642 中国药理学与毒理学杂志 2012 年 10 月第 26 卷第 5 期 Chin J Pharmacol Toxicol,Vol 26,No 5,Oct % mg kg h 1. 3 HPD % 6

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1 观察人参总皂苷 ( EPG) 和丹参总酚酸 ( ESM) 配伍对急性血瘀模型大鼠血液流变性的影响大鼠按分组分别 ig 给予 EPG 200 mg kg - 1,ESM 200 mg kg - 1,EPG 200 mg kg ESM 200 mg kg - 1 和阿司匹林 100 mg kg - 1 ( 阳性对照 ), 每天早晚各 1 次, 共 7 次第 5 次给药后, 大鼠再 sc 给予肾上腺素加冰浴造成急性血瘀模型锥板法测定全血黏度和血浆黏度 ; 光电比浊法测定二磷酸腺苷 ( ADP) 诱导的血小板聚集 ; 光电电磁法测定凝血参数与正常对照组相比, 模型组大鼠全血黏度和血浆黏度升高, 血小板最大聚集率显著增加, 纤维蛋白原 ( Fib) 含量显著增加, 凝血酶时间 ( TT) 活化部分凝血活酶时间 ( APTT) 和凝血酶原时间 ( PT) 均显著缩短 ( P < 0. 01) 与模型组相比, 单独应用 EPG 和 ESM 均能显著降低全血黏度和血浆黏度, 显著降低 Fib 含量, 显著延长 APTT, 其中 EPG 还能明显延长 PT 和 TT,ESM 还能显著降低血小板最大聚集率与单独应用 EPG 或 ESM 相比,EPG 与 ESM 配伍组能进一步改善血液流变学指标, 在降低血小板最大聚集率方面显著优于单用 EPG( P < 0. 05), 在延长 TT 方面显著优于单用 ESM( P < 0. 05), 在降低 Fib 含量方面显著优于单用 EPG 或 ESM( P < 0. 05) 与阳性对照阿司匹林相比, 单用 EPG 或 ESM 对血液流变性的改善作用不及阿司匹林, 但 EPG 与 ESM 配伍对血液流变的改善作用与阿司匹林相似, 但无统计学差异 EPG 和 ESM 单用能显著改善血瘀模型大鼠血液流变的异常, 且二者配伍后能进一步增强对血瘀模型大鼠血液流变的改善作用人参总皂苷 ; 丹参总酚酸 ; 血液流变学 ; 血瘀 ; 血小板聚集 ; 全血凝固时间 ; 纤维蛋白原 R285 R973 DOI /j. issn A ADP fibrinogen Fib 4-6 saponins of Panax ginseng EPG 1-2 phenolic acids of Salvia miltiorrhiza ESM Rb 3 EPG ESM vip com Tel Fax EPG

2 642 中国药理学与毒理学杂志 2012 年 10 月第 26 卷第 5 期 Chin J Pharmacol Toxicol,Vol 26,No 5,Oct % mg kg h 1. 3 HPD % mg kg - 1 EPG 60% 60% 200 mg kg -1 ESM 200 mg kg -1 EPG 200 mg kg -1 + EPG Rg % ESM 200 mg kg -1 ig Re 4. 13% Rg % ig Rb % Rc 6. 83% Rb % Rb % Rd 2. 55% sc 1. 2 ESM 16 ~ 18 h cm min 80 1 h 6 20 ku L % h V /V APTT TT PT Fib ~ % 80% h ~ AB ml 5 40% s -1 erythrocyte aggregation index EAI EAI = η a1 /η a100 η a1 1 s η a s ~ ml 3000 g 15 min 0. 8 ml 37 ESM B 41. 5% 2. 32% % 4. 53% 1. 91% 2 ml 800 g 10 min BTA6E93 10 mg L g 10 min L - 1 ADP μmol L - 1 thrombin time TT 37 activated partial thromboplastin APTT 1. 6 APTT TT PT Fib prothrombin time PT Fib 1 ml 3000 g 15 min 37 APTT TT PT LG-R-80B Fib TGL-16G A F-2 x 珋 ± s SPSS t 1. 2 Sprague-Dawley SD 240 ~ g SCXK sc 2. 1 EPG ESM 0. 8 mg kg h 1 sc 0. 8 mg kg h min 2 h 2 sc s - 1

