摘要
目的:研究盐酸小檗碱对大鼠体内低剂量阿托伐他汀的药动学影响。方法:选取18只SD健康雄性大鼠进行研究,以随机双盲对照法将其分成A组、B组、C组,每组6只。其中A组予以10mg/kg的阿托伐他汀钙灌胃处理;B组予以小檗碱30mg/kg+阿托伐他汀钙10mg/kg相继灌胃;C组予以小檗碱90mg/kg+阿托伐他汀钙10mg/kg相继灌胃。检测并比较三组大鼠眼眶血中阿托伐他汀钙含量、血药浓度,绘制阿托伐他汀钙的药时曲线,计算药代动力学参数。此外,采集所有大鼠肝脏组织,检测细胞色素P450(CYP450)以及P-糖蛋白(P-gp)蛋白表达情况。比较各组大鼠肝脏组织UGT、GST及GSH含量。结果:B组、C组大鼠给药2h后血浆阿托伐他汀钙含量分别为(7.04±0.37)μg/ml、(7.88±0.43)μg/ml,均高于A组的(6.00±0.31)μg/ml,且C组大鼠给药2h后血浆阿托伐他汀钙含量高于B组(均P<0.05);三组大鼠给药前以及给药4h、6h、8h后的血浆阿托伐他汀钙含量对比均不明显(均P>0.05)。B组、C组大鼠t_(max)水平低于A组,且C组大鼠t_(max)水平低于B组;B组、C组大鼠C_(max)、t_(1/2)、CL以及MRT水平均高于A组,且C组大鼠C_(max)、t_(1/2)、CL以及MRT水平均高于B组(均P<0.05)。B组、C组肝脏CYP450以及P-gp表达均高于A组(均P<0.05);且B组和C组肝脏CYP450以及P-gp表达的差异无统计学意义(均P>0.05)。B组、C组大鼠肝组织UGT、GST活性均低于A组,且C组上述指标活性均低于B组;B组、C组大鼠肝组织GSH活性均高于A组,且C组GSH活性高于B组(均P<0.05)。结论:盐酸小檗碱对大鼠体内低剂量阿托伐他汀的药动学有一定影响,表现为血药浓度有升高趋势,需谨慎联用。
Objective:To study the effect of Berberine hydrochloride on the pharmacokinetics of low dose Atorvastatin in rats.Methods:18 healthy male SD rats were selected for the study and randomly divided into group A,group B,and group C using a double blind control method,with 6 rats in each group.In group A,10mg/kg Atorvastatin calcium was administered by gavage;group B was given Berberine 30mg/kg+Atorvastatin calcium 10mg/kg by gavage successively;group C was given Berberine 90mg/kg+Atorvastatin calcium 10mg/kg by gavage successively.The content of atorvastatin calcium in the orbital blood of the three groups of rats and the blood concentration were detected and compared,draw the drug time curve of Tacrolimus,and calculate the pharmacokinetic parameters.In addition,all rat liver tissues were collected to detect the expression of Cytochrome P450(CYP450)and P-glycoprotein(P-gp)protein.Compare the content of UGT,GST,and GSH in the liver tissue of rats in each group.Results:The plasma Atorvastatin calcium content of rats in group B and group C 2 hours after administration was(7.04±0.37)μg/ml,(7.88±0.43)μg/ml,all higher than group A’s(6.00±0.31)μg/ml,and the plasma Atorvastatin calcium content of rats in group C was higher than that in group B at 2 hours after administration(all P<0.05).The comparison of plasma Atorvastatin calcium content before administration and 4,6 and 8 hours after administration was not significant in the three groups(all P>0.05).The t_(max) levels in group B and group C rats were lower than those in group A,and the t_(max) levels in group C rats were lower than those in group B;the levels of C_(max),t_(1/2),CL,and MRT in group B and group C rats were higher than those in group A,and the levels of C_(max),t_(1/2),CL,and MRT in group C rats were higher than those in group B(all P<0.05).The expression of CYP450 and P-gp in the liver of group B and group C was higher than that of group A(both P<0.05).There was no statistically significant difference in the expression of CYP450 and P-gp in the live
作者
余瑞莲
张庆平
廖辉雄
梁啦迪
崔莉婉
YU Ruilian;ZHANG Qingping;LIAO Huixiong(Department of Pharmacy,People’s Hospital of Longhua District,Shenzhen City,Guangdong Province 518109)
出处
《医学理论与实践》
2024年第3期367-370,共4页
The Journal of Medical Theory and Practice
基金
深圳市龙华区医疗卫生机构区级科研项目(2020011)。
关键词
阿托伐他汀
盐酸小檗碱
大鼠
药动学
血药浓度
联合用药
Atorvastatin
Berberine hydrochloride
Rats
Pharmacokinetics
Blood drug concentration
Combined medication
