御风胶囊对老年血淤大鼠血小板聚集功能及血浆中血栓素B2,6-酮前列腺素F1α含量的干预效应

背景:临床实验证明御风胶囊(黄芪、当归、川芎、远志、丹参等中药)组成有益气活血、祛淤生新的功效,其影响途径可能与血小板聚集功能和血浆中血栓素B,6-酮前列腺素F1α含量的变化有关。目的:观察御风胶囊对血小板聚集功能的影响及其作用机制。设计:随机对照动物实验。单位:哈尔滨医科大学大庆校区药理组。材料:实验于2000-05/2004-07在哈尔滨医科大学大庆校区药理实验室完成。选择Wistar雄性老年大鼠40只,平均鼠龄8～10周,平均体质量(550±150)g‘Wistar雄性青年大鼠8只,平均鼠龄4～6周,平均体质量(230±120)g。方法:Wistar青年雄性大鼠8只为青年对照组;40只老年大鼠为血淤模型,采用数字表法随机分为5组,每组8只,即阿司匹林组,御风胶囊(由黄芪、当归、川芎、远志、丹参组成,黑龙江中医药大学附属二院制剂室提供胶囊制剂)低剂量组、中剂量组、高剂量组和老年模型组。分别给予阿司匹林溶液5.5g/kg,御风胶囊0.33g/kg,0.66g/kg,1.32g/kg,老年模型组和青年对照组不给药。连续灌胃22d,2次/d,末次给药1h后,采用血小板聚集法和放免法测量血小板聚集功能和血浆中血栓素B2,6-酮列腺素F1α的含量。主要观察指标:血小板聚集功能;血栓素B2和6-酮列腺素F1α的含量及比值。结果:48只动物全部进入结果分析①老年模型组血小板聚集率均高于其他五组(P<0.01)。②御风胶囊高剂量组1min、5min和最大血小板聚集率均低于阿司匹林组,分别为(7.96±2.17),(6.38±1.66),(14.33±2.87)ng/L和(31.95±3.94),(35.29±6.54),(38.68±7.46)ng/L,(P<0.01);中剂量组5min血小板聚集低于阿司匹林组[(13.96±1.66),(35.29±6.54)ng/L,(P<0.01)]。③御风胶囊低剂量组、中剂量组、高剂量组、阿司匹林组、青年对照组血栓B2含量均低于老年模型组(P<0.01)。④御风胶囊高剂量组血栓B2低于低剂量组[(100.13±8.90),(127.00±20.99)ng/L,(P<0.01)]。⑤御风胶囊高剂量组、中剂量组、青年对照组血栓素B2/6-酮-前列腺素F1α均低于老年模型组[(0.62±0.17),(0.69±0.14),(1.75±0.17),(1.11±1.12)ng/L,(P<0.05)]。结论:御风胶囊高剂量、中剂量可降低血浆中血栓素B2含量和提高6-酮前列腺素F1α含量,改善两者比值,对保持血栓素B2/6-酮前列腺素F1α之间的平衡有显著作用。低剂量组亦有作用,但效果不如高、中剂量组,可认为有预防作用。

Interventional effect of Yufeng capsule on function of platelet aggregation and contents of thromboxane B2 and 6-ketoprostaglandin F1 alpha in blood plasma of gerontic rats with blood stasis

BACKGROUND: Clinical experiments indicates that Yufeng capsule (composed of milkvetch root, angelica, szechwan lovage rhizome, senega and salvia miltiorrhiza) is effective for benefiting vital energy, circulating blood flow,dispelling gores and killing inflammation. The mechanism may be associated with the function of platelet aggregation, changes of contents of thromboxane B (TXB) and 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 α) in plasma.OBJECTIVE: To observe the influence of Yufeng capsule on the platelet aggregation and its mechanism.DESIGN: Randomized controlled animal trial.SETTING: Department of Pathology, Daqing Branch of Harbin Medical University.MATERIALS: The experiment was performed at the Laboratory of Pharmacology, Daqing Branch of Harbin Medical University from May 2000 to July 2004. A total of 40 Wistar male gerontic rats with mean age of (8-10) weeks and mean body mass of (550±150) g and 8 Wistar male young rats with mean age of 4-6 weeks and mean body mass of (230±120) g were selected.METHODS: The 8 Wistar male youth rats were selected as youth control group. The 40 Wistar male gerontic rats were selected as the blood stasis model, and according to the numeration table method they were classified into 5 groups: aspirin group, low-dose Yufeng capsule group, the middle-dose Yufeng capsule group, high-dose Yufeng capsule group and gerontic model group, with 8 rats in each group. The Yufeng capsule was constituted by milkvetch root, angelica, szechwan lovage rhizome, senega and salvia miltiorrhiza, and provided by the Preparation Office, Second Affiliated Hospital,Heilongjiang University of Chinese Medicine. Respectively the rats were injected with aspirin solution (5.5 g/kg), Yufeng capsule (0.33 g/kg, 0.66 g/kg and 1.32 g/kg), successively for 22 days by gastric perfusion, twice a day.Those in the gerontic group and youth control group were not treated with any drug One hour after last time administration, function of platelet aggregation(PAG), contents of thromboxane B2 (TXB2) and 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 α) in plasma were examined with platelet aggregation method and radioimmunoassay.MAIN OUTCOME MEASURES: Function of platelet aggregation; contents of TXB2 and 6-keto-PGF1 α as well as ratio of TXB2 to 6-keto-PGF1α.RESULTS: Totally 48 animals were involved in the result analysis. ①The PAG was higher in the gerontic model group than other groups (P ＜ 0.01).②One minute platelet aggregation rate (PAG1), five minutes platelet aggregation rate (PAG5)and the maximal platelet aggregation rate (PAGM) in the high-dose Yufeng capsule group were lower than those in the aspirin group[(7.96±2.17), (6.38±1.66), (14.33±2.87) ng/L and (31.95±3.94),(35.29±6.54), (38.68±7.46) ng/L, respectively(P ＜ 0.01 )]. PAG5 in the middle-dose group was lower than that in the aspirin group [(13.96±1.66),(35.29±6.54) ng/L, (P ＜ 0.01 )]. ③TXB2 content in the low-dose Yufengcapsule group, middle-dose Yufeng capsule group, high-dose Yufeng capsule group, aspirin group and youth control group was lower than that in the gerontic model group (P ＜ 0.01). ④The TXB2 content in the high-dose Yufeng capsule group was lower than that in the low-dose Yufeng capsule group [( 100.13±8.90), (127.00±20.99) ng/L, (P ＜ 0.01 )]. ⑤TXB2/6-ke-to-PGF1 α in the high-dose Yufeng capsule group, middle-dose Yufeng capsule group and youth control group was lower than that in the gerontic model group [0.62±0.17,0.69±0.14,1.75±0.17,1.11±1.12, (P ＜ 0.05 )].CONCLUSION: High-dose and middle-dose Yufeng capsule is able to decrease the content of TXB2 and increase the content of 6-keto-PGF1 α, and improve their ratio. It is important to enhance the balance of TXB2 and 6-keto-PGF1 α. The effect in the low-dose Yufeng capsule group is lower as compared with that in the high-dose and middle-dose Yufeng capsule groups. It is thought that the low-dose Yufeng capsule has preventive effect.