| Abstract:Objective: To observe the effect of Zhilong Huoxue Tongyu capsule (ZHTC) on brain water content,nerve cell apoptosis,protease activated receptor-1 and hypoxia-inducible factor 1αin intracerebral hemorrhage rats. Thus further elucidate the injury mechanism of intracerebral hemorrhage and it's possible effects on brain protection. That will provide a theoretical basis for the clinical treatment of cerebral hemorrhage by using ZHTC. Methods: 1. Sectionalization method: 200 male SD rats were randomly divided into five groups: sham-operation group, model group, low dose ZHTC group,moderate dose ZHTC group and high dose ZHTC group, each group contained 40 rats.2. Dosing method: To build mode 1 week before,Rats of each ZHTC treatment groups were feed with ZHTC 0.4 gram per kilo per day,0.8 gram per kilo per day,1.6 gram per kilo per day,rats of model group and sham-operation group were feed with normal saline. 3.Mading model method: Autologous blood was injected into the caudate nucleus of rats,which produced cerebral hemorrhage model by using stereotaxis instrument technique.The sham-operation group inject the volumetric saline. 4.Specimen method: Decapitation was at 6h, 1d, 3d, 7d after the model was produced, and there were ten rats in each group. Among them , five rats were measured brain water content with dry wet heavy approach, five rats were beared internal fixation by heart perfusion to take brain making biopsy. Use TUNEL method for determining the apoptotic cells expression and immunohistochemical method for determining the expression of PAR-1 protein and hypoxia-inducible-1αprotein. Results: 1. The common situation and nervous system symptom: Compared with the sham-operation group, the nervous system symptom scores of model group and give medicine of ZHTC group rats were much higher (P<0.01), except the 7d time points; Compared with the model group, the nervous system symptom score of moderate dose ZHTC group and high dose ZHTC group significantly decreased(P<0.01), except the 7d time points, symptoms disappeared basically , it had no statistical significance compared with model group(P>0.05);low dose ZHTC group also decreased in some degree ,except 1d(P<0.01), other time point difference had no statistical significance (P>0.05); Compared with the low dose ZHTC group, the nervous system symptom score of moderate dose ZHTC group and high dose ZHTC group also decreased in some degree ,but the difference had no statistical significance (P>0.05); Multiple comparisons of moderate dose ZHTC group and high dose ZHTC group, it had no significantly difference (P>0.05).2.The situation of brain water content,apoptotic cell, PAR-1 and HIF-1αexpression: The brain water content,apoptotic cell, PAR-1 and HIF-1αexpression of model group and give medicine of ZHTC group rats began to rise after 6h,1d continued to rise,3d reached to the peak, after 7d began to decline. Compared with the sham-operation group, the differences had statistical significance(P<0.01);Comp- ared with the model group, the brain water content,apoptotic cell and PAR-1 of each ZHTC group significantly decreased (P<0.01), the HIF-1αexpression significantly raised (P<0.01);Compared with the low dose ZHTC group, the brain water content,apoptotic cell and PAR-1 of moderate dose ZHTC group and high dose ZHTC group significantly decreased (P<0.01), the HIF-1αexpression significantly raised (P<0.01); Multiple comparisons of moderate dose ZHTC group and high dose ZHTC group, it had no significantly difference (P>0.05).3.Correlation analysis: the brain water content and the apoptotic cells'expression were positively correlated(r=0.971,P=0.000<0.05),the brain water content and PAR - 1 expression were positively correlated(r=0.988,P=0.000< 0.05),the brain water content and HIF-1αexpression were positively correlated (r=0.901,P=0.000 < 0.05). Conclusion: 1. ZHTC can significantly improve the evaluating of neurological function defect for ICH injury. Its mechanism probably relate to inhibit PAR-1 activation, increase HIF-1αexpression, inhibit cell apoptosis and reduce cerebral edema.So that it can realize the repair of tissue damage. 2.The protective effect of ZHTC for ICH rats has a certain dose-effect relationship.
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