| 摘要: |
| 【目的】建立小鼠组织中五味子甲素的质量浓度测定方法，并研究五味子甲素在小鼠体内的组织分布及其靶向治疗效果。【方法】将五味子甲素按25 mg/kg一次灌胃ICR雄性小鼠，于给药后0.5，1，2，3和4 h分别取小鼠心、肝、肾、脑，用生理盐水洗净后制成0.25 g/mL组织匀浆，以睾丸酮为内标物，采用高效液相色谱法（HPLC）测定五味子甲素在小鼠心、肝、肾、脑中的质量浓度，并对HPLC方法的专属性、回收率、精密度和稳定性进行考察。依据五味子甲素在各组织中的峰值及各时间段的质量浓度，确定其分布最高的组织，对质量浓度分布最高的组织进行相关的药理学评价。【结果】小鼠心、肝、肾、脑组织中五味子甲素质量浓度为0.625～20 μg/mL时，其质量浓度与五味子甲素/内标峰面积线性关系良好（r≥0.999 0）。HPLC法的专属性良好；日内精密度为(3.15±0.82)%～(4.77±0.57)%，日间精密度为(5.51±1.82)%～(8.46±2.93)%；稳定性试验的RSD<10%；绝对回收率为(89.04±3.82)%～(91.37±3.77)%，相对回收率为(95.65±5.76)%～(106.07±8.29)%。五味子甲素1次灌胃给药（剂量25 mg/kg）后在小鼠体内心、肝、肾、脑组织中均有分布，给药1 h后五味子甲素在小鼠心脏、脑组织中质量浓度达到峰值，给药2 h后在小鼠肝脏和肾脏中质量浓度达到峰值。整个分布情况显示，给药后1，2，3 h五味子甲素在小鼠肝脏组织中的质量浓度均高于其他组织，且达峰值时其质量浓度也显著高于心脏、肾脏、脑(P<0.05)；其次是肾脏，五味子甲素质量浓度较低的为心脏和脑。五味子甲素对CCl4所致的小鼠急性肝损伤确有一定的保护作用。【结论】该测定方法简便、快速、稳定，可用于小鼠内脏组织中五味子甲素质量浓度的测定；小鼠灌胃给药后五味子甲素在小鼠体内心、肝、肾、脑组织中均有分布，且达峰值时以肝脏中质量浓度最高，其次是肾脏，心脏与脑中较低；五味子甲素对CCl4所致的小鼠急性肝损伤有一定保护作用。 |
| 关键词: 五味子甲素 小鼠组织 靶向疗效 |
| DOI： |
| 分类号: |
| 基金项目:吉林省科技发展计划项目（20130206036YY）；吉林省发改委科研平台资助项目(2013G020) |
|
| Distribution characteristics of Schisandrin A in mice tissues and its targeting therapeutic effect |
|
ZHAO Zhenyu,JIANG Xiaohui,WANG Chunmei,et al
|
| Abstract: |
| 【Objective】This study established a method to detect the concentration of Schisandrin A in mice,investigated its distribution characteristics and examined its targeting therapeutic effect. 【Method】Schisandrin A at concentration of 25 mg/kg was administered orally to ICR mice and the concentrations in heart,brain,kidney and liver were measured using HPLC with testosterone as internal standard 0.5,1,2,3,and 4 h after administration.The specificity,recovery,accuracy and stability of HPLC method were also studied.The tissue with highest Schisandrin A contribution was determined and the biological activities were evaluated.【Result】The concentrations of Schisandrin A distribution in mice heart,liver,kidney,and brain tissues were 0.625 to 20 μg/mL,having a good linear relationship with the internal standard peak area ratio (r≥0.999 0).HPLC had a good specificity,with within day precision of (3.15±0.82)%-(4.77±0.57)% and between-day precision of (5.51±1.82)%-(8.46±2.93)%.The RSD of stability test was <10%,the absolute recovery was (89.04±3.82)%-(91.37±3.77)%,and the relative recovery was (95.65±5.76)%-(106.07±8.29)%.Schisandrin A was distributed in heart,liver,kidney and brain,and the times needed to reach peak concentration were 1 hour in heart and brain,and 2 hours in liver,and 3 hours in kidney.The concentration of Schisandrin A in liver was significantly higher than in kidney,heart and brain (P<0.05).Schisandrin A had protective effect on CCl4 induced acute liver injury in mice.【Conclusion】The established method was simple,rapid,stable,and can be used for determination of Schisandrin A in internal tissues of mice.After oral administration,peak and every time concentrations of Schisandrin A were highest in liver,and it can protect acute liver injury. |
| Key words: Schisandrin A mice tissue distribution targeting therapeutic effect |
