五味子制剂对大鼠他克莫司血药浓度的影响及对肝损伤的防护作用

目的: 探讨临床常用的两种五味子制剂五酯胶囊和双环醇对大鼠免疫抑制剂他克莫司血药浓度的影响及对肝损伤的防护作用。方法: 将55只大鼠随机分成4组,空白对照组10只, FK506单独给药组,FK506+五酯胶囊联合给药组,FK506+双环醇联合给药组,每组各15只。分别以FK506 1 mg/kg,五酯胶囊 11.25 mg/kg,双环醇 200 mg/kg,每日1次连续灌药 21 d,给药后第7、14、21天禁食 8 h 后采血检测FK506浓度和肝功能,处死大鼠取肝脏行病理学检查。结果: 未加五味子制剂的FK506单药组血药浓度上升缓慢,加用五酯胶囊组和双环醇组均具有提高FK506血药浓度的作用。五酯胶囊组他克莫司血药浓度上升比较快,与对照组相比给药 7 d 差异即出现统计学意义(F=11.043,P=0.002),14 d(F=98.167,P=0.000)和 21 d(F=57.457,P=0.000),差异更加显著。但双环醇组与五酯胶囊组相比各时间点差异均无统计学意义。双环醇保肝作用明显,与对照组相比,给药 7 d 后ALT显著降低,差异具有统计学意义(F=12.83,P=0.001),给药 14 d(F=11.58,P=0.002)和 21 d(F=22.27,P=0.000)差异更加显著。五酯胶囊组降低ALT的作用弱起效慢,7、14、21 d 与对照组相比均无统计学意义。双环醇组能使白蛋白(ALB)保持在较高水平,各时间点与对照组相比差异具有统计学意义(P＜0.05)。FK506对肝细胞的损伤发生在用药早期,在组织学表现为肝细胞水肿、变性和炎症细胞浸润。结论: 五酯胶囊和大剂量双环醇均具有提高大鼠他克莫司血药浓度的作用,并且起效较快;FK506对肝细胞损伤发生在用药早期,双环醇具有预防FK506所致肝损伤的作用。

Effects of two types of schisandra preparations on the plasma concentrations of immunosuppressant tacrolimus in rats and protective effect of liver injury

AIM: To investigate the effects of two types of schisandra preparations,WZ capsules and bicyclol,on the plasma concentrations of immunosuppressant tacrolimus in rats with liver injury.METHODS: 55 rats were randomly divided into four groups: control group(n=10), the other three groups(n=15, in each case) only FK506 treatment group (1 mg/kg), FK506+WZ co-treatment group group(capsules 11.25 mg/kg), FK506+bicyclol combination group(bicyclol 200 mg/kg).once every day for 21 successive days,after 8 h fasting at 7,14,21 d the administration,the concentrations of FK506 and the liver function were detected. After the experiment the rats were killed,the changes of livers of rats in each group were observed.RESULTS: Plasma concentrations of FK506 in FK506 treatment group were increased slowly without schisandra preparations, the plasma concentrations of FK506 were increased in FK506+WZ co-treatment group and FK506+bicyclol combination group.The plasma concentrations of FK506 in FK506+WZ co-treatment group were increased fastly,compared with the control group, there was statistically significant difference in FK506+WZ co-treatment group,7 d after administration (F=11.043, P=0.002), 14 d (F=98.167, P=0.000) and 21 d (F=57.457, P=0.000). Compared with the FK506+WZ co-treatment group,there was no statistically significant difference in FK506+bicyclol combination group at each time point. Compared with the control group,bicyclol had liver protection obviously,the level of ALT was decreased 7 d after administration(F=12.83,P=0.001),14 d(F=11.58,P=0.002),21 d(F=22.27,P=0.000),there was statistically significant difference.The effect of on reducing ALT was weak and work slowly in FK506+WZ co-treatment group, which had no statistical significance,compared with the control group in 7 d,14 d,21 d after administration. Compared with control group,bicyclol group could keep ALB at a higher level,there was statistically significant difference at each time point(P＜0.05). The damage of FK506 to hepatocyte occurred early after administration, histologically characterized by edema, degeneration of liver cells and inflammatory cell infiltration.CONCLUSION: The WZ capsules and high-dose of bicyclol can rapidly increase the plasma concentrations of FK506,the damage of FK506 to hepatocyte occurs early after administration. Bicyclol can prevent liver from the damage of FK506.