Effect of Xiaozhongzhitong mixture on vascular regeneration of random flap in rats

AIM To observe the effect of Xiaozhongzhitong （detumescence and relieving pain） mixture on vascular regeneration and vascular endothelial growth factor （VEGF）-Dll4/Notch signaling pathway of random flap in rats. METHODS A total of 240 SD rats were randomly divided into 6 groups： blank group， sham group， model group， Xiaozhongzhitong mixture group （detumescence group）， Xiaozhongzhitong mixture+Notch blocker MK-0752 group （detumescence+MK group） and Xiaozhongzhitong mixture+VEGF receptor inhibitor axitinib group （detumescence+AXI group）. The capillary filling time， the number of new capillaries， the microvascular density， the microvascular diameter and the vascular survival area were observed by HE staining. The serum level of VEGF was measured by ELISA， and the mRNA expression of VEGFA， Notch and Dll4 in rat flap tissues was detected by RT-qPCR. RESULTS On the 10th day， compared with model group， the capillary filling time in detumescence group was decreased （P<0.05）. The capillary filling time in detumescence+AXI group was increased compared with detumescence group （P<0.05）. The flap tissue cells inmodel group were disordered and the nucleus was sparse， which showed obvious edema. Compared with model group， the number， diameter and area of microvessels， the serum content of VEGF， and the mRNA expression of VEGFA， Notch and Dll4 were significantly increased in detumescence group （P<0.05）. Compared with detumescence group， the number， density and area of microvessels， the serum content of VEGF， and the mRNA expression of VEGFA， notch and Dll4 was significantly decreased in detumescence+AXI group （P<0.05）. After the intervention with Notch blocker， the mRNA expression of VEGFA was increased， and the mRNA expression of Notch and Dll4 was inhibited （P<0.05）. CONCLUSION Xiaozhongzhitong mixture promotes the regeneration of blood vessels and enhances the survival rate of random flap， which may be related to the regulation of VEGF-Dll4/Notch signaling pathways.