线粒体靶向小分子IR-61改善小鼠非酒精性脂肪肝

目的 探讨线粒体靶向七甲川花菁类荧光小分子IR-61对小鼠非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)模型的治疗效果.方法 通过喂养高脂饲料建立NAFLD小鼠模型,腹腔注射磷酸缓冲盐溶液(phosphate buffer saline,PBS)或IR-61,治疗18周后,取肝脏组织切片HE常规染色,显微镜下观察,采用酶比色法检测肝脏和血清甘油三酯(triglyceride,TG)含量,Real-time PCR和Western blot法检测固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP-1c)、乙酰辅酶A羧化酶1(acetyl-CoA carboxylase-1,ACC1)、过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptor-α,PPARα)和肉毒碱棕榈酰转移酶-1(carnitine palmitoyltransferase-1,CPT1)的mRNA及蛋白表达水平.结果 IR-61可降低高脂诱导的小鼠肝脏TG含量增加,抑制SREBP-1c、ACC1过度表达;同时增加肝脏PPARα、CPT1的表达(P ＜0.05);IR-61可明显改善小鼠肝脏的脂肪沉积.结论 IR-61通过抑制高脂诱导的脂肪合成代谢过度增强,促进肝脏脂肪酸氧化,减少肝脏甘油三酯沉积,从而改善非酒精性脂肪肝.

Effect of mitochondrial targeting small molecule IR-61 in attenuating non-alcoholic fatty liver in mice

Objective To investigate the therapeutic effect of IR-61,a mitochondrial targeting heptamethine cyanine dye,on non-alcoholic fatty liver disease (NAFLD) in a mouse model.Methods Mouse model of NAFLD was established by feeding the mice with a high-fat diet.After the modeling,the mice were treated with intraperitoneal injection of PBS or IR-61 (25 μL/g) once a week for 18 consecutive weeks.HE staining was used to observe the pathological changes in liver tissues,and liver and serum levels of triglyceride (TG) were measured using enzyme colorimetry.Real-time PCR and Western blotting were used to detect the expression levels of sterol regulatory element-binding protein-1c (SREBP-1c),acetyl-CoA carboxylase-1 (ACC1),peroxisome proliferator-activated receptor-α (PPARα) and carnitine palmitoyltransterase-1 (CPT1).Results IR-61 treatment reduced high-fat feeding-induced elevation of TG level in the liver of the mice and inhibited the high expression of SREBP-1c and ACC1.IR-61 significantly increased the expression of PPARα and CPT1 in the liver (P ＜ 0.05) and markedly improved fatty degeneration of the liver in mice after high-fat feeding.Conclusion IR-61 inhibits high-fat feeding-induced increase in fat synthesis,enhances liver fatty acid oxidation,and thereby reduces hepatic TG deposition and improves NAFLD in mice.