博落回提取物对草鱼生长性能的影响及其效用成分的药代动力学和残留消除研究

doi:10.11843/j.issn.0366-6964.2025.08.039

摘要/Abstract

摘要：

本研究旨在观察博落回提取物(MCE)对草鱼的促生长作用以及表征其主要成分血根碱(SAN)和白屈菜红碱(CHE)在草鱼中的药代动力学特性和肌肉残留。选用450尾约10.5 g的草鱼，随机分为5组，分别饲喂含0、30、60和120 mg·kg^-1博落回散(MCEP)和盐酸甜菜碱的日粮，饲养60 d。选取120尾250 g左右的草鱼进行药代动力学研究，随机分为5组，分别静脉注射(0.0012、0.012和0.024 mg·kg^-1)和灌胃(0.06和0.6 mg·kg^-1)MCE，使用液相色谱串联三重四级杆质谱(LC-QQQ-MS)测定血液中SAN和CHE含量。选取150尾50 g左右的草鱼饲喂含MCEP的日粮(60 mg·kg^-1饲料)60 d，使用LC-QQQ-MS测定草鱼带皮肌肉中SAN和CHE含量。结果表明：MCE可以显著提高草鱼的生长性能和肥满度(P < 0.05)；灌胃0.6 mg·kg^-1 MCE后，SAN和CHE主要的药代动力学(PK)参数分别为C_max=(19.157±1.924)和(6.388±1.356) μg·L^-1，AUC_(0-t)=(3.317±0.274) 和(0.651±0.114)(μg·L^-1)·h，T_1/2=(9.065±2.286) h(CHE无有效数据)。静脉注射0.024 mg·kg^-1 MCE，5 min后SAN和CHE的AUC_(0-t)分别为(37.132±4.124)和(0.614±0.039)(μg·L^-1)·h，AUC_(0-∞)分别为(60.583±7.512)和(0.750±0.055)(μg·L^-1)·h；残留试验中，肌肉中SAN和CHE在停药后第5天降至定量限下。饲料中添加60 mg·kg^-1 MCEP能够显著提高草鱼的生长性能；SAN和CHE均表现出吸收快，分布广和消除迅速的PK性质，但在高剂量下使用，两种活性物质会表现出明显的非线性PK特征；临床使用MCE后停药5 d，肌肉中SAN和CHE基本完全消除。这项研究对MCE的合理用药，开发以及相关的风险评估具有重要意义。

关键词: 博落回提取物, 草鱼, 生长性能, 血根碱, 白屈菜红碱, 药代动力学, 残留消除

Abstract:

The objective of this study was to observe the growth-promoting effect of Macleaya cordata extract (MCE) on grass carp (Ctenopharyngodon idellus) and to characterize the pharmacokinetic properties and muscle residues of its main active components, sanguinarine (SAN) and chelerythrine (CHE). Four hundred and fifty grass carp weighing 10.5 g were randomly divided into 5 groups and fed with diets containing 0, 30, 60 and 120 mg·kg^-1 MCE Pulvis (MCEP) and betaine hydrochloride respectively for 60 days. A total of 120 grass carp weighing 250 g were randomly divided into 5 groups. MCE was administered intravenously (0.001 2 mg·kg^-1, 0.012 mg·kg^-1, 0.024 mg·kg^-1) or gavage (0.06 mg·kg^-1, 0.6 mg·kg^-1). The concentrations of SAN and CHE in blood were determined by liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS). Another 150 grass carp of 50 g were fed with MCEP (60 mg·kg^-1 feed) for 60 days. SAN and CHE contents in skinned muscle of grass carp were determined by LC-QQQ-MS. The results showed that MCE could significantly improve growth performance and condition factor of grass carp (PP < 0.05); After oral administration of 0.6 mg·kg^-1 MCE, the main pharmacokinetic (PK) parameters of MCE, SAN and CHE administered orally at 0.6 mg·kg^-1 were C_max=19.157±1.924 and 6.388±1.356 μg·L^-1, AUC_(0-t)=3.317±0.274 and 0.651±0.114 (μg·L^-1)·h, T_1/2=9.065±2.286 h (CHE had no valid data), respectively. 5 min after intravenous injection of 0.0245 mg·kg^-1 MCE, AUC_(0-t) of SAN and CHE were 37.132±4.124 and 0.614±0.039 (μg·L^-1) ·h, AUC_(0-∞) were 60.583±7.512 and 0.750±0.055 (μg·L^-1)·h, respectively; In the residue assay, SAN and CHE in muscle decreased below the limit of quantification on day 5 after withdrawal. The results suggested that 60 mg·kg^-1 MCEP could significantly improve the growth performance of grass carp. SAN and CHE in plasma showed PK characteristics of fast absorption, wide distribution and rapid elimination. However, at high doses, the two active substances exhibit significant nonlinear PK profiles; SAN and CHE in muscle were almost completely eliminated after 5 days withdrawal of MCE. This study is of great significance in the rational use of MCE, its development and related risk assessment.

