| Abstract:Objective:To observe the effect of Zhilong Huoxue Tongyu capsule (ZHTC) on thrombosis and inflammatory injury in cerebral ischemia injury rats and discuss the mechanism. Methods:150 male SD rats (another 30 male rats were spare) were randomly divided into six groups:treatment groups including high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group, control group(Buchang Naoxin Tong capsule group), model group and sham-operation group, each group contained 25 rats. Rats of each treatment groups were feed with ZHTC 1.6 gram per kilo per rat,0.8 gram per kilo per rat,0.4 gram per kilo per rat, Buchang Naoxin Tong capsule(BNTC) 0.8 gram per kilo per rat, rats of model group and sham-operation group were feed with normal saline.After 7-day-feeding with drugs, the model of focal cerebral ischemia in rats was made by right common carotid artery ligation which could induce middle cerebral artery occlusion. After 24 hours, evaluated nervous system symptom by "5 score standard". (1) collected blood from abdominal aorta, measured the content of IL-1 IL-10,NOS in serum by ELISA; (2) quickly removed the thread in the polyethylene pipe between the right total carotid artery and left carotid vein, measured the weight of thrombus. (3) removed brains, stained brain tissue sections by TTC, measured area of cerebral infarct by image analysis. Results:(1) The common situation and nervous system symptom in focal cerebral ischemia rats. Rats of sham-operation group, their fur were luster, their actions were agility, their feeding were nomal, and their response to the environment changes was sensitive, they did not appear neurological defect symptom. Rats of the model group, their fur gradually lost luster, their spirit state were low, movements and feeding were reduced, they obviously appeared neurological defect symptom, such as turned around the paralyzed side, dumpage even could not stand up, etc; Rats of high dose ZHTC group, moderate dose ZHTC group, low dose ZHTC group and control group, after the treatment, their fur were luster, their feeding were nomal, their spirit state and their movement resumed rapidly, their neurological defect symptom improved, only the opposite side forelimb could not entirely stretch, a few rats turned around the paralyzed side or appeared dumpage, etc. The nervous system symptom score of model group rats were much higher than that of sham-operation group rats(P<0.01); Compared with the model group, the nervous system symptom score of high dose ZHTC group,moderate dose ZHTC group and control group significantly decreased(P<0.01), low dose ZHTC group also decreased in some degree (P＜0.05); Compared with the low dose ZHTC group, the nervous system symptom score of high dose ZHTC group,moderate dose ZHTC group and control group significantly decreased, it had significantly difference(P<0.01); Multiple comparisons of high dose ZHTC group,moderate dose ZHTC group and control group, it had no significantly difference. (2) The effects of ZHTC on inflammatory cytokines for rats. Compared with the sham-operation group, the content of IL-1 in serum of model group,high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group rats significantly increased (P<0.01).Compared with the model group, the content of IL-1 in serum of high dose ZHTC group,moderate dose ZHTC group and control group significantly decreased (P＜0.05) while the low dose ZHTC group didn't have significantly difference;Multiple comparisons of IL-1 content of high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group, it didn't have significantly difference. Compared with the sham-operation group, the content of IL-10 in serum of model group,high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group rats significantly increased (P<0.01或P<0.05).Compared with the model group, the content of IL-10 in serum of high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group significantly increased (P＜0.05); Multiple comparisons of IL-10 of high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group, it didn't have significantly difference. Compared with the sham-operation group, the content of NOS in serum of high dose ZHTC group and control group significantly increased (P＜0.01) while the content of NOS in serum of model group,moderate dose ZHTC group and low dose ZHTC group rats didn't have significantly difference; Compared with the model group, the content of NOS in serum of high dose ZHTC group and control group significantly increased (P＜0.05)while the content of NOS in serum of moderate dose ZHTC group and low dose ZHTC group rats didn't have significantly difference; Compared with the high dose ZHTC group, the content of NOS in serum of moderate dose ZHTC group,low dose ZHTC group significantly decreased (P<0.05);Multiple comparisons of NOS of moderate dose ZHTC group,low dose ZHTC group and control group, it didn't have significantly difference(P>0.05). (3)The effects of ZHTC on thrombosis for rats. The weight of thrombosis of model group,high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group rats were much higher than that of sham-operation group rats (P< 0.05或P<0.01).Compared with the model group, the weight of thrombosis of high dose ZHTC group,moderate dose ZHTC group and control group significantly decreased (P＜0.05) while the low dose ZHTC group didn't have significantly difference; Multiple comparisons of high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group, it didn't have significantly,difference. (4) The effects of ZHTC on the area of cerebral infarct in cerebral tissue of rats. The area of cerebral infarct in cerebral tissue of model group,high dose ZHTC group,moderate dose ZHTC group,low dose ZHTC group and control group rats were much higher than that of sham-operation group rats(P<0.01); Compared with the model group, the area of cerebral infarct in cerebral tissue of high dose ZHTC group,moderate dose ZHTC group and control group significantly increased(P<0.05 or P＜0.01). Although the area of cerebral infarct of low dose ZHTC group rats didn't have significantly difference, it increased by variable degrees; Compared with the low dose ZHTC group, the area of cerebral infarct in cerebral tissue of high dose ZHTC group and control group significantly increased, it had significantly difference(P<0.01) while the moderate dose ZHTC group rats didn't have significantly difference;Multiple comparisons of area of cerebral infarct of high dose ZHTC group,moderate dose ZHTC group and control group,it didn't have significantly difference. Conclusion:(1) ZHTC can significantly improve the evaluating of neurological function defect for middle cerebral artery ischemia injury, reduce the area of cerebral infarct in cerebral tissue. It plays a positive role in cerebral protection. Its mechanism probably relate to inhibit inflammation reaction of ischemia injury by decreasing the IL-1 in serum and increasing the IL-10 content. It is also increasing NOS activity which can increase the NO level which is a kind of vascular endothelial factor, decreasing the thrombosis and improving the micro circulation. All of these play a positive role in cerebral protection. (2)The protective effect of ZHTC for cerebral ischemia rats has a certain dose-effect relationship.
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