Therapeutic Effect Of Xianfang Huoming Decoction Against Hand-foot Syndrome Induced By Capecitabine

To investigate the therapeutic effect and mechanism of Xianfang Huoming Decoction against hand-foot syndrome by establishing and evaluating the rat model of hand foot syndrome induced by capecitabine.Firstly,We cultured Human immortalized keratinocyte in vitro(HACAT cells)to do Cytotoxicity test with fluorouracil,we found that the best dose of 5-Fu was 3.5ummol(about 1.5 ?L)when the cell survival rate was 50%.Setting cell culture hole with 1.8 ?L5-Fu,1.8 ?L 5-Fu+Xian Fang Huoming Yin liquid with concentration grad and Xian Fang Huoming Yin liquid with concentration grad respectively in subsequent cell culture experiments,cytotoxicity test(CCK8)was made 24 hours later to observe the effect on the cell survival rate.Then detected the content of cytokines in culture supernatant by enzyme-linked immunosorbent assay(ELISA).We found that the survival rate of the cellswas about 50% after the addition of 1.8 ?L5-Fu in the culture medium,the cell survival rate reached its peak with the only 4 ?L Xian Fang Huoming Yin liquid.Cell survival was the best when with 1.8 ?L5-Fu+4 ?L Xian Fang Huoming Yin liquid,and the survival rate was close to 100%.The Cytokine detection results showed that the expression of CNTF increased with the 1.8 ?L 5-Fu added inulture media,but the expression of PD-ECGF,CINC-3,IL-10,IL-? decreased.The expression of IL-10,CNTF decreased with the only 4?l Xian Fang Huoming Yin liquid.The expression of PD-ECGF,IL-?decreased,but the expression of CINC-3,CNTF,IL-10 significantly increased with 1.8 ?L 5-FU+4 ?L Xian Fang Huoming Yin liquid added in.Then establishing and evaluating the rat model of hand foot syndrome induced by capecitabine.115 SD female rats were selected and divided into six groups: a,b,c,d,e,f.Group a was given 200 mg/kg capecitabine by intragastric administration,twice a day,last 7 days,rest for 3 days.Group b was given 200 mg/kg capecitabine for another cycle on the basis of group a.Group c was given 400 mg/kg capecitabine by intragastric administration,twice a day,last 7 days,rest for 3 days,for 2 cycles.Group d and e was deionized water group.Group f was control group.Further more,to evaluated the model by comparing the image,He staining,sirius red staining.The results showed that incidence of HFS in group a was 40%,in group b was 77.5%,in group c was 80%.There was statistically significant difference in the incidence of HFS compared the group a with b and c(p <0.05).There was no significant difference in the incidence of HFS between the group b and the group c(p >0.05).The hand foot syndrome model can be established with 200mg/kg capecitabine for two cycles,2 times a day,7 days in a row,rest for 3 days,the state and stability of model is good,the success rate of the model is high(77.5%).Lastly,using Xianfang Huoming Decoction to intervene the rat model of HFS.150 SD female rats were selected for the research.The rat model of HFS that was established with 200 mg/kg capecitabine was selected to simulate HFS model with different dose.We prepared two kinds of animal models: group A(1 week)and group B(2 weeks),the model animals was respectively divided to four groups: group with oral l application of Xianfang Huoming Decoction(A1,B1),group with external use of Xianfang Huoming Decoction(A2,B2),group with urea vitamin E cream(A3,B3)and non treatment group(A4,B4),t-he intervening time was one week.Were collected the tissue of rats' hind foot plantar,and pro ducted paraffin section for HE staining,Sirius red staining and thymidine phosphorylase(TP)immunohistochemistry.On the other hand,we take serum to detect the content of CNTF,PD-ECGF,IL-?,IL-10 and CINC-3.The results showed that there was no significant difference in improvement rate of group A1,A2,A3 and A4,but the improvement rate of B2 was significantly higher than B1,B3,B4.No significant difference was found in the content of cytokines tested between the rats of symptoms improved and rats with no changes in A1,A2,A3,A4,but the expression of CINC-3 and CNTF of the rats of symptoms improved was lower than rats with no changes in B1,B2,B3,B4.There was no significant difference in the positive rate of TP expression between the improved rats after intervention,the no changed rats of after intervention and the control group rats of HFS(+)in group A,but which was higher than rats of HFS(-)in group A.There was no significant difference in the positive rate of TP expression between the improved rats after intervention,the no changed rats of after intervention and the control group rats of HFS(+)in group B,but which was higher than rats of HFS(-)in group B.In summary,the following conclusions can be drawn from this study: 1 Xianfang Huoming decoction can promote cell repair and antagonize the toxicity of 5-Fu toxicity.2 The high quality hand foot syndrome model can be established with 200mg/kg/time capecitabine for two cycles.3 The damage mechanism of damage-inflammatory response-damage is closely related to the occurrence of HFS.4 Xianfang Huoming decoction has good curative effect on treating HFS and the effect of oral is better than that of external.5 CNTF can be used as an indicator to predict the occurrence and the curative effect of the HFS.6 The results of TP immunohistochemistry showed that the higher positive rate of TP expression in the rats are more susceptible to HFS and Xianfang Huoming decoction has no effect on the expression of TP.7 In short time and low dose,stopping capecitabine can make clinical symptoms disappear,HFS must be given other interventions in the presence of long and large doses,the traditional medicine take the way of clearing heat and detoxicating,activating qi and activating blood circulation to treat the HFS is effectivethe,and the principle of treatment of modern medicine is antiinflammatory and the repair of nerve injury.