Abstrakt

Preliminary exploration on the therapeutic effect of AGGF1 in mice with lower limb ischemia and corresponding molecular mechanism

Baohua Sun, Fangda Li, Jiang Shao, Bao Liu, Yu Chen, Changwei Liu, Yuehong Zheng

Objective: This study aimed to observe the therapeutic effect of angiogenic factor with G-patch and FHA domain 1 (AGGF1) in mice with lower limb ischemia and determine the corresponding molecular mechanism.

Methods: A total of 40 C57BL/6 male mice were selected. 32 mice were chosen to establish the lower limb ischemia model and divided into the low-dose, middle-dose, high-dose, and model groups. The remaining 8 mice comprised the sham-operation group and underwent separation of the left arteria femoralis and arteria iliaca externa (same with the model group). AGGF1 was injected once every day for 4 weeks. Tissue necrosis, dyskinesia scores, and recovery percentage of lower limb bloodstream at 1, 2, and 4 weeks after AGGF1 injection were compared. All mice were killed after 4 weeks of treatment. AGGF1, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) mRNA and protein levels in the musculus gastrocnemius at the operation side were measured and compared.

Results: Tissue necrosis and dyskinesia scores at 1, 2 and 4 weeks after AGGF1 injection and AGGF1, HIF-1α, and VEGF mRNA and protein levels in the musculus gastrocnemius of different groups were compared. The sham-operation group achieved the lowest values, followed by the middle-dose, highdose, low-dose, and model groups successively. Statistically significant differences between any two groups were found (P<0.05). Intra-group comparison revealed a slight change in the tissue necrosis score of the sham-operation group (P>0.05). The dyskinesia scores of the sham-operation group and the three dose groups sharply dropped as time passed (P<0.05), whereas those of the model group dramatically increased (P<0.05).

Conclusions: AGGF1 (2 μg/mL) can improve tissue necrosis and dyskinesia and accelerate lower limb bloodstream recovery of mice with lower limb ischemia. The mechanism is speculated to be related to an upregulated expression of AGGF1, HIF-1α, and VEGF mRNA and proteins.