Background: An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid\r\nimpacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and\r\nlipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by\r\nsingle or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats.\r\nMethods: Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13),\r\nezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily,\r\npitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each\r\ngroup respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were\r\ndetermined by ELISA and lipid profile were measured by enzymatic assay.\r\nResults: Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin\r\nplus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p < 0.05 compared with\r\nplacebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy.\r\nEzetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or\r\nco-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with\r\nregard to lipid profile levels at day 3 (P > 0.05).\r\nConclusions: Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was\r\nfound prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly\r\nattenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination\r\nmay be better than the latter in future clinical application.
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