四种缓解化学药物治疗后骨髓抑制中成药对环磷酰胺所致小鼠血虚模型外周血和骨髓象的影响

Influences of four kinds of Chinese medicines that can relieve marrow restraint after chemotherapy on peripheral blood and bone marrow smear in model mice of hematopenia induced by cyclophosphamide

目的:观察补气养血、健脾益肾的参芪颗粒,补气养血的复方阿胶浆,补气养阴的贞芪扶正颗粒,温肾健髓、益气养阴、生血止血的复方皂矾丸4种中成药对环磷酰胺所致小鼠血虚模型外周血及骨髓象的影响。方法:实验于2005-06/09在河南中医学院药理实验室完成。①选用健康昆明种成年小鼠150只,雌雄不拘。按随机数字表法分为15组,每组10只:高、中、低剂量贞芪扶正颗粒组分别按15,10,5g/kg(20mL/kg)剂量灌胃贞芪扶正颗粒混悬液(主要成分:黄芪、女贞子;甘肃扶正药业科技股份有限公司生产,批号040803);高、中、低剂量复方阿胶浆组分别按10,20,30mL/kg剂量灌胃复方阿胶浆(主要成分:阿胶、熟地黄、党参等;山东东阿阿胶股份有限公司生产,批号050446);高、中、低剂量复方皂矾丸组分别按2.4,1.6,0.8g/kg(20mL/kg)剂量灌胃复方皂矾丸混悬液(主要成分:皂矾、西洋参、海马等;陕西郝其军制药有限责任公司生产,批号041014);高、中、低剂量参芪颗粒组按3,2,1g/kg(0.2mL/10g)剂量灌胃参芪颗粒混悬液(主要成分:人参、黄芪、当归等;江西山高制药有限公司生产,批号040702);鲨肝醇组按10g(20mL)/kg剂量灌胃鲨肝醇混悬液;空白组和模型组灌胃同体积的生理盐水(0.2mL/10g)。每天给药1次,连续给药10d。从实验的第6天开始除空白组外,各组小鼠腹腔注射环磷酰胺40mg/kg,连续给药5d。②各组小鼠分别于末次给药后24h,进行血常规检测。另取右侧股骨,镜下计数骨髓有核细胞数。③计量资料符合正态分布、方差齐者用t检验。结果:小鼠150只均进入结果分析。①对外周血的影响:模型组小鼠血白细胞、红细胞和血小板计数及血红蛋白水平、血细胞比容均明显低于空白组(t=2.49～8.19,P<0.05￣0.01)。鲨肝醇组、各剂量参芪颗粒组和复方阿胶浆组及贞芪扶正颗粒组、复方皂矾丸组小鼠血白细胞计数均明显高于模型组(t=3.67～9.12,P<0.01)。中剂量复方阿胶浆组、贞芪扶正颗粒组和复方皂矾丸组和高剂量贞芪扶正颗粒组小鼠血红细胞计数明显高于模型组(t=2.58～3.05,P<0.05￣0.01)。高、中剂量复方阿胶浆组和中、低剂量贞芪扶正颗粒组小鼠血血小板计数明显高于模型组(t=2.48～2.84,P<0.05￣0.01)。各剂量复方阿胶浆组和各剂量贞芪扶正颗粒组和中、低剂量复方皂矾丸组小鼠血血红蛋白水平明显高于模型组(t=2.21～3.28,P<0.05￣0.01)。中剂量参芪颗粒组、各剂量复方阿胶浆组、高剂量贞芪扶正颗粒组,以及高、中剂量复方皂矾丸组小鼠血细胞比容明显高于模型组(t=2.15～2.86,P<0.05)。②对骨髓象的影响:与空白组比较,模型组小鼠骨髓有核细胞数均明显低于空白组(t=8.08,P<0.01)。鲨肝醇组,各剂量参芪颗粒组、复方阿胶浆组、贞芪扶正颗粒组、复方皂矾丸组小鼠骨髓有核细胞数明显高于模型组(t=3.05～5.67,P<0.01)。结论:参芪颗粒、复方阿胶浆、贞芪扶正颗粒、复方皂矾丸对环磷酰胺所致小鼠血虚模型外周血血细胞状况和骨髓象均有改善作用;其中贞芪扶正颗粒和复方皂矾丸对白细胞计数、红细胞计数的升高作用为优;贞芪扶正颗粒和复方阿胶浆对血小板计数升高作用为优;贞芪扶正颗粒、复方阿胶浆和复方皂矾丸对血红蛋白升高作用为优;4种中成药对血虚模型血细胞比容的影响相近;贞芪扶正颗粒对血虚模型有核细胞的升高作用为优。

