脱氢乙酸钠通过抑制肝脏中VKORC1影响大鼠的凝血功能

Sodium Dehydroacetate Affects the Coagulation Function of Rats by Inhibiting VKORC1 in the Liver

为研究脱氢乙酸钠(sodium dehydroacetate,DHA-S)对大鼠凝血功能及肝脏中Vkorc1的影响,用200 mg/kg的脱氢乙酸钠处理不同性别大鼠后,分别测定凝血酶原时间(PT)和部分活化凝血酶原时间(APTT);HPLC法检测大鼠肝脏中DHA-S的含量,Western blot及RT-qPCR方法检测肝脏中Vkorc1的表达水平。结果显示,给予DHA-S后,雄、雌鼠的PT值分别为对照组的1.18~1.48倍和1.28~2.01倍,APTT值分别为对照组的1.15~1.37倍和1.21~1.71倍,雌、雄鼠间存在显著差异(P<0.05);DHA-S处理3~9 d后,雌性大鼠肝脏中的DHA-S水平是雄性大鼠的1.9~3.2倍;DHA-S处理组大鼠肝脏中Vkorc1的蛋白表达及其mRNA水平显著降低(P<0.05),且雌鼠肝脏的Vkorc1 mRNA显著低于雄鼠。表明DHA-S可引起大鼠凝血异常,雌雄大鼠对DHA-S的敏感性不同与DHA-S在肝脏中的浓度及对肝脏中VKORC1的抑制有关。

In order to study the effect of sodium dehydroacetate(DHA-S)on coagulation function and Vkorc1 in liver of rats,the prothrombin time(PT)and partially activated prothrombin time(APTT)of rats of different sexes were measured after treatment with 200 mg/kg of sodium dehydroacetate;The content of DHA-S in rat liver was detected by HPLC,and the expression of Vkorc1 in liver was detected by Western blot and RT-qPCR.The results showed that the PT values of male and female rats after DHA-S administration were 1.18-1.48 times and 1.28-2.01 times of the control group respectively,and the APTT values were 1.15-1.37 times and 1.21-1.71 times of the control group respectively.There was significant difference between male and female rats;After 3-9 days of treatment with DHA-S,the level of DHA-S in the liver of female rats was 1.9-3.2 times higher than that of male rats;The protein expression and mRNA level of Vkorc1 in the liver of DHA-S treated rats decreased significantly(P<0.05).It is concluded that DHA-S can cause abnormal blood coagulation in rats.The different sensitivity of male and female rats to DHA-S is related to the concentration of DHA-S in the liver and the inhibition of Vkorc1 in the liver.