[關(guān)鍵詞]
[摘要]
目的 探討?zhàn)B陰通腦顆粒主要有效部位（總生物堿、總黃酮、總皂苷、總酚酸）配伍后在腦缺血再灌注模型大鼠體內(nèi)藥物濃度及其藥動(dòng)學(xué)與藥效學(xué)變化。方法 采用正交試驗(yàn)法組成上述主要有效部位用量配比不同的9個(gè)組方，供腦缺血再灌注模型大鼠ig給藥，高效液相色譜-二極管陣列檢測(cè)器（HPLC-DAD）測(cè)定不同時(shí)間點(diǎn)血漿中的葛根素、阿魏酸和川芎嗪血漿藥物濃度。DAS3.2.6軟件以非房室模型擬合藥動(dòng)學(xué)參數(shù)，并運(yùn)用總量統(tǒng)計(jì)矩法和綜合評(píng)分法對(duì)整體藥動(dòng)學(xué)特征進(jìn)行評(píng)價(jià)。同時(shí)采用酶聯(lián)免疫吸附測(cè)定（ELISA）法測(cè)定大鼠血漿中超氧化物歧化酶（SOD）和過(guò)氧化氫酶（CAT）的含量。最后進(jìn)行藥動(dòng)學(xué)-藥效學(xué)（PK-PD）模型研究，獲得各藥物濃度與藥效之間的定量方程。結(jié)果 葛根素、阿魏酸和川芎嗪在模型大鼠體內(nèi)的藥動(dòng)學(xué)特征有所差異?？偭拷y(tǒng)計(jì)矩和綜合評(píng)分研究表明不同配伍對(duì)總量零階矩、總量平均滯留時(shí)間、綜合評(píng)分等參數(shù)影響不一。主要有效部位正交配伍給藥后，一定程度上會(huì)抑制腦缺血再灌注大鼠血漿中SOD和CAT的降低。各PK-PD模型均采用Sigmoid-Emax模型，擬合結(jié)果與實(shí)測(cè)數(shù)據(jù)之間相關(guān)性良好，R值均大于0.85。結(jié)論 養(yǎng)陰通腦顆粒主要有效部位配伍對(duì)模型大鼠體內(nèi)的藥動(dòng)學(xué)行為和抗氧化指標(biāo)具有一定影響；中藥復(fù)方多成分藥物代謝動(dòng)力學(xué)可采用總量統(tǒng)計(jì)矩和綜合評(píng)分法進(jìn)行研究；PK-PD結(jié)合模型可用于中藥復(fù)方多成分藥動(dòng)學(xué)與藥效學(xué)之間相關(guān)性的評(píng)價(jià)與預(yù)測(cè)。
[Key word]
[Abstract]
Objective To investigate the pharmacokinetic and pharmacodynamic changes of Yangyin Tongnao Granules (YTG) in cerebral ischemia reperfusion rats after the compatibility of main effective parts (total alkaloids, total flavonoids, total saponins and total phenolic acids). Methods By using the orthogonal design to research the main effective parts of YTG, nine different dosage ratios combinations were formed, which were used for oral administration in cerebral ischemia reperfusion rats. High performance liquid chromatography-diode array detector (HPLC-DAD) was used to determine the concentration of puerarin, ferulic acid, and ligustrazine in rat plasma at different time points. The non-compartmental model was used to fit the pharmacokinetic parameters by Drug and Statistics (DAS) 3.2.6 software. The total quantum statistical moment analysis method and comprehensive evaluation method were used to evaluate the total pharmacokinetic characteristics. Meanwhile, the content of superoxide dismutase (SOD) and catalase (CAT) were determined by enzyme-linked immunosorbent assay (ELISA) kits. Finally, the PK-PD model and the quantitative equations between drug concentration and efficacy were obtained. Results The pharmacokinetic characteristics of puerarin, ferulic acid and ligustrazine in cerebral ischemia-reperfusion rats were different. Total statistical moment and comprehensive score study showed that different combinations had different effects on ACUT, mean retention time (MRT), and comprehensive evaluation. The effective parts inhibited the reduction of oxidation indexes such as SOD and CAT. Sigmoid-Emax models were adopted in all PK-PD models, and the fitting results had a good correlation with the measured data. The R values were more than 0.85. Conclusion Compatibility of YTG activity parts had a certain effect on their pharmacokinetic behaviors and antioxidation in model rats. The total quantum statistical moment analysis and comprehensive evaluation method can be used to study the pharmacokinetics of multi-component traditional Chinese medicine prescriptions. PK-PD model could be used to predict and evaluate the correlation between pharmacokinetics and pharmacodynamics of traditional Chinese medicine prescriptions.
[中圖分類(lèi)號(hào)]
[基金項(xiàng)目]
國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目（81630105）；國(guó)家重點(diǎn)研發(fā)計(jì)劃中醫(yī)藥現(xiàn)代化研究重點(diǎn)專(zhuān)項(xiàng)（2017YFC1700400）；國(guó)家重點(diǎn)研發(fā)計(jì)劃中醫(yī)藥現(xiàn)代化研究重點(diǎn)專(zhuān)項(xiàng)（2017YFC1700403）；國(guó)家自然科學(xué)基金青年項(xiàng)目（81904083）；浙江省基礎(chǔ)公益研究計(jì)劃項(xiàng)目（LGN18A010001）；中國(guó)博士后科學(xué)基金面上資助項(xiàng)目（2018M630692）；浙江省中醫(yī)藥科技計(jì)劃項(xiàng)目（2017ZB024）
