| BackgroundICH is a worldwide common disease, frequently-occurring disease. Both mortality and disability rateare high, which influences the patient’s health and quality of life seriously. In recent years, more researchfocus on the mechanism of injury after cerebral hemorrhage at China and abroad, and research on thrombinhas been a hot issue. Argatroban, is the only direct thrombin inhibitor, only acts on the active site tothrombin, and combines with thrombin speedily. Clinical curative effect of argatroban is better, which isbetter than that of several other clinical use of thrombin inhibitors.Nitric oxide (NO) in the human body is generated mainly by nitric oxide synthase (NOS) catalytic L–arginine. The role of NO in the body dependent on its available concentration. Physiological concentrationof NO in the body plays a variety of biological effects, while high concentrations of NO has a variety ofharm to the human body. NOS includes constitutive NOS (cNOS) and inductive NOS (iNOS). Undernormal circumstances, iNOS does not express in brain tissue. But in pathological conditions, such ascerebral hemorrhage, iNOS can be induced and express in brain tissue, and in turn, produce a lot NO, cause harm to human body. The study of experimental rats find that rats knock out iNOS gene or choose iNOSinhibitor can reduce ischemic brain damage, which suggest iNOS may play an important role in ICH rats.AimsTo investigate the effect of Argatroban to reduce the brain water content of brain tissue，BBBpermeability and to improve the neurologic defecit score and to effect the expression of iNOS inexperimental ICH model of rats,that in order to elucidate the mechanisms of iNOS and the effect ofArgatroban intravenously to the perihematomal brain tissue．Methods1. Male SD rates were randomly divided into three groups, including control group, cerebral hemorrhagegroup and argatroban treatment group.2. The rats were anesthetized intraperitoneally, and fixed in the stereotaxic apparatus. In cerebralhemorrhage group and argatroban treatment group: rats were received an intracerebral injection of60ulantologous blood. In control group: rats had only a needle isertion. On the third hour after modelestablished successly, rates in argatroban treatment group were received an argatroban injection through tailvein every24h, and rats in control group and cerebral hemorrhage group were received an sterile saline(1mg/Kg) injection through tail vein every24h.3. The perihematomal brain tissue sampies were extracted on the ICH6h,12h, ld,3d,5d,7d, respectivelyto determine the differential expression of iNOS mRNA and protein by immunohistochemical, RT-PCR andWestern Blot methods. The rat’s water content of brain tissue, BBB permeability and neurologic defecitscores were also observed．4. Datas ate analyzed by using SPSS16.0statistic software pack, and are showed as mean values±standard deviation (x s). Mono-factor analysis of variance (ANOVA) is used to test difffence amonggroups, and multiple comparison by using SNK.0.05Results1. Argatroban group got higher Cacia scores than that in cerebral hemorrhage group at every time pointsrespectively. Argatroban group got nearly normal scores on5thand7th．There were significant differencbetween the argatroban group and the cerebral hemorrhage group on12hour,1st, and3rd(P<0.05), and between the cerebral hemorrhage group and the control group at every time points(P<0.05).2. The water content of brain tissue in cerebral hemorrhage group were much higher than that in controlgroup(P<0.05)，it began to rise at6h，peaked on days1and3, and then declined on day5gradually，stillhigher on7th. Argatroban group got much brain water content than that in control group, but less than thatin cerebral hemorrhage group on12hour,1st, and3rd, and5th, respectively (P<0.05)．3.The content of EB in cerebral hemorrhage group was much higher than that in control group at each timepoints, and the content of EB in argatroban group was much lower than that in control group on12hour,1st,and3rd. The content of EB in argatroban group was much lower than that in cerebral hemorrhage group on12hour,1st, and3rd(P<0.05).4.The expression of iNOS mRNA and protein of argatroban group was higher than that of control group on6hour,12hour,1st, and3rd, and on12hour,1st,3rd, and5th, respectively(P<0.05). The expression of iNOSmRNA and protein of cerebral hemorrhage was higher than that of control group at each time points, andon12hour,1st,3rd,5th, and7th, respectively(P<0.05).Conclusions1. Argatroban could reduce the brain water content of brain tissue，BBB permeability and improve theneurologic defecit score.2. Argatroban-induced cerebral edema clearance was correlated with the down-regulation of iNOSexpression of mRNA and protein in perihematomal area．That may be one of the mechanisms ofArgatroban to brain edema clearance. |
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