糖尿病性肝损伤中NADPH氧化酶NOX4的表达及意义OA

Mouse models of NAFLD and type 2 diabetes mellitus(T2DM)were established through high-fat diet feeding and high-fat diet feeding combined with intraperitoneal injection of streptozotocin(STZ),respectively.Twelve weeks after successful modeling,liver function tests,histopathological observations,and molecular biology techniques such as Western-blotting were performed.The experimental results showed that,compared to the normal group,the NAFLD and T2DM groups exhibited abnormal increases in liver function markers such as aspartate aminotransferase(AST)and alanine aminotransferase(ALT),significant liver enlargement,and typical fatty liver manifestations,including microvesicular steatosis and severe lipid deposition.Additionally,the levels of oxidative stress markers such as malondialdehyde(MDA)were significantly elevated in the liver tissues of diabetic mice.The degree of liver damage in the T2DM group was more severe than that in the NAFLD group.Mechanistic studies revealed that,compared to the normal and NAFLD groups,the expression of NADPH oxidase 4(NOX4)protein in the liver tissues of the T2DM group was significantly increased,accompanied by significant upregulation of mRNA expression of downstream inflammatory factors such as interleukin-6(IL-6)and interleukin-1β(IL-1β).This suggests that diabetes-induced upregulation of NOX4,leading to oxidative stress and inflammatory responses,is a critical factor in liver damage and the primary pathological mechanism underlying the exacerbation of NAFLD in diabetes.The findings of this study provide a theoretical basis for understanding the pathological mechanisms of diabetes-induced liver damage and exploring potential therapeutic targets.