| Objective: Pegylated liposomal doxorubicin has been widely used in the treatment of breast cancer,ovarian cancer and other tumors.Compared with ordinary anthracyclines,it has the characteristics of less curative effect and less adverse reactions,such as low cardiotoxicity and long half-life.But its hand-foot syndrome occurrence greatly limits its clinical application.This study aims to explore the experimental pathological mechanism of calcium dobesilate on the prevention and treatment of hand-foot syndrome induced by pegylated liposomal doxorubicin.Methods:1.Establishment of SD rat model of hand-foot syndrome induced by pegylated liposomal doxorubicin 7mg/kg tail vein injection.2.Divide 10 rats in the pegylated liposomal doxorubicin + calcium dobesilate gavage group into the experimental group,and 10 rats in the pegylated liposomal doxorubicin group for the control group.7 days after modeling,observe the changes in the skin tissue of the rat’s hind paws to see if there is any redness,scaling,ulcers,etc.and take pictures.The incidence of third-degree hand-foot syndrome in the hind paws of rats in the control group and the experimental group was counted.3.Observe the pathological changes of the hind paw skin of the control group and the experimental group under the light microscope.4.Comparatively observe the changes of the pore size of the vascular endothelial cells in the hind paws of the control group and the experimental group under the electron microscope.5.According to the ratio of the peak area of the test substance and the internal standard substance,the difference in the content of leaking doxorubicin in the skin tissue of the hind paw of the control group and the experimental group was measured.6.Calculate the content of Evans blue in the skin of the hind paws of rats in the control and experimental groups based on the absorbance,and compare the changes in vascular permeability between the two groups.Results:1.The incidence of third-degree hand-foot syndrome in the experimental group and the control group were 0 and 60%.2.Under the light microscope,it can be seen that the epidermal layer in the control group is thinned,the basal layer cells are swollen,vacuolar degeneration,and the stratum corneum is separated;the dermis is loose and edema,the blood vessels in the dermis are dilated,the blood vessel wall is thinned,and the number of capillary endothelial cells is reduced.Lymphocyte infiltration scattered around the blood vessels.However,the skin tissues of the hind paws of rats in the experimental group had lighter lesions.3.Comparing the pore size of capillary endothelial cells in the hind paw skin tissue of the experimental group and the control group under the scanning electron microscope.It can be seen that the capillary endothelial cell pore size in the hind paw skin tissue of the experimental group does not change significantly,while the control group The capillary endothelial pore size in the skin tissue of the hind paw of the rat was significantly enlarged.4.Determination of the average concentration of DOX leakage in the rat hind paw skin tissue of the experimental group of 11.466ug/g was significantly lower than the average concentration of 22.158ug/g in the control group,and the difference was statistically significant(P<0.05).5.Determine the concentration of Evans blue in the hind paw skin tissue of the experimental group and the control group.The exudative concentration of the experimental group was 4.652ug/ml lower than the 6.526ug/ml control group,and the difference was statistically significant(P<0.05).Conclusions:1.Calcium dobesilate can reduce the incidence of severe hand-foot syndrome caused by pegylated liposomal doxorubicin.2.Calcium dobesilate can improve the skin pathological changes of hand-foot syndrome caused by pegylated liposomal doxorubicin.3.Calcium dobesilate can protect the integrity of capillary endothelial cells,reduce the permeability of capillaries,and reduce the leakage of pegylated liposomal adriamycin in blood vessels. |
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