中低强度跑台运动结合低频振动干预对阿霉素诱发的心脏毒性作用和骨质疏松的影响研究

Effects of moderate-low intensity treadmill exercise combined with low frequency vibration intervention on doxorubicin-induced cardiotoxicity and osteoporosis

目的探讨运动干预对于阿霉素引发的机体性毒性和骨质疏松的影响效果,为具有癌症患者体适能的恢复制定具有可操作性的运动处方提供理论参考。方法本研究采用50只小鼠,将所有小鼠进行1周的适应性喂养并在这一周内对小鼠骨密度和骨质代谢进行前测(骨密度、骨质代谢);对小鼠进行分组:安静对照组(control group,C组,n=10)、阿霉素对照组(Dox group,D组,n=10)、跑台运动+阿霉素组(run+Dox group,RD组,n=10)、振动训练+阿霉素组(vibration+Dox group,VD组,n=10)、跑台+振动+阿霉素组(run+vibration+Dox group,RVD组,n=10)组,RD组、VD组、RVD组开始执行运动方案,C组和D组小鼠在笼内正常喂养活动;在D组、RD组、VD组、RVD组在进行运动干预的第15天开始,每天腹腔注射方式对小鼠进行Dox给药,连续10 d。C组小鼠在同一周期内每日注射等量的生理盐水,整个实验周期为8周,8周后进行后测(骨密度、骨质代谢、心脏超声波图像、心脏功能)。结果心室后壁收缩(PWs)、心脏后壁舒张(PWd)指标,D组心室厚度显著低于C组,RD组、VD组厚度显著高于D组,且显著低于C组;RVD组心室厚度显著高于D组。心室间隔收缩(IVSs)指标、D组心室厚度显著低于C组,RD组、VD组厚度显著高于D组,且显著低于C组后壁舒张;心室中膈壁舒张厚度(IVSs),心室内径收缩(IDs),心脏收缩时心室壁相对厚度(RWTs)各组差异不具有统计学意义。骨密度指标D组、RD组、VD组后测结果显著低于前测。C组、RVD组后测与前测差异不具有统计学意义。D组后测结果显著低于C组。RD组、VD组后测结果显著高于D组,且显著低于C组;RVD组后测结果显著大于D组。Ca^(2+)、ALP、BGP、TRACP5b指标,D组、RD组、VD组、RVD组后测结果显著高于前测。D组后测结果显著低于C组,RD组、VD组后测结果显著低于D组,且显著高于C组;RVD组后测结果显著低于D组、RD组、VD组、显著高于C组。结论低强度跑步运动结合低强度振动训练对于利用阿霉素进行治疗的癌症患者具有较高的可操作性,且其能够对阿霉素诱发的骨质疏松具有较好预防和治疗作用。

Objective To investigate the effect of exercise intervention on the toxic effect and osteoporosis induced by doxorubicin, and to provide a theoretical reference for the development of a practical exercise prescription for the recovery of fitness in cancer patients. Methods In this study, 50 mice were used. All the mice were fed adaptively for 1 week. Bone mineral density(BMD) and bone metabolism were measured during this week. Mice were divided into control group(group C, n=10), doxorubicin control group(DOX group, group D, n=10), treadmill exercise + doxorubicin group(Run+Dox group, RD group, n=10), vibration training + adriamycin group(vibration+dox group, VD group, n=10), and treadmill+vibration + doxorubicin group(Run + Vibration+Dox group, RVD group, n=10). Mice in RD group, VD group, and RVD group started exercise program. Mice in C group and D group were fed normally in cages. Mice in D group, RD group, VD group, and RVD group received daily intraperitoneal injection of DOX on the 15 th day of exercise intervention, and lasted for 10 consecutive days. Mice in group C were injected with the same amount of normal saline in the same cycle. The whole experiment period was 8 weeks. BMD, bone metabolism, cardiac ultrasound images, and heart function were measured after 8 weeks. Results Ventricular posterior wall contraction(PWs), posterior wall diastolic(PWd) index, ventricular thickness in group D was significantly lower than those in group C(P<0.05). The thickness in RD group and VD group was significantly higher than that in group D(P<0.05), but was significantly lower than in C group(P<0.05). The ventricular thickness in RVD group was significantly higher than that in D group(P<0.05). Ventricular septal contraction(IVSs) index and the ventricular thickness in group D were significantly lower than those in group C and RD group(P<0.05). The thickness in VD group was significantly higher than that in group D(P<0.05), but was significantly lower than that in group C in posterior wall dilation(P<0.05), ventricular diastolic thickness(IVSs) in the ventricle, ventricular contractions(IDs), ventricular diastolic(IDs), ventricular wall relative thickness(RWTs) during systole, and ventricular relative thickness(RWTs) during diastole. The post-test results of bone mineral density was significantly lower in group D, RD, and VD than those before the test(P<0.05). There was no significant difference between post-test and pretest in group C and RVD(P>0.05). The post-test results in group D were significantly lower than those in group C(P<0.05). The post-test results in RD group and group VD were significantly higher than group D(P<0.05), but significantly lower than group C(P<0.05). The post-test results of RVD group were significantly higher than D group. The post-test results of Ca, ALP, BGP, and TRACP5 b in group D, RD group, VD group, and RVD group were significantly higher than those before the test(P<0.05). The post-test results of group D were significantly lower than those in group C(P<0.05). The post-test results of RD group and VD group were significantly lower than those in group D(P<0.05), but significantly higher than those in group C(P<0.05). Post-test results in RVD group were significantly lower than those in D group, RD group, and VD group(P<0.05), but significantly higher than in C group(P<0.05). Conclusion The use of doxorubicin may lead to thinning of heart wall, decrease of blood flow in the heart, decrease of BMD, and increase of bone resorption in the mice. Treadmill and vibration intervention inhibit the thinness of the left ventricular wall and the decrease of blood flow in the heart induced by doxorubicin in a certain extent. Treadmill combined with vibration intervention significantly inhibit adriamycin-induced decrease of left ventricular wall thickness and cardiac blood flow in mice. Low-intensity running exercises combined with low-intensity vibration training has high operability for cancer patients treated with doxorubicin, and good preventive and therapeutic effect on doxorubicin-induced osteoporosis.