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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。
In this study, from the point of view of clinical application of seaweed / kelp medicine, the crude polysaccharides components of seaweed / kelp were used as the research object to investigate the oral subacute toxicity of crude polysaccharides to rats and the activity of hepatic drug Impact. Through experimental design, the male and female SD rats were orally administered with different dosages of crude polysaccharides continuously for 2 weeks. The physiological status and behavior of the rats during the administration were recorded. Heart, liver, spleen and lungs were collected after the last administration , Kidney and other organs were stained with HE, histopathological changes were observed under light microscope, and the change of enzyme activity in rat liver after administration was detected by probe substrate incubation in vitro. The results showed that there was no significant difference in the physical signs and organ coefficients between the low-dose group [10.8 g / (kg · d)] and the high-dose group [86.4 g / (kg · d)] after administration. Under the microstructure, the morphology of the organs in the low-dose group was basically normal, while the edema, steatosis and hepatic sinusoid expansion in the liver tissue of the high-dose group appeared, interstitial inflammation and emphysema in the lung tissue. The liver enzyme activity of rats in low dose group showed no abnormality, and the activity of hepatic drug CYP3A4 in high dose group was significantly induced. It is speculated that seaweed / laminaria crude polysaccharides have potential cytotoxicity, high doses can cause liver and lung toxicity, and may induce liver drug CYP3A4 drug and drug interactions occur, and ultimately affect the drug’s efficacy or produce Adverse reactions.