Effect Of Vibration Exercise Combined Astragalus Injection On Chemotherapy-related Fatigue In Female Rats With Breast Cancer

ObjectiveTo establish a model of Chemotherapy-related fatigue(CRF)in female SD rats with similar symptoms to clinical patient.To investigate the effects of vibration exercise combined astragalus Injection on CRF and its possible preliminary mechanism by observing the general condition,body weight,behavioral experiments(rat tail suspension experiment,exhaustive swimming test)and detecting serum levels of IL-1?,TNF-? and IL-6.Provide a new direction and ideas for the treatment of CRF.Furthermore,provide basic research and basic theoretical for clinical treatment and nursing of CRF in the future,improve the quality of nursing care for breast cancer treatment.MethodsEighty female SD rats,body weight 100~120g,adaptive fed for 7 days and 5min/d swimming training were carried out during the last 3 days,were randomly divided into a normal control group(N,8 rats)and an experiment group.The rats in the experiment group establish a model of chemotherapy related fatigue.0.2ml SHZ-88 in logarithmic growth phase(5×107cells/ml)was inoculated subcutaneously into the right side of the second breast fat pad near armpit of each female rat.Rats with single tumor block,0.5cm3~0.8cm3 or so,without ulceration of the surface skin,without fur shedding were selected and were randomly divided into a model group(M),astragalus group(H),low frequency short time group(LS),medium frequency long time group(ML),LS+ astragalus group(LS+H),ML+ astragalus group(ML+H),8 rats in each group;above of 6 groups received intraperitoneal injection of epirubicin hydrochloride(2.5mg/kg,3 consecutive days,6 day intervals)at a cumulative does of 15mg/kg to establish a model of CRF.Group of LS,LS+H and ML,ML+H were respectively administrated to vibration exercise for 15 Hz,10min(5min×2,intermittent 10min),2mm and 25 Hz,30min(15min×2,intermittent 10min),2mm;1 times a day and 1 day rest after 6 days for 4 weeks.Treatment group involving astragalus(H,LS+H,ML+H)received intraperitoneal injection of astragalus of 4g/kg/d before vibration exercise and for 4 weeks.The rest of the groups were given the corresponding volume of normal.In the course of the experiment,the general condition of the rats was observed,and the weight was measured every week;after a tumor-burdened(1 day before chemotherapy administration),after chemotherapy(24 hours after the last drug administration)and after treatment(1 day before blood collection),the immobility time of tail suspension test(TST)and exhaustive swimming test(EST)were carried out to evaluate the status of CRF;after the last administration of astragalus 30 min and(or)vibration exercise,blood samples were obtained from abdominal aorta immediately to detect serum levels of IL-1?,TNF-? and IL-6.Results1.The general state: Before chemotherapy,color and integrity of the fur,auricle and mucosa,drinking,food intake,mental state,activity,responses to stimuli of rats were no obvious difference in each group.Rats in 7 groups with smooth and shiny fur,ruddy auricle,mucosa integrity without ulceration,active drinking and feeding,mental state better,lively and happy to move to avoid stimulation.During the whole experiment,no significant change was mentioned in the N group.After chemotherapy,compared with the N group,the rest 6 groups of rats appeared fur lackluster,individual lower abdominal damp and hair removal,pale auricle,nasal,inner canthus and urethral opening bleeding,drinking and food intake reduced,depressed and less dynamic,unresponsive to stimuli not dodge and so on.At the end of experiment,the general condition of the six groups of rats from relatively good to bad as follows: ML+H,LS+H,H,ML,LS,M.2.Body weight: After the tumor bearing,compared the body weight of female rats of each group,there was no significant difference(P>0.05)between the two groups.After chemotherapy,the body weight of female rats in groups of M,H,LS,ML,LS+H,ML+H were lower than that in the group of N(P<0.01);compared with group of M,the body weight of female rats in groups of H,LS,ML,LS+H,ML+H were no significant difference(P>0.05).After the intervention,the body weight of female rats in groups of M,H,LS,ML,LS+H,ML+H were lower than that in the group of N(P<0.01);the body weight of female rats in groups of H,LS+H,ML+H were higher than that in M group(P<0.05),but,compared with the M group,there were no significant difference in groups of LS and ML(P>0.05).3.Tail suspension test(TST): After the tumor bearing,compared the immobility time of TST of each group,there was no significant difference(P>0.05)between the two groups.After chemotherapy,the immobility time of TST in groups of M,H,LS,ML,LS+H,ML+H were higher than that in the group of N(P<0.01);compared with group of M,the immobility time of TST in groups of H,LS,ML,LS+H,ML+H were no significant difference(P>0.05).After the intervention,the immobility time of TST in groups of M,H,LS,ML,LS+H,ML+H were higher than these in the group of N(P<0.01);the immobility time of TST in groups of H,ML,LS+H,ML+H were lower than that in the group of M(P<0.05,P<0.01).4.Exhaustive swimming test(EST): After the tumor bearing,compared the time of EST of each group,there was no significant difference(P>0.05)between the two groups.After chemotherapy,the time of EST in groups of M,H,LS,ML,LS+H,ML+H were lower than that in the group of N(P<0.01);compared with group of M,the time of EST in groups of H,LS,ML,LS+H,ML+H were no significant difference(P>0.05).After the intervention,the time of EST in groups of M,H,LS,ML,LS+H,ML+H were lower than these in the group of N(P<0.01);the time of EST in groups of H,ML,LS+H,ML+H were higher than that in the group of M(P<0.05,P<0.01).5.The serum level of IL-1? of rats: The serum level of IL-1? of rats in M,H,LS,ML,LS+H,ML+H groups were higher than that in the N group(P<0.01);the serum level of IL-1? of rats in ML,LS+H,ML+H groups were lower than that in the M group(P<0.05,P<0.01),however,compared with the M group,the serum level of IL-1? of rats in groups of H and LS were no significant difference(P>0.05).6.The serum level of TNF-? of rats: The serum level of TNF-? of rats in M,H,LS,ML,LS+H groups were higher than that in the N group(P<0.05,P<0.01),and was no significant difference in the ML+H group(P>0.05)which compared with the N group;the serum level of TNF-? of rats in ML,LS+H,ML+H groups were lower than that in the M group(P<0.05,P<0.01),however,compared with the group of M,the serum level of TNF-? of rats in the H and LS groups were no significant difference(P>0.05).7.The serum level of IL-6 of rats: Compared the serum level of IL-6 of rats,there were no significant difference among the groups of N,M,H(P>0.05);the serum level of IL-6 of rats in ML(P<0.05),LS+H(P<0.05),ML+H(P<0.01)groups were higher than that in the M group;the serum level of IL-6 of rats in ML(P<0.05),LS+H(P<0.05),ML+H(P<0.01)groups were higher than that in the H group.Conclusions1.Female rats with SHZ-88 received Epirubicin hydrochloride which belongs to anthracyclines to establish a rat model of breast cancer chemotherapy related fatigue was possible.The degree of fatigue uniformity,long duration,consistent with the characteristics of the clinical symptoms of CRF,easy to operate,suitable for breast cancer CRF related research.2.Cytotoxicity of anthracycline-based regimens of epirubicin hydrochloride up-regulation of inflammatory cytokines of IL-1? and TNF-? in serum may be one of the potential causes of the occurrence of CRF.3.Vibration exercise combined astragalus injection caused synergistic anti CRF effects.4.Down-regulation of inflammatory cytokines,up-regulation of anti-inflammatory cytokines may be one of the potential mechanisms for vibration exercise combined astragalus injection reducing CRF in female rats.