Abstract: In this study, we successfully established mouse and canine diabetes models under the combined effect of high-fat diet (HFD) feeding and streptozotocin (STZ) injecting, aiming to investigate the effect and mechanism of Mitoquionl Mesylate (MitoQ) pretreatment of adipose-derived mesenchymal stem cells (ADMSCs) in enhancing the therapeutic effect of diabetic animal models. At the cellular level, ADMSCs in normal culture were pretreated with MitoQ at a concentration of 1 μmol·L^-1 in α-MEM+ cell culture medium, and the morphological changes, growth, proliferation, migration and antioxidant capacity of MitoQ-ADMSCs and ADMSCs were examined respectively. At the animal level, forty-eight 8-week old Kun-Ming(KM) male mice and 12 Chinese Field canines were selected and randomly divided into 4 groups:normal control group (NC group), diabetes model group (Diabetes group), ADMSCs treatment group alone (ADMSCs group) and combined treatment group of MitoQ pretreated ADMSCs (MitoQ-ADMSCs group). Diabetes models were made in mice and canines except for the NC group, the animals in the ADMSCs and MitoQ-ADMSCs groups were transplanted with 2×10⁶ cells each mice, and 1×10⁷ cells each canines once a week, for 3 consecutive weeks. Changes in clinical indicators were continuously monitored during modeling and treatment, and samples were collected 1 week after treatment and analyzed for serological levels, histological levels, oxidative stress levels and serum metabolomic changes in canines. The results showed that MitoQ treatment of ADMSCs did not affect their cell morphology, but could promote their growth, proliferation and migration ability, as well as enhance their antioxidant and anti-aging abilities. The treatment of ADMSCs and After transplantation of ADMSCs and MitoQ-ADMSCs, it was found that MitoQ significantly promoted the ability of ADMSCs to lower blood glucose, and improved pancreatic β-cell function and the body's blood glucose regulation ability. Staining of pancreatic and liver tissues revealed that ADMSCs could reduce tissue damage, promote insulin secretion, and reduce impaired hepatic glycogen synthesis and fibrosis levels, however the effects were limited, while MitoQ was able to enhance these effects more significantly. Detection of indicators related to oxidative stress in pancreatic tissues showed that MitoQ treatment of ADMSCs could effectively enhance antioxidant capacity of the body and reduce oxidative damage, thus enhancing the therapeutic effect. Metabolomic analysis of canine serum revealed that MitoQ treatment of ADMSCs significantly promoted the expression of antioxidant-related metabolites in the body. The results revealed that MitoQ could improve the antioxidant capacity of ADMSCs and accelerate the repair of tissue damage resulted from diabetes, thus beneficial for the treating of metabolism diseases in mice and canines.

Key words: mitoquionl mesylate, adipose-derived mesenchymal stem cells, canine, diabetes