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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(P<0.01),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(P<0.01)。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。
Objective: To investigate the effects of cosolvent propanediol (PG) and HS 15 on paracetamol (APAP) -induced liver injury in mice. Methods: The model of hepatic injury was established by intraperitoneal injection of 300mg · kg -1 APAP. The levels of alanine aminotransferase, aspartate aminotransferase, glutathione in liver homogenate, And Western blot analysis were performed to compare the effects of pretreatment with PG (40%, v / v) and HS 15 on APAP-induced liver injury before modeling. The inhibitory effect of PG and HS 15 on CYP2E1 was investigated using in vitro mouse liver microsomal incubation test. Results: Pretreatment with PG for 7 days had the effect of lessening injury in APAP-induced liver injury model, while HS15 had no significant effect on APAP-induced liver injury model. Western blot results showed that, compared with the model group, the expression of CYP2E1 protein in PG pretreatment group had significant changes (P <0.01), while there was no significant difference in HS 15 group. In vitro enzymatic incubation experiments showed that 1% (v / v) PG significantly inhibited CYP2E1 (P <0.01). CONCLUSION: PG can interfere with APAP liver injury and is not suitable as a vehicle for APAP and related liver protection drugs. Its mechanism is related to the inhibition of CYP2E1 enzyme activity by PG. HS 15 has no obvious effect on this model and can be used as APAP liver injury study Solvents.