3 643 Tab. 1 Effect of extract of P. ginseng saponins EPG and S. miltiorrhiza phenolic acids ESM alone or in combination on whole blood and plasma viscosity in rats with blood stasis Group Whole blood viscosity / mpa s s - 1 Viscosity of plasma / mpa s 50 s - 1 Normal control 4. 2 ± ± ± ± ± Model 4. 9 ± 0. 4 ** 5. 3 ± 0. 5 ** 5. 9 ± 0. 5 ** ± 2. 8 ** ± ** Aspirin 4. 4 ± 0. 2 ## 4. 5 ± 0. 5 ## 5. 2 ± 0. 5 ## ± 3. 6 ## ± ## EPG 4. 4 ± 0. 3 # 4. 9 ± 0. 5 # 5. 4 ± 0. 5 # ± 3. 6 # ± ## ESM 4. 3 ± 0. 3 ## 4. 6 ± 0. 6 ## 5. 3 ± 0. 5 ## ± 3. 9 ## ± ## EPG + ESM 4. 2 ± 0. 5 ## 4. 5 ± 0. 4 ## 5. 2 ± 0. 6 ## ± 3. 4 ## ± ## The rats in aspirin EPG ESM and EPG + ESM groups were ig given aspirin 100 mg kg - 1 EPG 200 mg kg - 1 ESM 200 mg kg - 1 and EPG 200 mg kg ESM 200 mg kg - 1 twice a day for 7 times. After the 5th administration the blood stasis rat model was induced by ice water soaking for 5 min during the time interval between two subcutaneous injection of epinephrine. The rats were fasted overnight and the blood sample was collected after the last administration. The whole blood viscosity and plasma viscosity were measured. x 珋 ± s n = 10. ** P < compared with normal control group # P < ## P < compared with model group. P < EPG ESM EPG 200 mg kg - 1 ESM 200 mg kg - 1 EPG 200 mg kg - 1 ESM 200 mg kg P < P < Fib APTT TT PT EPG ESM EPG ESM P < EPG 200 mg kg - 1 Fib APTT PT TT P < 2. 2 EPG ESM ESM 200 mg kg - 1 Fib 2 Tab. 3 Effect of EPG and ESM alone or in combination on fibrinogen Fib activated partial thrombin time APTT P < thrombin time TT and prothrombin time PT in rats EPG 200 mg kg - 1 with blood stasis ESM 200 mg kg - 1 EPG Group ESM P < Normal control Fib /g L ± 0. 3 APTT /s ± 4. 3 ESM EPG ESM Model 5. 0 ± 0. 6 ** ± 3. 5 ** EPG EPG Aspirin 4. 3 ± 0. 6 # ± 3. 3 ## ESM P < ESM 4. 4 ± 0. 5 # ± 3. 2 # EPG 4. 4 ± 0. 4 # ± 1. 8 # Tab. 2 Effect of EPG and ESM alone or in combination on platelet maximum rate in rats with blood stasis Group Maximum platelet aggregation /% Normal control ± 4. 0 Model ± 4. 6 ** Aspirin ± 5. 0 ## EPG ± 5. 2 ESM ± 4. 3 ## EPG + ESM ± 4. 7 ## See Tab. 1 for the treatments. x 珋 ± s n = 10. ** P < compared with normal control group # P < ## P < compared with model group P < compared with EPG alone group. ESM + EPG 3. 3 ± 0. 8 ## ± 3. 1 ## Group TT /s PT /s Normal control ± ± 2. 6 Model ± 4. 4 ** ± 1. 3 ** Aspirin ± 4. 5 ## ± 2. 9 # ESM ± ± 4. 4 EPG ± 3. 4 # ± 3. 9 # ESM + EPG ± 3. 8 ## ± 3. 4 # See Tab. 1 for the treatments. 珋 x ± s n = 10. ** P < compared with normal control group # P < ## P < compared with model group P < compared with ESM alone group P < compared with EPG alone group.

