Studies have shown that liraglutide, or human umbilical cord mesenchymal stem cell (hUC-MSCs) can improve non-alcoholic fatty liver disease (NAFLD). However there have been no studies on the combination of the two used to treat NAFLD. This study aimed to explore the therapeutic effects of combination of liraglutide and hUC-MSCs on liver injury in rats with type 2 diabetes mellitus (T2DM) and NAFLD, and further investigate their mechanisms. Sprague Dawley rats fed by a high fat and high sucrose diet were randomly divided into 5 groups, including NC group, T2DM/NAFLD group, liraglutide group (treated with liraglutide, 200 μg/kg, twice daily for 8 weeks), hUC-MSCs group (treated with hUC-MSCs at the first and fifth weeks), liraglutid＋hUC-MSCs group (treated with liraglutide and hUC-MSCs). Liver tissue was procured for histological examination, real-time qRT-PCR and Western blot analysis. After treatment, liraglutide and hUC-MSCs reduced serum ALT and AST levels, alleviate liver inflammation and improved liver histopathology. The expressions of inflammatory cytokines, TLR4 and NF-κB in serum and liver were significantly inhibited, particularly in the combination treatment group. Eight weeks after liraglutide or hUC-MSCs administration, FBG, HbA1c, HOMA-IR, ALT, AST, Liver wet eight and hepatic TLR4, NF-κB, IL-6, TNF-α, 8-OHdG mRNA and proteins were significantly decreased, and the levels of SOD expression were significantly increased in three treatment groups compared with T2DM/NAFLD group. This study suggests that liraglutide in combination with hUC-MSCs could significantly improve glycolipid metabolism, insulin resistance and liver injury in T2DM/NAFLD rats. Its mechanism may be related to the down-regulation of the TLR4/NF-κB inflammatory pathway and improvement in oxidative stress.

研究表明，利拉鲁肽或人脐带间充质干细胞（hUC-MSC）可以改善非酒精性脂肪性肝病（NAFLD）。然而，尚未有关于用于治疗NAFLD的两者的组合的研究。本研究旨在探讨利拉鲁肽和hUC-MSCs联合治疗对2型糖尿病（T2DM）和NAFLD大鼠肝损伤的治疗作用，并进一步探讨其机制。高脂高蔗糖饮食喂养的Sprague Dawley大鼠随机分为5组，包括NC组，T2DM / NAFLD组，利拉鲁肽组（利拉鲁肽治疗，每天200μg/ kg，每天两次，连续8周），hUC-MSC组（在第1、5周用hUC-MSCs治疗），利拉鲁肽＋ hUC-MSCs组（用利拉鲁肽和hUC-MSCs治疗）。采购肝组织进行组织学检查，实时定量RT-PCR和蛋白质印迹分析。治疗后，利拉鲁肽和hUC-MSC可降低血清ALT和AST水平，减轻肝脏炎症并改善肝脏组织病理学。血清和肝脏中炎性细胞因子，TLR4和NF-κB的表达受到明显抑制，尤其是在联合治疗组中。利拉鲁肽或hUC-MSCs给药8周后，FBG，HbA1c，HOMA-IR，ALT，AST，肝湿8和肝TLR4，NF-κB，IL-6，TNF-α，8-OHdG mRNA和蛋白显着降低与T2DM / NAFLD组相比，三个治疗组的SOD表达水平显着增加。这项研究表明，利拉鲁肽与hUC-MSC联合可显着改善T2DM / NAFLD大鼠的糖脂代谢，胰岛素抵抗和肝损伤。