Research Of Effect And Mechanism Of Yan Hu Suo Mixture-1on Pirarubicin-induced Extravasation Injury And Phlebitis

Objective:The effect and mechanism of Yan Hu Suo Mixture-1(YHS-1) on pirarubicin-induced extravasation injury and phlebitis were investigated. The study provided the basis for clinical application of YHS-1.Methods:Kunming mice were randomly divided into three groups by pirarubicin concentrations of2.25g/L,2g/L,1.75g/L. Rabbits were divided into three groups by concentrations of0.5g/L,1.0g/L,1.5g/L. The appropriate concentrations were selected. Kunming mice pirarubicin extravasation injury models and rabbits ear vein phlebitis were established. Chinese medicine, Yan Hu Suo Mixture-1, has preventive effects on chemotherapy-induced extravasation injuries and phlebitis. Extravasation injury models were divided into YHS-1group A, Ruyi Golden Powder group, YHS-1group B and control group. The area of extravasation lesion was measured. The degree and healing time of injury was recorded. The lesion tissues were resected from one mouse in each group on the dl,4,7,11,18after extravasation. Pathological manifestations were observed after HE staining. The expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) were detected by immunohistochemistry. Rabbite models were divided into YHS-1group, sulfate group and control group. The occurrence and healing time of phlebitis were observed. Histopathologic slide and HE staining of local vein and peripheral tissue were carried out at48th hour and7th day after intervention. Pathologic damage and healing state of vein and peripheral tissue were examined. Expression of VEGF and intercellular adhesion molecule-1(ICAM-1) in the vein and peripheral tissue were detected by immunohistochemistry.Results:In the extravasation injury study, the area and the degree of extravasation injury of the YHS-1group A, Ruyi Golden Powder group and YHS-1group B were less than those of the concrol group (P<0.05). The mice in YHS-1group A had the smallest injury area and the shortest healing time. Moreover, they showed slighter tissue injuries, delayed ulceration and earlier tissue repairment by Pathological morphology. In addition, the VEGF and EGFR expression of YHS-1group A were higher than those of the control group. In the phlebitis study, compared with control group, the degree of phlebitis was significantly milder and the healing time was shorter in YHS-1group and sulfate group. Pathological morphology showed acute and chronic inflammation. The expression of VEGF were higher and the expression of ICAM-1were lower in the vein and peripheral tissue.Conclusion:The preventive and therapeutic effects of YHS-1on Kunming mice pirarubicin-induced extravasation injury and rabbits ear vein phlebitis are satisfactory, better than Ruyi golden powder and sulfate. It may be associated with the up-regulation of VEGF and EGFR expression and fibrous tissue proliferation in extravasation injury area. The mechanism of protecting chemotherapy phlebitis is probably related with increasing the expression of VEGF, promoting the proliferation and repairment of endothelial cells, reducing the expression of ICAM-1and lightening the local inflammatory response.