对乙酰氨基酚在家蚕体内的糖基化代谢特点和对组织的损伤作用

发布时间：2018-05-20 05:58

本文选题：家蚕 + 对乙酰氨基酚　；参考：《蚕业科学》2015年05期

【摘要】：以临床解热镇痛药基本成分对乙酰氨基酚(APAP)为模药,调查APAP在家蚕体内的代谢和对蚕体主要组织(系统)的损伤以及蚕体主要解毒酶基因的表达变化,探讨家蚕作为肝毒性药物毒理研究替代实验动物的可能性。家蚕5龄2 d幼虫经口给予APAP后0.5 h,在消化管、脂肪体和血淋巴中均能够检测到原药,APAP主要糖基化解毒代谢途径中的关键酶——尿苷二磷酸-葡萄糖醛酸基转移酶(UGT)活性也随即快速上升,其中脂肪体中的UGT酶活性上升早于血淋巴和消化管。实时荧光定量PCR(qRT-PCR)分析显示,幼虫消化管和脂肪体细胞中UGT家族基因Ugt30、Ugt86和Ugt89的转录水平在给予APAP后0.5 h开始显著上调。HE染色显示,高剂量APAP对蚕体消化管和脂肪体组织具有损伤作用,但AO/PI染色未发现血淋巴中死细胞增多。研究结果表明,家蚕的消化管、脂肪体和血淋巴都有通过糖基化代谢APAP的解毒功能,过量的APAP对消化管和脂肪体组织都有损伤作用。
[Abstract]:Taking the basic component of clinical antipyretic analgesics, acetaminophen (AP) as the model drug, the metabolism of APAP in Bombyx mori and the damage to the main tissue (system) of silkworm body and the expression of main detoxification enzyme gene in silkworm body were investigated. To explore the possibility of silkworm as a toxicology of hepatotoxic drugs to substitute experimental animals. The 5th instar 2nd day larvae of Bombyx mori were given APAP 0.5 h later in the digestive tract. The activity of uridine diphosphate glucuronyltransferase (UGTT), a key enzyme in the main glycosylation pathway of APAP, could be detected in both adipose body and hemolymph. The activity of UGT in fat body increased earlier than that in hemolymph and digestive tract. Real-time fluorescence quantitative analysis showed that the transcription levels of UGT family genes Ugt30, Ugt86 and Ugt89 in larval digestive tract and adipose cells began to upregulate significantly at 0.5 h after APAP administration. High dose APAP could damage the digestive tract and adipose tissue of silkworm, but no increase of dead cells in hemolymph was found by AO/PI staining. The results showed that the digestive tract, fat body and hemolymph of Bombyx mori had detoxification function by glycosylation metabolism of APAP, and excessive APAP could damage digestive duct and adipose tissue.
【作者单位】：苏州大学基础医学与生物科学学院;常州市第一人民医院;苏州大学心血管病研究所;苏州大学农业生物技术与生态研究院;
【基金】：国家自然科学基金项目(No.31472149) 国家高技术研究发展计划“863”重点项目(No.2011AA100306) 江苏省优势学科项目(No.YX11500211) 江苏省研究生培养创新工程项目(No.KYLX_1248)
【分类号】：R965

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