不同强度跑步运动与二甲双胍联用对2型糖尿病并发骨质疏松大鼠的骨密度、骨吸收、胰岛素敏感性的影响效果研究

Effects of different intensity of running exercises combined with metformin on bone mineral density,bone metabolism,and insulin sensitivity in type 2 diabetic patients with osteoporosis

目的讨论不同运动强度跑步与二甲双胍联用对2型糖尿病并发骨质疏松(diabetic osteoporosis,DOP)模型大鼠骨密度、骨吸收、胰岛素敏感性的影响效果,为在运动处方与药物处方联用方案中药物使用和运动强度的合理制定提供依据。方法对120只SD大鼠购回后进行15 d适应性饲养。选取100只大鼠建立DOP动物模型,剩余20只大鼠正常饲养。检验DOP动物模型情况,建模成功的大鼠随机分为模型对照组(DM组)、二甲双胍组(metformin,MF组)、低强度跑步+二甲双胍组(LM组)、中强度跑步+二甲双胍组(MM组)、高强度跑步+二甲双胍组(HM组),正常饲养的20只大鼠为对照组(C组)。全部大鼠进行前测,内容包括骨密度(bone mineral density,BMD)、空腹血糖浓度(fasting plasma glucose,FPG)、空腹胰岛素水平(fasting insulin,FINS)、胰岛素抵抗指数(homeostasis model assessment insulin resistance,HOMA-IR)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesteroll,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesteroll,HDL-C)、抗酒石酸盐酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)、尿脱氧吡啶喏啉(deoxypyridinoline,DPD)、生物力学性能等指标。前测结束后,各组大鼠按计划进行为期12周的干预,干预结束后进行后测。结果大鼠体质量方面,在干预的第4、8、12周C组大鼠体质量显著高于DM组、LM组、MM组、HM组、MF组(P<0. 05),LM组大鼠体质量显著低于DM组(P<0. 05)。骨密度方面,LM组、MM组、HM组、MF组大鼠后测骨密度显著高于前测和DM组后测结果,但仍然明显低于C组(P<0. 05)。在骨代谢方面,LM组、MM组、HM组、MF组大鼠后测尿羟脯氨酸、尿DPD、血浆TRACP值显著高低于前测和DM组后测结果,但仍然明显高于C组(P<0. 05)。在糖代谢方面,LM组、MM组、HM组、MF组大鼠FPG、FINS后测值显著低于本组前测值、DM组和HM组后测结果,但明显高于C组(P<0. 05)。在胰岛素抵抗方面,MM组、HM组、MF组大鼠HOMA-IR后测值显著高低于本组前测值、MF组和HM组后测结果,但明显高于LM和MM组(P<0. 05)。在脂代谢方面,LM组、MM组、HM组、MF组大鼠甘油三酯(triglyceride,TG)、TC、LDL-C后测值显著低于本组前测值、DM组后测结果,但明显高于C组(P<0. 05)。LM组TG、TC、LDL-C指标后测值显著低于HM组、MF组(P<0. 05)。LM组、MM组、HM组、MF组大鼠HDL-C指标后测值显著高于本组前测值、DM组后测结果,但明显低于C组(P<0. 05)。结论二甲双胍搭配跑步的干预方案能够保持大鼠体重,降低血脂、血糖,缓解胰岛素抵抗,增加骨密度,减少骨吸收。其中二甲双胍搭配中低强度跑步方案在体重控制、降低血脂血糖、缓解胰岛素抵抗方面优于二甲双胍搭配高强度跑步方案。二甲双胍搭配高强度跑步方案对于2型糖尿病并发骨质疏松大鼠骨密度改善效果与二甲双胍搭配中低强度跑步方案相比具有优势。

Objective To investigate the effects of different intensity of running exercise combined with metformin on bone mineral density(BMD),bone metabolism,and insulin sensitivity in type 2 diabetic patients with osteoporosis(DOP),and to provide a basis for rational formulation of drug use and exercise intensity in a combination of exercise and drug prescription. Methods A total of 120 rats were adaptively fed for 15 days. Among those,100 rats were selected to establish the DOP animal model,and the remaining 20 rats were fed normally. The animal model of DOP was tested. The successfully modeled rats were randomly divided into model control group(DM group),metformin group(MF group),low intensity running + metformin group(LM group),medium intensity running +metformin group(MM group),and high-intensity running + metformin group(HM group).The remaining 20 rats were in the control group(group C). All the rats were pre-tested,including: BMD,fasting blood glucose concentration(FPG),fasting insulin level(FINS),insulin resistance index(HOMA-IR),TC,LDL-C,HDL-C,TRACP,DPD,biomechanical properties,and other indicators.After the pre-test,rats in each group were scheduled to undergo a 12-week intervention. Post-intervention test was performed after the intervention. Results In terms of body mass,the body weight of rats in group C was significantly higher than that in DM group,LM group,MM group,HM group,and MF group at the 4th,8th,and 12th week of intervention. The body mass of the rats in LM group was significantly lower than that of the DM group(P<0. 05). In terms of BMD,BMD in LM group,MM group,HM group,and MF group was significantly higher than that in the pre-test and DM groups,but it was still significantly lower than that in the C group(P<0. 05). In terms of bone metabolism,the urinary HOP,urine DPD,and plasma TRACP values in LM group,MM group,HM group,and MF group were significantly lower than those in the pre-test and DM groups,but still significantly higher than those in the C group(P<0. 05). In the aspect of glucose metabolism,the values of FPG and FINS in LM group,MM group,HM group,and MF group were significantly lower than those in the pre-test,DM group,and HM group,but significantly higher than those in group C. In the aspect of insulin resistance,HOMA-IR values in MM group,HM group,and MF group were significantly lower than those in the pretest,MF,and HM groups,but significantly higher than those in the LM and MM groups(P< 0. 05). In lipid metabolism,levels of TG,TC,and LDL-C in LM group,MM group,HM group,and MF group were significantly lower than those of the pre-test and DM group,but significantly higher than those in the C group(P<0. 05). The measured values of TG,TC,and LDL-C in LM group were significantly lower than those in HM group and MF group(P< 0. 05). The post-test values of HDL-C in LM group,MM group,HM group,and MF group were significantly higher than those in the pre-test and DM group,but significantly lower than those in group C(P<0. 05). Conclusion The treatment of metformin combined with running maintains the body weight,reduces blood lipids,blood glucose,relieve insulin resistances,increases BMD,and improves bone metabolism in rats. Metformin combined with low-intensity running program is superior to metformin combined with high-intensity running program in terms of weight control,lowering blood fat and blood glucose,and relieving insulin resistance. Metformin combined with high-intensity running program has an advantage in the improvement of BMD,comparing to metformin in combination with low-intensity running programs in type 2 diabetic rats with osteoporosis.