目的观察祛风及开窍类引经药柴胡、防风及冰片对六味地黄丸有效成分在眼不同组织分布和代谢的影响,探讨引经药是否可以增加药物有效成分在眼部的靶向性聚集。方法将252只家兔随机分为6组,每组42只,对照组正常饲养不作处理,其它组分别用蒸馏水、六味地黄丸、六味地黄丸+防风、六味地黄丸+柴胡、六味地黄丸+冰片溶液灌胃,在灌胃后0.25、O.50、0.75、1.00、2.00、4.00、8.00h各时间点每组随机取6只家兔,采用液质联用技术检测房水、玻璃体、视网膜中莫诺苷和马钱苷的含量,比较各组含量差异。结果房水中检测发现莫诺苷、马钱苷的浓度曲线变化趋势较一致,均在灌胃后0.25~1h达到峰值,在8h后基本清除完全,其中六味地黄丸+冰片组的马钱苷、莫诺苷的浓度在0.25~0.75h均较六味地黄丸组、六味地黄丸+防风组、六味地黄丸+柴胡组高,差异有统计学意义(P〈0.05)。各组有效成分在玻璃体中的浓度均很低.马钱苷的曲线呈波动趋势,各个时间点各组两两比较差异均无统计学意义(P〉0.05),莫诺苷的曲线在0.25。1h达到峰值,随后在8h基本清除完全,其中六味地黄丸+冰片组的莫诺苷浓度在0.25~0.75h均较六味地黄丸组、六味地黄丸+防风组、六味地黄丸+柴胡组高,差异有统计学意义(P〈0.05);其它各组两两比较,差异均无统计学意义(P〉0.05)。各组视网膜内莫诺苷和马钱苷的浓度也偏低,其中六味地黄丸+冰片组马钱苷和莫诺苷的浓度在0.25h较六味地黄丸组、六味地黄丸+防风组、六味地黄丸+柴胡组高,差异有统计学意义(P〈0.05);其他组两两比较,差异均无统计学意义(P〉0.05)。结论冰片可以增加六味地黄丸有效成分在房水、玻璃体和视网膜的浓度,这可能是引经药的作用机制之一。
OBJECTIVE To observe the effect of wind-expelling and orifice-opening meridian-lead-in drug on the intraocular distribution of active ingredients from Liuwei Dihuang pills, and to investigate whether meridi- an-lead-in drugs could increase the targeting accumulation of active ingredients in the eye. METHODSA total of 240 rabbits wererandomly divided into 6 groupsevenly.Subjects in control group were fed routinely without any treat- ment, the other groups were administrated with distilled water, Liuwei Dihuang pills, Liuwei Dihuang pills plus Bing- pian, Liuwei Dihuang pills plus Fangfeng, Liuwei Dihuang pills plus Chaihu respectively by gavage. At time point as 0.25h, 0.Sh, 0.75h, l.0h, 2.0h,4.0h,8.0h after gavage, 6 rabbits randomly chosen from each group were tested for their content of Morroniside and Loganinin aqueous humor, vitreous and retina by LC-MS, and the difference between groups was compared as well. RESULTS In the aqueous humor, the content of Morroniside and Loganin shared sim-ilar trend, both reached peak at 0.25 to lh after gavage, and were both dispelled totally 8hours after garage. A- mong them, the contents of Morroniside and Loganin in Liuwei Dihuang pills plus Bingpian at the time points be- tween 0.25h-0.75 h were significantly higher than that of Liuwei Dihuang pills group, Liuwei Dihnang pills plusFangfeng group, Liuwei Dihuang pills plus Chaihu group (P〈0.05). The contents of all groups were in low level in vitreous. Loganin content varied and showed no significant difference among all the groups (P〉0.05). Morroniside reached peak between 0.25 and lh after gavage, and then was dispelled totally at 8th post gavage. The contents of Morroniside in Liuwei Dihuang pills plus Bingpian group at the time points between 0.25h and 0.75h were signifi- cantly higher than that of Liuwei Dihuang pills group, Liuwei Dihuang pills plus Fangfeng group, Liuwei Dihuang pills plus Chaihu group(P〈0.05 ). There was no significant difference between other two groups in pair(P〉0.05 ). Th