海藻/昆布粗多糖的经口亚急性毒性及影响肝药酶特性的研究

本研究从海藻/昆布药对临床应用的角度出发,以海藻/昆布药对的粗多糖组分为研究对象,探讨了药对粗多糖对大鼠的经口亚急性毒性以及对肝药酶活性的影响。通过试验设计,以雌雄各半SD大鼠连续经口给药2周不同剂量的药对粗多糖,记录给药期间大鼠生理状态和行为变化,末次给药后收集心、肝、脾、肺、肾等脏器做HE染色切片,光镜下观察组织病理学变化,并以探针底物体外温孵法测定给药后大鼠肝药酶活性变化。结果发现,给药后低剂量处理组10.8 g/(kg·d)]和高剂量处理组86.4 g/(kg·d)]大鼠的生理体征及脏器系数未见显著异常。在显微结构下,低剂量组各脏器形态基本正常,而高剂量组肝组织出现水肿、脂肪变及肝窦扩张,肺脏组织出现间质性炎症及气肿。低剂量组大鼠肝药酶活性未见异常,高剂量组肝药酶CYP3A4活性被显著诱导。由此推测,海藻/昆布粗多糖具有潜在细胞毒性,大剂量下可致肝、肺组织毒性损伤,并可能通过诱导肝药酶CYP3A4发生药物与药物的相互作用,最终影响药物的药效或产生不良反应等。

The subacute toxicity and influence on cytochrome P450 of Sargassum & Laminaria thallus by oral administration

This study aimed to tackle the problems about the subacute toxicity and influence on cytochromeP450(CYP) of Chinese medicine pair(CMP) of Sargassum&Laminaria thallus.Through the test design,18 SD rats,half male and half female,were randomly divided into three groups:low dose,high dose and control.All groups were treated with crude polysaccharides(extracted from Sargassum&Laminaria thallus)or saline by gavage for 2 weeks. During the dosing period,the physiological characteristics of all group members were observed regularly.Until last administration, the animals were sacrificed by anesthesia and were autopsied with the use of HE staining. Three specific probe drugs were utilized for co-incubating in rat liver microsomes to verify the activity of cytochromeP450 in liver.As the results showed,severe chronic pulmonary inflammatories were found in high dose group86.4 g/(kg·d)]and some adaptive changes occurred in the rat liver as well(e.g.cellular swelling&dilation of hepatic sinusoid)from HE staining. On the other hand,there were no significant changes on liver microsome CYP450 under low dose10.8 g/(kg·d)] while the high dose one had a significant inducing effect on CYP3A4.As for clinic application, the drug-drug interactions as well as hepatic and pulmonary toxicity might occur when the Chinese medicine pair of Sargassum&Laminaria thallus was taken in high dose orally.