Improving Effects of Argatroban on the Brain Damage of Model Rats with Cerebral Hemorrhage / 中国药房

ABSTRACT

OBJECTIVE:To study the improving effects of argatroban on the brain damage of model rats with cerebral hemor-rhage. METHODS:50 SD rats were randomly divided into normal control group(equivalent normal saline),model group(equiva-lent normal saline),argatroban high,medium and low dose groups (0.75,1.5,3 mg/kg). All groups,except for normal control group,were reproduced models with cerebral hemorrhage,and the rats in each group were treated by corresponding drugs after 30 min,ip,once a day. The rats were executed after continuous administration for 3 days. The data was detected,including the con-tents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),activity of cysteine-containing aspartic protease 3(Caspase-3), expressions of Bcl-2,Bax,matrix metalloproteinase-2(MMP-2)and MMP-9,and the phosphorylations of nuclear factor κB(NF-κB) p65 and IκBα. RESULTS:Compared with the normal control group,the contents of TNF-α and IL-1β,the activity of Cas-pase-3,the expressions of MMP-2,MMP-9 and Bax proteins were increased;the expression of Bcl-2 was decreased;and phos-phorylations of NF- κB p65 and IκBα in model group were increased,with significant differences(P<0.01). Compared with the model group,the contents of TNF-α and IL-1β,the activity of Caspase-3,the expressions of MMP-2,MMP-9 and Bax were de-creased;the expression of Bcl-2 was increased;and phosphorylations of NF-κB p65 and IκBα in argatroban low,medium and high dose groups were decreased,with significant differences (P<0.01 or P<0.05). And it was positively correlated with the dose. CONCLUSIONS:Argatroban has dose-dependent inhibition effects on the inflammatory cytokine secretion and apoptosis of brain tissue of model rats with brain hemorrhage,and the mechanism may be related to NF-κB signaling pathway.