槲皮素对T2DM小鼠代谢相关脂肪性肝损伤的保护

Protective Effects of Quercetin Against Metabolic-associated Fatty Liver Disease in Type 2 Diabetic Mice

目的探讨槲皮素对2型糖尿病(T2DM)小鼠代谢相关脂肪性肝病(MAFLD)的保护作用及其潜在机制。方法雄性C57BL/6J小鼠高脂饲料(HFD)喂养后注射链脲佐菌素(STZ)建立T2DM模型,随机分为糖尿病模型组(DM)和槲皮素干预组(DM+Qu),同时设正常对照组(Con)和槲皮素对照组(Qu)。小鼠分组喂养34周后处死,采血测定转氨酶,结合肝脏病理、qRT-PCR、超声和免疫组化等检测结果评价肝脏代谢应激性损伤程度及槲皮素干预效果。结果经槲皮素干预后,T2DM小鼠血清转氨酶ALT、AST水平下降(均P<0.05),脂质沉积及组织紊乱改善,p65蛋白及IL-1β、IL-6、TNF-α和TGF-βmRNA表达水平降低(均P<0.05),肝硬度显著下降(P<0.05),纤维化因子CTGF、α-SMA和collagenⅠ表达水平下降。结论槲皮素对T2DM小鼠肝脏损伤,尤其对纤维化具有良好的改善作用,其机制可能与槲皮素的抗炎活性有关。

Objective To investigate the protective effect of quercetin on metabolism-associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2 DM)mice and explore its possible mechanism.Methods Male C57 BL/6 J mice fed with high fat diet(HFD)combined with streptozotocin(STZ)were randomly divided into diabetic group(DM)and quercetin intervention group(DM+Qu).At the same time,normal control group(Con)and quercetin control group(Qu)were set.After feeding for 34 weeks,mice were sacrificed.Blood samples were collected for transaminase analysis.Liver pathological examination,qRT-PCR,ultrasound and immunohistochemistry were used to evaluate metabolic stress-induced liver injury and quercetin intervention effects.Results After quercetin intervention,serum ALT and AST levels of T2 DM mice decreased(both P<0.05),lipid deposition and tissue disorder were improved.Quercetin decreased protein expression of p65 and mRNA expression of IL-1β,IL-6,TNF-αand TGF-β(all P<0.05).A significant decrease on liver stiffness was observed(P<0.05).The expression levels of fibrosis factors CTGF,α-SMA and collagenⅠwere decreased.Conclusion Quercetin has a good protective effect on liver injury,especially fibrosis,in T2 DM mice,the mechanism of which may be related to its anti-inflammation activity.