灯盏乙素对大鼠瑞舒伐他汀血浆浓度及组织分布的影响
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摘要
目的考察大鼠体内灯盏乙素对瑞舒伐他汀血浆浓度和组织分布的影响。方法按照体重将大鼠随机分成4组,每组18只:对照组、实验Ⅰ组、实验Ⅱ组和实验Ⅲ组。实验Ⅰ组、实验Ⅱ组和实验Ⅲ组分别灌胃10,50,200 mg·kg-1灯盏乙素,同时均灌胃瑞舒伐他汀5 mg·kg~(-1);对照组灌胃等体积0.2%CMC-Na水溶液。分别于给药后1,2,6 h摘眼球取血,取血后立即处死大鼠,取出心、肝、肺、肾、脑组织处理,HPLC-MS测定血浆及组织的瑞舒伐他汀含量。结果所建立的瑞舒伐他汀血浆及组织样本HPLC-MS法符合要求。对照组、实验Ⅰ组、实验Ⅱ组和实验Ⅲ组大鼠的血浆瑞舒伐他汀浓度在1 h分别为(170.38±40.77),(218.09±59.52),(278.64±76.26),(297.48±95.37)ng·m L~(-1);在2 h分别为(237.26±70.31),(293.76±89.04),(410.27±102.13),(461.49±121.73)ng·m L~(-1);在6 h分别为(131.58±40.52),(166.21±48.52),(236.78±73.40)和(251.33±82.94)ng·m L~(-1),各实验组大鼠瑞舒伐他汀血浆浓度高于对照组,差异均有统计学意义(均P<0.05)。各组大鼠的瑞舒伐他汀均主要聚集于肝,对照组、实验Ⅰ组、实验Ⅱ组和实验Ⅲ组在大鼠肝的瑞舒伐他汀浓度在1 h分别为(2098.57±735.10),(1905.91±703.16),(1406.39±435.86),(1217.08±318.65)ng·m L~(-1);这4组在2 h分别为(3204.19±893.53),(2863.87±836.12),(2114.28±598.31),(1973.15±512.64)ng·m L~(-1);这4组在6 h分别为(1681.71±513.29),(1603.14±517.86),(1120.08±298.75),(1057.91±267.66)ng·m L~(-1),实验Ⅱ组和实验Ⅲ组在肝的瑞舒伐他汀浓度低于对照组;实验组Ⅲ组的瑞舒伐他汀在大鼠的心、肺、肾及脑组织的浓度高于对照组,以上差异均有统计学意义(均P<0.05)。结论剂量达到50 mg·kg-1的灯盏乙素对瑞舒伐他汀血浆浓度及肝组织分布均有显著影响,其分布机制可能与竞争蛋白转运体有关。
Objective To study the influence of scutellarin on the plasma concentration and tissue distributions of rosuvastatin in rats. Methods Male sprague-dawley rats were randomly divided into four groups:control group,experimental Ⅰ group,experimental Ⅱ group and experimental Ⅲ group. All rats were orally administrated with rosuvastatin( 5 mg·kg~(-1)). In low, medium, largethree doses( 10,50,150 mg·kg-1 scutellarin) of experimental groups,scutellarin were added,respectively. Plasma samples were collected by picking eyeballs 1,2,6 hafter administration. Then the rats were sacrificed and heart,liver,kidney,lung and brain were collected. The concentration of rosuvastatin in plasma and tissues were detected by HPLC-MS. Results The established HPLC-MS analyse method is in line with the requirements of this study. Concentrations of rosuvastatin in plasma at different time points were as follows: at 1 h it were( 170. 38 ± 40. 77),( 218. 09 ± 59. 52),( 278. 64 ± 76. 26),( 297. 48 ± 95. 37)ng·m L~(-1); at 2 h it were( 237. 26 ± 70. 31),( 293. 76 ± 89. 04),( 410. 27 ± 102. 13),( 461. 49 ± 121. 73)ng·m L~(-1); at 6 h it were( 131. 58 ± 40. 52),( 166. 21 ± 48. 52),( 236. 78 ± 73. 40),( 251. 33 ± 82. 94) ng·m L~(-1).The concentration of rosuvastatin in experimental of rats plasma is higher than that of control group with significantly( all P < 0. 05). The rosuvastatin is mainly accumulated in the liver of the rats. Concentrations of rosuvastatin in liver at different time points were as follows: at 1 h it were( 2098. 57 ± 735. 10),( 1905. 91 ± 703. 16),( 1406. 39 ± 435. 86),( 1217. 08 ±318. 65) ng·m L~(-1); at 2 h it were( 3204. 19 ± 893. 53),( 2863. 87 ± 836. 12),( 2114. 28 ± 598. 31),( 1973. 15 ± 512. 64) ng·m L~(-1); at 6 h it were( 1681. 71 ± 513. 29),( 1603. 14 ± 517. 86),( 1120. 08 ± 298. 75),( 1057. 91 ± 267. 66) ng·m L~(-1). In liver tissue,the concentration of rosuvastatin in experimental group Ⅱ and Ⅲ were lower than that of the control group with significantly( all P < 0. 05). The concentration of rosuvastatin in heart,lung and kidney and brain tissue increased in experimental Ⅲ group; compared to that of the control group,the difference had significant difference( all P < 0. 05). Conclusion A specific concentration range of scutellarin can affect the plasma concentration and tissue distributions of rosuvastatin while rats were administrated with 5 mg·kg-1 of rosuvastatin.The concentration of rosuvastatin in liver under combined administration model was decreased,especially. This may be related to the competitive protein transporter.