Key words: Macleaya cordata extract, grass carp, growth properties, sanguinarine, chelerythrine, pharmacokinetics, residue elimination

中图分类号:

张皓阳, 刘薇, 孙文清, 徐玉凤, 刘芷芹, 杨子辉, 董朕, 曾建国. 博落回提取物对草鱼生长性能的影响及其效用成分的药代动力学和残留消除研究[J]. 畜牧兽医学报, 2025, 56(8): 4018-4030.

ZHANG Haoyang, LIU WEI, SUN Wenqing, XU Yufeng, LIU Zhiqin, YANG Zihui, DONG Zhen, ZENG Jianguo. Effects of Macleaya Cordata Extract on Growth Performance of Grass Carp and Pharmacokinetics and Residue Elimination of Its Utility Components[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(8): 4018-4030.

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分析物 Analyte	保留时间/min Retention time	监测离子对(m/z) Monitoring ion pairs	碎裂电压/V Fragmentor voltage	碰撞能量/eV Collision energy
SAN	1.822	332.1→273.9^*，332.1→316.9	143	35
CHE	1.918	348.1→332.0^*，348.1→304.1	150	30
TET	1.756	356.0→192.0^*，356.0→165.0	142	26

组别 Groups	初始体重/g Initial body weight	终末体重/g Terminal body weight	相对增重率/% Relative weight gain rate	平均日增重/g Average daily gain	饵料系数 Feed coefficient
空白对照组 Blank control group	10.3±0.4^a	23.3±4.3^a	127.0±45.5^a	0.22±0.07^a	2.58±1.09^b
甜菜碱组 Betaine group	10.7±0.5^a	27.6±2.7^a	157.3±14.5^a	0.28±0.04^a	1.80±0.25^ab
30 mg·kg^-1 MCEP	10.4±0.6^a	24.1±3.2^a	131.1±16.8^a	0.23±0.04^a	2.25±0.39^ab
60 mg·kg^-1 MCEP	10.7±0.7^a	37.1±12.3^b	242.7±96.2^b	0.44±0.19^b	1.34±0.63^a
120 mg·kg^-1 MCEP	10.3±0.5^a	24.3±1.6^a	135.1±9.9^a	0.23±0.02^a	2.16±0.19^ab

组别 Groups	体长/cm Body length	体重/g Body weight	肝脏重/g Liver weight	肝体比 Hepatosomatic index	肥满度 Fulton′s condition index (K)
空白对照组 Blank control group	11.3±1.3	23.3±4.3	0.50±0.08	2.16±0.06^a	1.65±0.24^a
甜菜碱组 Betaine group	12.4±0.8	27.6±2.7	0.50±0.08	1.82±0.29^a	1.46±0.14^a
30 mg·kg^-1 MCEP	11.6±1.0	24.1±3.2	0.50±0.00	2.11±0.27^a	1.54±0.19^a
60 mg·kg^-1 MCEP	12.6±1.4	37.1±12.3	0.67±0.05	1.99±0.73^b	1.79±0.18^b
120 mg·kg^-1 MCEP	11.8±0.4	24.3±1.6	0.53±0.05	2.16±0.14^a	1.47±0.08^a

样品 Sample	分析物 Analyte	回归方程 Regression equation	相关系数 R²	线性范围 Linearity range
血浆 Plasma	SAN	y=0.002 104*x+0.007 727	0.999 8	0.5~200.0 μg·L^-1
血浆 Plasma	CHE	y=0.013 691*x+0.040 129	0.999 6	0.5~200.0 μg·L^-1
肌肉 Muscle	SAN	y=0.007 480*x+0.001 696	0.999 9	5.0~1 000.0 μg·kg^-1
肌肉 Muscle	CHE	y=0.059 915*x-0.014 136	0.999 9	5.0~1 000.0 μg·kg^-1

样品 Sample	分析物 Analyte	理论浓度/(μg·L^-1) Theoretical concentration	平均基质效应/% Mean matrix effect	基质效应RSD/% RSD of matrix effect
血浆 Plasma	SAN	0.500	100.493	1.407
		5.000	99.542	0.662
		50.000	99.047	0.750
	CHE	0.500	100.408	1.157
		5.000	96.982	0.752
		50.000	103.065	1.060
肌肉 Muscle	SAN	0.500	100.332	0.422
		5.000	99.635	0.272
		50.000	99.502	0.389
	CHE	0.500	100.376	0.651
		5.000	99.820	0.577
		50.000	100.242	0.675