4 644 中国药理学与毒理学杂志 2012 年 10 月第 26 卷第 5 期 Chin J Pharmacol Toxicol,Vol 26,No 5,Oct 2012 APTT P < PT TT Fib EPG ESM EPG ESM EPG ESM EPG + ESM Fib P < EPG ESM EPG ESM Fib APTT TT 3 EPG ESM EPG ESM Fib Fib Fib 1 Zhang TJ. Modern Experimental Methods in Pharmacology M. Beijing United Pub- Fib lishing House of Beijing Medical College and Peking Union Medical College Gao SH Dong RS. Silent myocardial ischemia SMI and microcurculation-hemorheology J. Chin J Hemorh He XX Xu HL Yu XF Qu SC Sui DY. Effects of ginsenoside-rb on platelet aggregation and hemorheology 2 in rats of acute blood stasis model J. Chin Pharmacol Bull Hu WP Li XM Chang HL Li LZ. Effect of Radix Salvia miltiorrhiza on the hemorrheological characteristics in stressful rats J. J Chin Microcirc APTT PT 5 Chen LN Zhu XX. Advances in study of the pharmacological effects of Danshen on hemorheology J. China J Chin Mater Med Wang CS Yang JR Gui CQ Ding BP Song JG. Effects of Salvia miltiorrhiza injection on acute myocardial ischemia and hemorheology models of rat J. Chin J Fib Clin Pharmacol Ther Chen Q. Research Methods in Pharmacology of Chinese APTT TT PT EPG Medicine Media M. Beijing ESM People's Medical Publishing House Fib 8 He L Jiang WY Mao TM. Preliminary exploration on APTT ESM establishing a simulated model of acute and chronic af- blood stasis by adrenaline EPG TT PT EPG + ESM ter-qi-stagnation injection EPG ESM EPG TT ESM J. Chin J Integrated Tradit West Med

5 645 Ameliorative effect of Panax ginseng saponins combined with Salvia miltiorrhiza phenolic acids on hemorheological abnormality in rats with acute blood stasis ZHANG Ke 1 MA Xu 1 2 HAN Shu-yan 1 3 MA Zhi-zhong 1 TU Peng-fei 1 1. State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing Beijing China 2. Patent Examination Cooperation Center State Intellectual Property Office China 3. School of Oncology Beijing Cancer Hospital & Institute Key Laboratory of Carcinogenesis and Translational Research Ministry of Education Peking University Beijing China Abstract OBJECTIVE To evaluate the effect of Panax ginseng saponins EPG combined with Salvia miltiorrhiza phenolic acids ESM on hemorheological abnormality in rats with acute blood stasis. METHODS The rats were randomly divided into normal control model EPG 200 mg kg - 1 ESM 200 mg kg - 1 EPG 200 mg kg ESM 200 mg kg - 1 and aspirin 100 mg kg - 1 positive groups. The rats were ig given corresponding drugs twice a day for consecutive 7 times. After the fifth administration the rats were sc given epinephrin in ice water soaking to set up the acute blood stasis model. Whole blood viscosity and plasma viscosity were evaluated by coneplate viscometer hematocrit determined by micro-capillary method platelet aggregation measured by photoelectric turbidimetry and coagulation parameters evaluated by optical electromagnetic method. RESULTS Compared with normal control group whole blood viscosity and plasma viscosity of rats in blood stasis model group significantly increased the maximum platelet aggregation rate was also remarkably elevated. Also fibrinogen Fib content increased while prothrombin time PT activated partial thrombin time APTT and thrombin time TT decreased P < Compared with model group EPG 200 mg kg - 1 or ESM 200 mg kg - 1 alone could obviously decrease whole blood viscosity plasma viscosity and Fib content but significantly delay APTT P < P < Meanwhile EPG 200 mg kg - 1 significantly delayed PT and TT. ESM 200 mg kg - 1 significantly inhibited the epinephrin-induced platelet maximum aggregation rate. Compared with EPG or ESM alone group EPG 200 mg kg ESM 200 mg kg - 1 ameliorated the hemorheological abnormality further in rats with acute blood stasis as revealed by the greater platelet maximum aggregation inhibition P < vs EPG more delayed TT P < vs ESM and increased Fib content P < vs EPG or ESM. Compared with aspirin group EPG and ESM showed less inhibition on platelet aggregation while EPG + ESM exerted similar hemorheological improvement to aspirin but there was no statistical significant difference. CONCLUSION The combination of EPG with ESM improves the hemorheological abnormality in rats with acute blood stasis more powerful than EPG or ESM alone. Key words saponins of Panax ginseng phenolic acids of Salvia miltiorrhiza hemorheology blood stasis platelet aggregation whole blood coagulation time fibrinogen Foundation item The project supported by National Science Fund for Distinguished Young Scholars of China Corresponding author TU Peng-fei pengfeitu@ vip com Tel Fax

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