Objective To study the influence of scutellarin on the plasma concentration and tissue distributions of rosuvastatin in rats. Methods Male sprague-dawley rats were randomly divided into four groups:control group,experimental Ⅰ group,experimental Ⅱ group and experimental Ⅲ group. All rats were orally administrated with rosuvastatin( 5 mg·kg~(-1)). In low, medium, largethree doses( 10,50,150 mg·kg-1 scutellarin) of experimental groups,scutellarin were added,respectively. Plasma samples were collected by picking eyeballs 1,2,6 hafter administration. Then the rats were sacrificed and heart,liver,kidney,lung and brain were collected. The concentration of rosuvastatin in plasma and tissues were detected by HPLC-MS. Results The established HPLC-MS analyse method is in line with the requirements of this study. Concentrations of rosuvastatin in plasma at different time points were as follows: at 1 h it were( 170. 38 ± 40. 77),( 218. 09 ± 59. 52),( 278. 64 ± 76. 26),( 297. 48 ± 95. 37)ng·m L~(-1); at 2 h it were( 237. 26 ± 70. 31),( 293. 76 ± 89. 04),( 410. 27 ± 102. 13),( 461. 49 ± 121. 73)ng·m L~(-1); at 6 h it were( 131. 58 ± 40. 52),( 166. 21 ± 48. 52),( 236. 78 ± 73. 40),( 251. 33 ± 82. 94) ng·m L~(-1).The concentration of rosuvastatin in experimental of rats plasma is higher than that of control group with significantly( all P < 0. 05). The rosuvastatin is mainly accumulated in the liver of the rats. Concentrations of rosuvastatin in liver at different time points were as follows: at 1 h it were( 2098. 57 ± 735. 10),( 1905. 91 ± 703. 16),( 1406. 39 ± 435. 86),( 1217. 08 ±318. 65) ng·m L~(-1); at 2 h it were( 3204. 19 ± 893. 53),( 2863. 87 ± 836. 12),( 2114. 28 ± 598. 31),( 1973. 15 ± 512. 64) ng·m L~(-1); at 6 h it were( 1681. 71 ± 513. 29),( 1603. 14 ± 517. 86),( 1120. 08 ± 298. 75),( 1057. 91 ± 267. 66) ng·m L~(-1). In liver tissue,the concentration of rosuvastatin in experimental group Ⅱ and Ⅲ were lower than that of the control group with significantly( all P < 0. 05). The concentration of rosuvastatin in heart,lung and kidney and brain tissue increased in experimental Ⅲ group; compared to that of the control group,the difference had significant difference( all P < 0. 05). Conclusion A specific concentration range of scutellarin can affect the plasma concentration and tissue distributions of rosuvastatin while rats were administrated with 5 mg·kg-1 of rosuvastatin.The concentration of rosuvastatin in liver under combined administration model was decreased,especially. This may be related to the competitive protein transporter.
引文
[1]石美娜,杨为民,刘璇.灯盏花乙素药理作用研究进展[J].昆明医科大学学报,2013,9(9):80-83.
[2]辛传伟,石佳娜,黄萍.灯盏细辛注射液门诊处方合理性分析[J].中国临床药理学杂志,2012,28(7):541-542.
[3]NEZASA K,TAKAO A,KIMURA K,et a1.Pharmacokinetics and disposition of rosuvastatin,a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,in rat[J].Xenobiotica,2002,32(8):715-727.
[4]刘建明,叶锡勇,刘志军,等.灯盏乙素对瑞舒伐他汀在大鼠体内药代动力学的影响[J].中国临床药理学杂志,2017,33(11):33-36.
[5]邓鸣,刘会臣.普伐他汀在大鼠小肠中的吸收和肝中的分布[J].中国药学杂志,2005,41(22):1733-1737.
[6]温金华,袁钊,熊玉卿.瑞舒伐他汀药代动力学及与其他药物的相互作用研究进展[J].中国临床药理学与治疗学,2011,16(11):1309-1314.
[7]张伟,贺毅憬,周宏灏.有机阴离子转运多肽1B1的遗传药理学进展[J].中国临床药理学与治疗学,2008,13(7):721-729.
[8]邓晟,李元建.HMG-Co A还原酶抑制药与转运体OATP1B1[J].中南药学,2008,6(5):583-586.
[2]辛传伟,石佳娜,黄萍.灯盏细辛注射液门诊处方合理性分析[J].中国临床药理学杂志,2012,28(7):541-542.
[3]NEZASA K,TAKAO A,KIMURA K,et a1.Pharmacokinetics and disposition of rosuvastatin,a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,in rat[J].Xenobiotica,2002,32(8):715-727.
[4]刘建明,叶锡勇,刘志军,等.灯盏乙素对瑞舒伐他汀在大鼠体内药代动力学的影响[J].中国临床药理学杂志,2017,33(11):33-36.
[5]邓鸣,刘会臣.普伐他汀在大鼠小肠中的吸收和肝中的分布[J].中国药学杂志,2005,41(22):1733-1737.
[6]温金华,袁钊,熊玉卿.瑞舒伐他汀药代动力学及与其他药物的相互作用研究进展[J].中国临床药理学与治疗学,2011,16(11):1309-1314.
[7]张伟,贺毅憬,周宏灏.有机阴离子转运多肽1B1的遗传药理学进展[J].中国临床药理学与治疗学,2008,13(7):721-729.
[8]邓晟,李元建.HMG-Co A还原酶抑制药与转运体OATP1B1[J].中南药学,2008,6(5):583-586.