【摘要】：目的:考察助溶劑丙二醇(PG)與HS 15對(duì)對(duì)乙酰氨基酚(APAP)肝損傷小鼠模型的影響。方法:采用腹腔注射300mg·kg~(-1)的APAP構(gòu)建肝損傷小鼠模型,通過(guò)檢測(cè)造模后血漿中谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶水平、肝臟組織勻漿中谷胱甘肽含量、肝組織形態(tài)學(xué)及蛋白免疫印跡結(jié)果,分析比較造模前分別采用PG(40%,v/v)與HS 15預(yù)處理對(duì)APAP致肝損傷模型的影響。采用體外小鼠肝微粒體孵育試驗(yàn)考察PG與HS 15對(duì)CYP2E1的抑制作用。結(jié)果:PG預(yù)處理7 d對(duì)APAP致肝損傷模型具有減輕損傷作用,而HS15對(duì)APAP致肝損傷模型的構(gòu)建無(wú)明顯影響。蛋白免疫印跡結(jié)果表明,與模型組CYP2E1蛋白表達(dá)量相比,PG預(yù)處理組有顯著變化(P0.01),而HS 15組無(wú)明顯差別。體外酶孵育實(shí)驗(yàn)顯示1%(v/v)PG對(duì)CYP2E1具有明顯的抑制作用(P0.01)。結(jié)論:PG可干擾APAP肝損傷,不適合用作APAP及相關(guān)肝保護(hù)藥物的溶媒,其機(jī)制與PG可抑制CYP2E1酶活性有關(guān);HS 15對(duì)該模型無(wú)明顯影響,可用作APAP肝損傷研究的溶媒。
[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.
【作者單位】： 華中科技大學(xué)同濟(jì)醫(yī)學(xué)院藥學(xué)院;
【基金】：國(guó)家自然科學(xué)基金項(xiàng)目(編號(hào):81302837) 中央高�；究蒲袠I(yè)務(wù)費(fèi)資助項(xiàng)目(編號(hào):2016YXMS141)
【分類號(hào)】：R965

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