AIM： To observe the influences of Shenqi granule that can invigorate vital energy, nourish blood, invigorate the spleen and tonify kidney, compound E Jiao slurry that can invigorate vital energy and nourish blood, Zhenqi Fuzheng granule that can invigorate vital energy, nourish yin, and compound Zaofan pill that can warm kidney, strengthen marrow, supplement qi and nourish yin, have the effects of hematosis and hemostasia on peripheral blood and bone marrow smear in model mice of hematopenia induced by cyclophosphamide. METHODS： The experiment was accomplished at Pharmacology Laboratory of Henan University of Traditional Chinese Medicine from June to September 2005. （1）Totally 150 healthy Kunming adult mice of either sex were selected and randomly divided into 15 groups with 10 mice in each. Mice of high, moderate and low dose of Zhenqi Fuzheng granule groups were given 15,10,5 g/kg （20 mLIkg）Zhenqi Fuzheng granule suspension （main component： radix astragali, glossy privet fruit, produced by Gansu Fuzheng Pharmacy Co., Ltd. Lot number 040803） by gastric perfusion. Mice of high, moderate and low compound E Jiao slurry groups were given 10,20,30 mL/kg compound E Jiao slurry （main component： eguus asinus, prepared rehmannia root, radix codonopsitis, produced by Shandong Dong-E E-jiao Co., Ltd. Lot number 050446） by gastric perfusion. Mice of high, moderate and low compound Zaofan pill groups were given 2.4, 1.6,0.8 g/kg （20 mLIkg）Zaofan pill suspension （main component： melanteritum, panax quinquefolium L., seahorse, produced by Shaanxi Haoqijun Pharmacy Limited-liability Company, lot number 041014） by gastric perfusion. Mice of high, moderate and low Shenqigranule groups were given 3,2,1 g/kg （0.2 mL/10 g）Shenqigranule suspension （main component： ginseng, radix astragali, angelica, produced by Jiangxi Shangao Pharmacy Co., Ltd. Lot number 040702） by gastric perfusion. Mice of Shaganchun group were given 10 g （20 mL）/kg Shaganchun suspension by gastric perfusion. Mice of blank group and model group were given saline of the same volume （0.2 mL/10 g） by gastric perfusion, once a day for 10 days successively. Except the blank group, mice in other groups received 40 mg/kg cyclophosphamide by intraperitoneal injection for 5 days successively from the 6^th day. （2）Blood test was conducted 24 hours after the last administration in mice of each group. Right femoral bone was obtained to calculate karyocyte number under microscope. （3）Measurement data met normal distribution. Those with homogeneous variance received t test. RESULTS： Totally 150 mice were involved in the result analysis. （1）influence on peripheral blood： Counts of white blood cells, red blood cells and platelet, level of haemoglobin and haematocrit in model group were significantly lower as compared with the blank group （t =2.49-8.19,P 〈 0.05-0.01 ）. Count of white blood cells in the Shaganchun group, high, moderate and low Shenqi granule groups, compound E Jiao slurry groups, Zhenqi Fuzheng granule groups and compound Zaofan pill groups were obviously higher than those in the model group （t =3.67-9.12,P 〈 0.01 ）. Count of red blood cells in the moderate compound E Jiao slurry group, Zhenqi Fuzheng granule group, compound Zaofan pill group and high Zhenqi Fuzheng granule group were markedly higher than that of model group （t =2.58-3.05,P 〈 0.05- 0.01 ）. Counts of platelet in high and moderate compound E Jiao slurry groups and moderate and low Zhenqi Fuzheng granule groups were remarkably higher than those of model group （t =2.48-2.84,P 〈 0.05-0.01 ）. Levels of haemoglobin in the high, moderate and low compound E Jiao slurry groups and Zhenqi Fuzheng granule groups and moderate and low compound Zaofan pill groups were significantly higher than those of model group （t =2.21-3.28,P 〈 0.05-0.01 ）. Haematocrits in moderate Shenqi granule group, high, moderate and low compound E Jiao slurry groups, high Zhenqi Fuzheng granule group and high and moderate compound Zaofan pill group were obviously higher than that in the model group （t =2.15-2.86,P 〈 0.05）. （2）influence on bone marrow smear： Compared with the blank group, karyocyte number in the model group was markedly lower （t =8.08,P 〈 0.01 ）. Karyocyte numbers in the Shaganchun group, high, moderate and low Shenqi granule groups, compound E Jiao slurry groups, Zhenqi Fuzheng granule groups and compound Zaofan pill groups were remarkably higher than that in the model group （t =3.05-5.67, P 〈 0.01 ）. CONCLUSION： Shenqi granule, compound E Jiao slurry, Zhenqi Fuzheng granule and compound Zaofan pills can improve the white blood cells and bone marrow smear in mice model of hematopenia induced by cyclophosphamide. Zhenqi Fuzheng granule and compound Zaofan pills have better effect on increase of white blood cells and red blood cells. Zhenqi Fuzheng granule and compound E Jiao slurry have better effect on counting increase of platelet. Zhenqi Fuzheng granule, compound E Jiao slurry and compound Zaofan pill have better effect on level increase of haematoglobin. The effects of four kinds of medicine on haematocrit in models of hematopenia are similar. Zhenqi Fuzheng granule has better effect on karyocytes in model mice of hematopenia.