the level of liver protein and glycogen in APAP-intoxicated mice (n =6). ##P0.01 vs control group; *P0.05, **P0.05 vs APAP group. (protein, g/L; glycogen, mg/g liver; FBG, mg/ml. ) 双环醇对化学性肝损伤的保护作用 Effect of bicyclol on the activity of liver ATPase in APAP-intoxicated mice(n=6). Liver specimens were collected at 16h after APAP injection. ##P0.01 vs control group. *p0.05 vs APAP group. A C D ?15,000 B D F ?30,000 A,B: 正常对照 C,D: 扑热息痛 对照 E,F: 百赛诺 150mg/kg Effect of bicyclol on mitochondria membrane potential In APAP- intoxicated mice (n=5). APAP group; Bicyclol 300×3, Bicyclol 300 mg/kg administration for 3 times 1h before APAP injection, Bicyclol 300×1, Bicyclol 300 mg/ kg administrati