丙二醇与HS 15对对乙酰氨基酚致肝损伤模型的影响

发布时间：2019-02-24 13:51

【摘要】：目的:考察助溶剂丙二醇(PG)与HS 15对对乙酰氨基酚(APAP)肝损伤小鼠模型的影响。方法:采用腹腔注射300mg·kg~(-1)的APAP构建肝损伤小鼠模型,通过检测造模后血浆中谷丙转氨酶、谷草转氨酶水平、肝脏组织匀浆中谷胱甘肽含量、肝组织形态学及蛋白免疫印迹结果,分析比较造模前分别采用PG(40%,v/v)与HS 15预处理对APAP致肝损伤模型的影响。采用体外小鼠肝微粒体孵育试验考察PG与HS 15对CYP2E1的抑制作用。结果:PG预处理7 d对APAP致肝损伤模型具有减轻损伤作用,而HS15对APAP致肝损伤模型的构建无明显影响。蛋白免疫印迹结果表明,与模型组CYP2E1蛋白表达量相比,PG预处理组有显著变化(P0.01),而HS 15组无明显差别。体外酶孵育实验显示1%(v/v)PG对CYP2E1具有明显的抑制作用(P0.01)。结论:PG可干扰APAP肝损伤,不适合用作APAP及相关肝保护药物的溶媒,其机制与PG可抑制CYP2E1酶活性有关;HS 15对该模型无明显影响,可用作APAP肝损伤研究的溶媒。
[Abstract]:Aim: to investigate the effects of propanediol (PG) and HS 15 on the liver injury induced by paracetamol (APAP) in mice. Methods: the model of liver injury was established by intraperitoneal injection of 300mg kg~ (-1) APAP in mice. The levels of plasma alanine aminotransferase, glutamic oxaloacetic transaminase and glutathione in liver homogenate were measured. The effects of PG (40% v / v) and HS 15 on liver injury induced by APAP were analyzed and compared. The inhibitory effects of PG and HS 15 on CYP2E1 were investigated by mouse liver microsomal incubation in vitro. Results: PG pretreatment for 7 days could attenuate the liver injury induced by APAP, but HS15 had no effect on the construction of APAP induced liver injury model. The results of Western blot showed that the expression of CYP2E1 protein in PG pretreatment group was significantly different from that in model group (P0.01), but there was no significant difference in HS 15 group. In vitro enzyme incubation experiment showed that 1% (v / v) PG could inhibit CYP2E1 obviously (P0.01). Conclusion: PG can interfere with APAP liver injury and is not suitable for use as a solvent for APAP and related liver protection drugs. The mechanism is related to the inhibition of CYP2E1 enzyme activity by PG, and HS 15 has no obvious effect on this model, and can be used as a solvent for the study of APAP liver injury.
【作者单位】：华中科技大学同济医学院药学院;
【基金】：国家自然科学基金项目(编号:81302837) 中央高校基本科研业务费资助项目(编号:2016YXMS141)
【分类号】：R965

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