Empirical Study On The Pharmacodynamics Of Zhongfeng Ⅰ Hao Treat For Deficiency Of Qi And Blood Stasis In Ischemic Apoplexy

Ischemic apoplexy is correspondence to cerbral infarction in modern medicine,is one of predominant clinical diseases in gerontism,with characteristics of high incidence,mortality,disability and recurrence.It has posed a serious threat to human health and become one of the three major causes of death with cardiovascular disease, malignant tumour in many country.Therefore it is very profitable work to study the pathophysiology of cerebral ischemia and research and produce the effective druges for ischemic apoplexy.My advisor had been on the base of theory of traditional Chinese medicine, incorporated the research on contemporary pharmacology, composed effective prescription that treated for Deficiency of Qi and Blood Stasis in ischemic apoplexy called ZhongfengⅠHao.The prescription which composed of Pueraria, Astragalus mongholicus, Panax pseudoginseng, Rhubarb and so on.To study mechanism of ZhongfengⅠHao,by theory of traditional Chinese medicine,the mode of Deficiency of Qi and Blood Stasis in ischemic apoplexy was induced by inserting a piece of nylon thread into the MCA.Then observed effects of ZhongfengⅠHao on Deficiencyof Qi and Blood Stasis in ischemic apoplexy in rats.The following experiments were carrid out:⑴effects of ZhongfengⅠHao on nerve behavior;⑵effects of ZhongfengⅠHao on infarct size and pathologic histology;⑶effects of ZhongfengⅠHao on platelet aggregation in rats;⑷effects of ZhongfengⅠHao on thrombogenesis in out-of body rats;⑸effects of ZhongfengⅠHao on whole blood specific viscosity,blood plasm specific viscosity, hematocrit in the model of blood stasis rats.Objective:To observe the effects of ZhongfengⅠHao on the model of Deficiency of Qi and Blood Stasis in ischemic apoplexy in rats about nerves function and cerebral infarct size and pathologic histology;effects of platelet aggregation out-of-body thromb in the experimental rats; effects of hemorheology in the model of blood stasis rats.Methods:1.test method of focal cerebral ischemiaGroup and dosage:fifty operated rats were randomly divided into 5 groups with 10 animals in each group:model control group;ZhongfengⅠHao 1.36g/kg,0.68g/kg,0.34g/kg theree groups;positive control group Buchang Naoxintong 2.10/kg;nomal control,10 animals.Each group is successive administrated or given homo-volume normalsaline one time per day for six days.At the end of the sixth day,all animal were killed and brains were rapidly removed.According to Wangjian who is Professor in An Hui TCM and Nafasawa making and improving Deficiency of Qi and Blood Stasis in cerebral ischemia . Refer to Zea Longa appreciating nerves behavior;effects of infarct size. At the end of the sixth day,all animal were killed and brains were rapidly removed.The infarct volume of brain/volume of whole brain(IV % )was caculated with staining of 2,3,5-triphenyl tetrazolium chloride(TTC). Put the rest into 10% formalin fixation for 16h,and evaporation, paraffin imbedding, microtome section, drum dyeing in HE,inspected by light microscope,observed the change of histomorphology,2.Platelet agglutination testFifty adult Wistar rats ,female and male is average,were randomly divided into 5 groups with 10 animals in each group:noomal control,given isochoric normal saline;the other groups :ZhongfengⅠHao1.36g/kg,0.68g/kg , 0.34g/kg;positive control group :Buchang Naoxintong 2.10/kg.Each group was administered by oral,then one time per day for one week.At the end of the 10th day,carried out anaesthetizing , anticoagulation , getting blood from aorta ventralis,then put it into anticoagulant pipe.Using LBY-NJ PA(platelet aggrega- tion)instrument for determining max packing fraction, then calculating inhibition ratio of PA.3. Out-of-body thrombotestFifty adult Wistar rats ,female and male is average,divided into groups and administrated same so above.After anaesthetizing, getting blood from aorta ventralis,then thrombosis were forming by XSN-12.TO determine the length,humid weight on thrombus,stove them in homeothermia baker for 30min at 64℃and weight.4.Effects of ZhongfengⅠHao on the whole blood viscosity, plasma viscosity,hematocritSixty adult Wistar rats ,female and male is average,were randomly divided into 6 groups with 10 animals in each group:noomal control,given isochoric normal saline;the other groups :ZhongfengⅠHao1.36g/kg,0.68g/kg , 0.34g/kg;positive control group :BuchangNaoxintong 2.10/kg.Each group was administered by oral,then one time per day for 10d.On the 9th ,crarring out modle of blood stasis. Abrosia and watering for 18h,after 30min administered at the next morning ,giving blood from aorta ventralis to measuring whole blood viscosity, plasma viscosity,hematocrit.Results:1.Effects of ZhongfengⅠHao on nerve behaviorIn 24h,modle group visible appeared symptom of nerve injury.Rising the rat,it displayed passibe position, and latero-plegia anterior limb flex on the abdomen or moving at the same side. Had significant deviation compared with sham operated group,indicated animal model successing. Compared with model ,both ZhongfengⅠHao high-group and positive group could improve nerves behavior in rat,the effect of improving nerve injury ,muscle force manifestly argument,difference had statiscal singficance. (p<0.05)2.Effects of ZhongfengⅠHao on infarct size and pathologic histologyThrough TTC for coronal-blade brain tissue, uninfarct was red,infarct was alba, circumscription wasclear.Sham group couldn t measure cerebral ischemia size,model group could display evidenter pallid infarcts focus at right brow lobus parietalis and corpora stiata in rats.ZhongfengⅠHao on cerebral ischemia size was smaller than model group. In higher and middle group, distribution about neure and colloid cell wasn t anomaly in cerebral ischemia,the structure of most neure was non apparent abnormality.3.Effects of platelet aggregation in ratsZhongfengⅠHao(1.36/kg) on ADP antileptic platelet aggregation was visable depressant effect .Maximum agglutination was 36.77%,inhibition ratio was 29.19%, compared with nomal control had significant difference with ZhongfengⅠHao high-group (p<0.05). Difference had significance in positive group(p<0.01).4.Effects of ZhongfengⅠHao on thrombogenesis in out-of body ratsComparec with normal control , ZhongfengⅠHao high-group,middle group and positive group all could improve the length of throm(P<0.05);ZhongfengⅠHao high-group could lessen the dry weight and humid weightof throm,have significant deviation compared with normal control(P<0.05);positive group could lessen the humid weight of throm (P<0.05);the effect of dry weight had not statistically significant(P﹥0.05)。5.Effects of ZhongfengⅠHao on whole blood specific viscosity,blood plasm specific viscosity , hematocrit in the model of blood stasis rats. Consequence indicated: indicatrix of hemortheology had significant deviation between control group and normal control(P < 0.05)。Compared with control group, ZhongfengⅠHao high dose group,positive group could obviously improve hemortheology,degrade blood viscidity,improve erythrocyte fragility,elevate erythrocyte deformability(P < 0.05);had difference in hematoplasma specific viscosity,haemat with middle dose group (P < 0.05)。ConclusionCompared with middle and low dose group ,ZhongfengⅠHao could obviously improve nerve injure and cerebral ischemia side in experiment rats, improve the change of patho-brain tissue in ischemic region,and haveprotection with ischemic brain tissue injure , improve PA and effect thrombogenesis, improve hypercoagulaba- le state in rat.