effect of Pravastatin on carotid artery thrombosis in rats under the stimulus of C reactive protein

CHU Luo-xiang; QIN Yue-qiu; ZHOU Su-xian; YANG Fan; LIANG Zhi-shan; MO Chang-gan

Abstract：Objective To investigate the effect of Pravastatin on carotid artery thrombosis in rats under the stimu-lus of C reactive protein (CRP).Methods Thirty-two Sprague -Dawley rats were divided into four groups , normal control group (normal diet and placebo);pravastatin group (fed with normal diet plus pravastatin (5 mg/kg· d) inter-vention);CRP group (fed with normal diet and were also given CRP (3 mg/kg) intravenously four hours prior to the in-duction of thrombus );pravastatin+CRP group ( Based on the normal diet feed plus pravastatin and CRP intervention ) . An occlusive thrombus was created in the carotid artery by application of Whatman paper soaked in 20%FeCl3.The time when occlusive thrombus formatted and weight of thrombus were recorded .The expression of platelet P -selectin was de-tected by flow cytometry with or without stimulus of PAR -4 agonist in vitro.The levels of soluble P and prothrombin frag-ments were detected by ELISA .Results The time when occlusive thrombus formatted was not altered by intravenous of CRP in the rats fed with or without Pravastatin .However , the duration of thrombosis was significantly increased in the group given Pravastatin (17.5 ±1.5 minutes vs.13 ±1.41 minutes, P<0.01).There was no significant difference in the weight of the thrombosis among all groups .The expression of P-selectin on platelets was low in all groups without sig-nificant difference among them , but it was significantly increased by PAR -4 agonist AYPGKF-NH2 (100 μmol/L) in vitro, as the positive percentage of P -selectin was increased to 46%from 3.4%at baseline .The P-selectin expression on platelets stimulated by AYPGKF-NH2 was reduced by either Pravastatin or CRP intervention , as P-selectin was re-duced by about 25%in the combination of Pravastatin and CRP .Serum soluble P-selectin was enhanced by about 22%by CRP, which was significantly inhibited by Pravastatin (9.64 ±0.81 vs.11.34 ±0.74 pg/mL, P<0.05).Serum F1+2 level was significantly increased 4 hours after intravenous CRP intervention (2.57 ±0.4 pg/mL vs.0.72 ±0.11 pg/mL, P<0.01), while pretreatment with Pravastatin could significantly reduce serum levels of F 1+2 (1.93 ±0.25 pg/mL) stimulated by CRP .Conclusion This study shows that Pravastatin delays thrombus formation in rat carotid arterial exposed to oxidant stress under the stimulus of CRP .The antithrombotic effect of statins in inflammatory state may bring more clinical benefits .