载ANM33双靶标超声脂质微泡在大鼠体内的药动力学特征研究  

Pharmacokinetic characteristics of ANM33-loaded dual-targeted ultrasound lipid microbubbles in rats

作　　者：麦丽和拜·阿斯海提 陈尚珂 穆玉明[1,2] MAILIHEBAI·Asihati;CHEN Shangke;MU Yuming(Department of Echocardiography,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China;Xinjiang Key Laboratory of Ultrasound Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第一附属医院心脏超声诊断科,新疆维吾尔自治区乌鲁木齐830000 [2]新疆超声医学重点实验室,新疆维吾尔自治区乌鲁木齐830000

出　　处：《临床超声医学杂志》2025年第3期177-182,共6页Journal of Clinical Ultrasound in Medicine

基　　金：国家自然科学基金项目(82060321);中央引导地方科技发展专项基金项目(ZYYD2023A02);新疆维吾尔自治区自然科学基金项目(2022D01C491);新疆医科大学第一附属医院卓越人才与创新团队培养项目(cxtd202424)。

摘　　要：目的 探讨载反义核苷酸(ANM33)双靶标超声脂质微泡在大鼠体内的药动力学特征。方法 使用超声造影评价琼脂糖凝胶仿体中载ANM33双靶标超声脂质微泡浓度分别为1×10^(4)/ml、1×10^(5)/ml、1×10^(6)/ml、1×10^(7)/ml、1×10^(8)/ml时的体外显影效果。然后使用紫外光谱分析法确定ANM33溶液的最大吸收波长,分析ANM33标准血浆溶液在0.1~10.0μg/ml浓度范围的线性关系,建立回归方程;分别使用精密度试验和回收率试验获取不同浓度(0.3、2.5、9.0μg/ml)ANM33标准血浆样品的日间、日内精密度相对标准偏差(RSD)及空白加标回收率;使用样品稳定性试验分析浓度为2.5μg/ml的ANM33标准血浆样品在25℃室温下放置4 h和-20℃低温下放置5 d的稳定性。将20只SD雄性大鼠随机分为2组,每组各10只,分别经尾静脉注射1.5 ml载ANM33双靶标微泡造影剂和PBS(空白对照),计算ANM33在大鼠体内主要药动力学参数,包括消除半衰期(t1/2)、最大血药浓度(C_(max))、清除率(CL)、转运速率(K_(21)、K_(12))、_(0~6) h药物浓度-时间曲线下面积(AUC_(0~6))、0 h到无穷大药物浓度-时间曲线下面积(AUC_(0~∞))。结果 超声造影检查结果显示,除浓度为1×10^(5)/ml与1×10^(6)/ml、1×10^(7)/ml与1×10^(8)/ml载ANM33双靶标超声脂质微泡的体外显影强度比较差异均无统计学意义外,其余浓度载ANM33双靶标超声脂质微泡的体外显影强度两两比较差异均有统计学意义(均P<0.05)。紫外光谱分析法显示,在室温条件下ANM33溶液的最大吸收波长为550 nm,故选取550 nm进行后续实验。ANM33标准血浆溶液在0.1~10.0μg/ml浓度范围线性关系良好,线性回归方程为:Y=0.193X+0.024(r=0.9992,P<0.001)。浓度为0.3、2.5、9.0μg/ml的ANM33标准血浆样品的日内精密度RSD分别为7.40%、5.85%、4.38%,日间精密度RSD分别为7.14%、4.93%、3.96%,空白加标回收率为91%~110%。浓度为2.5μg/ml的ANM33标准血浆样品在25℃室温下放Objective To investigate the pharmacokinetic characteristics of ANM33-loaded dual-targeted ultrasound lipid microbubbles in rats.Methods The in vitro imaging effects of ANM33-loaded dual-targeted ultrasound lipid microbubbles at concentrations of 1×10^(4)/ml,1×10^(5)/ml,1×10^(6)/ml,1×10^(7)/ml,and 1×10^(8)/ml in agarose gel phantoms were evaluated by contrast-enhanced ultrasound.The maximum absorption wavelength of ANM33 solution was determined by ultraviolet(UV)spectroscopy,and the linear relationship of ANM33 standard plasma solutions within the concentration range of 0.1~10.0μg/ml was analyzed to establish a regression equation.Precision and recovery tests were used to obtain the relative standard deviation(RSD)of intra-day and inter-day precision and the recovery rate of blank spiked samples of ANM33 standard plasma solutions at different concentrations(0.3,2.5,9.0μg/ml).The stability of ANM33 standard plasma samples at a concentration of 2.5μg/ml was analyzed after being stored at 25℃for 4 h and at-20℃ for 5 d.20 male SD rats were randomly divided into two groups,10 rats in each group,and 1.5 ml of ANM33-loaded dual-targeted microbubbles contrast agent or PBS(blank control)was injected via the tail vein.The main pharmacokinetic parameters of ANM33 in rats were calculated,including elimination half-life(t1/2),maximum plasma concentration(C_(max)),clearance rate(CL),transfer rates(K_(21),K_(12)),area under the concentration-time curve from _(0~6) h(AUC_(0~6)),and area under the concentration-time curve from 0 h to infinity(AUC_(0~∞)).Results Contrast-enhanced ultrasound showed that,except for the comparisons between concentrations of 1×10^(5)/ml and 1×10^(6)/ml,1×10^(7)/ml and 1×10^(8)/ml,which showed no statistically significant differences in in vitro imaging intensity,all other pairwise comparisons showed statistically significant differences(all P<0.05).UV spectroscopy showed that the maximum absorption wavelength of ANM33 solution at room temperature was 550 nm,which was selected for sub

关 键 词：载ANM33双靶标超声脂质微泡 紫外光谱分析法 动脉粥样硬化 药动力学 大鼠 

分 类 号：R445.1[医药卫生—影像医学与核医学]