复方丹参滴丸调控VEGF、bFGF及circRNA表达促进糖尿病足小鼠创面愈合的机制研究OA

Objective It is to investigate the effect of Compound Danshen Dropping Pills(CDDP)on wound healing in diabetic foot mice and its regulatory role in the expressions of angiogenic factors and corresponding circular RNAs(circR-NAs).Methods Thirty male C57BL/6 mice were randomly divided into a normal group,a model group and a CDDP group,with 10 mice in each group.The mice of the model group and CDDP group were prepared with intraperitoneal injec-tion of streptozotocin(STZ)to establish models of diabetic foot,followed by the creation of a full-thickness skin excision wound on the dorsal midline of the mice.After operation,mupirocin ointment was topically applied daily for infection prophylaxis.Meanwhile,the mice in the CDDP group were given CDDP at a dose of 107 mg/(kg·d)via gavage,while the mice in the normal group and model group were given the same volume of normal saline via gavage,all once daily,con-tinuously treated for 12 days.The wound area and wound healing rate were calculated at different postoperative time points,the microvessel density and the plasma levels of vascular endothelial growth factor(VEGF)and basic fibroblast growth fac-tor(bFGF)in wound tissue were respectively detected by immunofluorescence assay and ELISA at different time points af-ter operation,the expressions of 10 circRNAs in plasma were detected by qRT-PCR on the 12th postoperative day.Results On postoperative days 4,8 and 12,the wound areas of mice in the CDDP group were significantly smaller(all P<0.05),and the wound healing rates were significantly higher than those in the model group at the corresponding time points(all P<0.05).The wound microvessel density and plasma levels of VEGF and bFGF of mice in the model group were all increased significantly on day 4 after operation,and then were gradually decreased with the extension of postoperative time,the diffe-rences were all statistically significant(all P<0.05);the wound microvessel density and plasma levels of VEGF and bFGF of mice in the CDDP group were all increased gradually with the extension of postoperative time,the differences were all statistically significant(all P<0.05);there were statistically significant differences in wound microvessel density,plasma levels of VEGF and bFGF of mice among the three groups at each postoperative time point(all P<0.05),specifically,the wound microvessel density on postoperative day 12,as well as the plasma levels of VEGF and bFGF on postoperative days 4,8 and 12 in the CDDP group were all significantly higher than those in the model group at the same time points(all P<0.05).Compared with the model group,the relative expressions of mmu_circ_0000250,mmu_circ_0001052,mmu_circ_0000101,mmu_circ_0001582,mmu_circ_0004423 in the CDDP group were significantly up-regulated(all P<0.05),while the relative expressions of mmu_circ_0005654,mmu_circ_0006475,mmu_circ_0003196,mmu_circ_0005785,mmu_circ_0003416 were significantly down-regulated(all P<0.05).Conclusion CDDP may promote angiogenesis via regula-ting the expressions of VEGF and bFGF,and modulate corresponding circRNAs to inhibit inflammation and fibrosis,im-prove endothelial cell function and delay cell apoptosis,thereby accelerating wound healing in diabetic foot.