Protective Effects Of Acanthopanax Senticosus Saponins On Acute Incomplete Cerebral Ischemia In Rats

Cerebral ischemic disease is one of the top life-threatening conditions at present, the mobility of cerebral ischemic emergency becomes of increasing trend while people are growing old .So it is the urgent duty for people to develop the safe and effective drugs to protect the brain from ischemia. Acanthopanax senticosus saponins (ASS) are the aggregate of 16 kinds of saponins extracted from leaves of Acanthopanax senticosus .Some evidences obtained with animal models and clinical studies have demonstrated that ASS act as portective-therapectic effects of neuron injury ,cerebral and myocardial infarction .But ASS are still in need of an detailed integrity of research on the therapeutic mechanism of cerebral ischemic disease .In this paper ,the effects of ASS on cerebral ischemia were investigated in a acute incomplete cerebral ischemic (AICI) model in rats.50 Wistar rats were divided into 5 groups randomly including the Sham group, model group, ASS 25mg/kg group, ASS 50mg/kg group and KuDiezi Injection(KDZI) group(25mg/kg) . Blank group and model group were only administrated by ip with physiologic saline, and KDZI group was used as a positive control. The other groups were treated by ip with drugs.Animals were pretreated for 3 days with drugs. 0.5 hour after the ending time of administering, rats were anesthetized by intraperitoned injection of 3.5ml/kg kessodrate. The bilateral conmen carotid arteries were ligated. After 3 hours, blood samples were put in heparin and 3.8% sodium citrate solution (9:1v/v) used for the assay of blood viscosity , the ratio of platelet adhesion and platelet aggregation. Blood viscosity was examined with LBY-N6A viscometer within low shear rate (10/s),middle shear rate (80/s)and high shearrate (160/s).The ratio of platelet adhesion was examined with LBY-F5 platelet adhesion instrument, according to the formula: Platelet adhesion ratio= (the numbers before adhesion-the numbers after adhesion) / the number before adhesion. Collect the blood serum sample for the assay of the activities of SOD and NO, the content of MDA and NOS.The animals were sacrificed by exsanguinations and decapitation, the brain was immediately taken out and cerebrum was separated from other parts. Weighed its wet weight to count the cerebral index. Then separated the cerebrum upsides. The left hemisphere was weighed and put it into 110℃oven to be roasted to constant weight, then weighed the dry tissue, cerebral water content was measured by the simple dry-wet method. The right part were weighed and homogenized ,for the assay of SOD, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, Ca²⁺ and MDA content.The results showed that ASS decreaseηB remarkably, not only lessen low shear rateηB which is proportional to erythrocyte aggregation, but also decrease the middle and high shear rateηB. High shear rate blood viscosity mainly due to erythrocyte deformability. Platelet aggregation and adhesion is very important in thrombosis formation. The balance between vessel wall PGI2 production and platelet TXA2 production has been postulated to play an important role in regulating platelet aggregation and adhesion. When AICI appears the balance was damaged, which improved platelet aggregate and adhese. ASS can inhibit platelet adhesion and aggregation,prevent platelet-rich thrombus from formation, so protect the brain tissue indirectly. In cerebral ischemia: ATP exhaustation induce ion pump dysfunction, so cell membrane depolarizate, EAA is released remarkably. EAA act with its receptor induce agreat of Ca²⁺ influx, making cellular Ca²⁺ overload .Calcium is now widely implicated as having a deleterious role in ischemic brain damage. Comparing with the cerebral ischemic rats, the effect of ASS on Ca²⁺ content of brain tissue is reduced remarkablely, which stop Ca²⁺ overload. ASS enhance Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, stop the depletion of energy. ASS can increase the SOD activity, and decrease the MDA content which protect brain tissue from damage of oxygen free radicals. Because of the restraint of EAA and Ca²⁺ acted by ASS, the activity of nNOS, iNOS reduced remarkably. As a result, ASS reduce NO injury which encounter cerebral ischemia, showing the ability of neron-protective effect. ASS also reduce cerebral index and cerebral water content weakening inflammatory response and lessening encephaledema.In summary, ASS's protective mechanism is definite as fellows. ASS decrease erythrocyte aggregation, enhance erythrocyte deformability and prev- -ent platelet-rich thrombus from formation. So the blood circulation is improved, protecting the brain tissue indirectly. ASS protect the brain tissue from damage of oxygen free radicals, Ca²⁺ overload and NO injury. ASS stop the depletion of energy showing the ability of neron-protective effect. ASS also weaken inflammatory response and lessen encephaledema.From the experiment enunciation above, we can get the conclusion that the ASS can resist to lack brain harm, improve cerebral ischemic appearance, showing an explicit brain a protection. The foreground of Ass is outstanding in the aspects of preventing and curing cerebral disease...