The Protective Effect And Mechanism Of Kang Naoxueshuan Tablet Against Ischemia Injury

Background and purpose Ischemia cerebral injury is also named stroke by traditional chinese physician. And the experience in treating this kind disease has been accumulated in the long history of the applicant of the traditional chinese medicine. Complex reasons cause angiostegnosis and the abnormity of blood rheology , whereafter induce the blood siltation and thrombogenesis, in the ultimate the cerebral infarction is formed. That is the main pathomechanism of ischemia cerebral injury. Kang Naoxueshuan Tablet(KNT), which is composed by many chinese crude drug and extracted through advanced technology, can treat presymptom of stroke and cerebral thrombosis.And its complex moity have been proved effective to antipatelt,anticoagulated blood and suppress thrombogenesis. In this thesis ,we applied the focal cerebral ischemia model by Middle cerebral artery occlusion (MCAO) in rat, observed the protective effect and approached the machnism of KNT againt ischmia cerebral injury. Our aim is to get more experimental evidance to support the exploitation and application of the compound preparation.Methods1. Focal cerebral ischemia model in rat was induced by transient occlusion of the middle cerebral artery . After MCAO, evaluated neurological deficit score in 3h,6h and 24h, and sacrificed rats after 24h to measure infarct volum.Observed effect of different dosage suspension of KNT on improving neuromotor function and reducing brain infarct volum in rat.2. Formed the bypass between arteria cervicalis and vena cervicalis, and prepared the vitro-thrombus in rats by thread-embolism method. Weighed the thrombus in dry and wet status respectively. Observed the effect of KNT suspension on thrombus dry and wet weight.3. To get the anticoagulated blood through arteria cervicalis cannula in rats, evaluated effect of different dosage suspension of KNT on blood platelets count and aggregation of platelet, and effect on HCT,PV and WBV.In the model of MCAO and vitro-thrombus, the rats were divided into the model(or control) group,positive group,crude drug group and treating group. Model(or control) group was given equal volume NS; positive group was given XiaoShuantong Tablet(included by Chinese pharmacopoeia); crude drug group was given dry extract of KangNaoxueshuan Tablet; treating group was divided into three groups (low,middle and high dosage).Every group was given drug by intragastric administration according volum.Results1. Visible neuromotor dysfunction has been emerged after cerebral ischemia in model group, and the symptom was aggravated when ischemia time was extended, neurological deficit score 3h, 2.80±1.3,6h, 3.00±1.33,24h, 3.56±1.5. Compared to model group, treating group could improve neurological symptom and the effect was dose- dependent, neurological deficit score was: low dosage, 3h, 1.44±0.53,6h, 1.56±0.53,24h, 1.67±0.87(P<0.01); middle dosage, 3h, 1.10±0.57,6h, 1.30±0.48,24h, 1.40±0.69(P<0.01); high dosage, 3h, 0.90±0.44,6h, 1.00±0.71,24h, 1.30±0.53(P<0.01).After 24h cerebral ischemia, infarce volume of model group was (27.51±4.71)%, and compared to model group , treating group could reduced infarct volume: low dosage, 3h, (15.37±7.21)% (P<0.01),middle dosage, (14.60±7.00)%(P<0.01),high dosage, (11.18±3.35)% (P<0.01).2. Treating group could reduce the dry and wet weight of vitro-thrombus, and the effect was dose -dependent. Compared to thrombus dry weight of model group: 4.93±2.17mg,low dosage: 3.35±1.44mg,middle dosage: 3.13±1.38mg(P<0.05); high dosage: 2.88±1.02mg(P<0.05).Thrombus wet weight of model group: 24.23±8.21mg,low dosage: 15.56±5.13mg(P<0.05), middle dosage: 12.26±3.55mg,(P<0.01), high dosage:11.08±3.10mg(P<0.01).3. Compared to control group, high dosage of KNT could impress platelet aggregation which induced by ADP, the 1,3,5 minute PAG and MPAG were: (40.24±12.9)%,(43.08±5.44)%,(56.43±7.93)% and (42.13±8.45)%(P<0.01). Middle dosage could reduce 1min PAG(P<0.05)and low dosage hadn't obvious effect. Only high dosage could decrease blood platelets count(P<0.05), but middle and low dosage hadn't obvious effect.4. Outstanding effect to HCG and PV wasn't observed. But compared to control group, middle dosage could reduce (36.03±5.45)%,(41.41±7.71)% and (32.97±6.17)%(P<0.01)of normal WBV which in 37.5/s,90/s and 300/s shear rate respectively , and high dosage could reduce (30.31±11.44)%,(35.51±8.37)% and (19.84±3.80)%(P<0.05)of normal WBV.Conclsion The results presented here showed that KNT could improve neuromotor function and reduce infarct volume after cerebral ischemia, and displayed various effect against ischemia injury. The mechanism might be related to the effect on reducing WBV,repress platelet aggregation and interfer thrombogenesis.