The Study Of Exercise Improve The Blood Supply In Patients With Diabetic Foot Ulcer Accompanied With Peripheral Arterial Disease And Exercise Induced Angiogenesis In Hind-limb Ischemic Diabetic Rats

Objective:1.Exercise prescription in patients with Diabetic foot ulcer(DFU)accompanied with Peripheral arterial disease(PAD)and its effect on foot perfusion and ulcer healing.2.To determine the effects of exercise on compensatory angiogenesis,as well as the the expression of Angiomotin and VEGF of diabetic rats ischemic skeletal muscle,in order to further clarify the relationship between both two of them and angiogenesis.Methods:Part1;60 randomly selected patients with DFU and PAD were divided into exercise group and control group.Patients in the exercise group had exercise therapy training,ensure that they can follow the exercise prescription,patients in the control group had no exercise requirements.12 weeks after the treatment,compared the two groups with ABI,TcPO2,skin temperature,BMI,HbA1c and the ulcer healing rate,evaluated satisfaction,compliance in the exercise group,and the adverse events of the treatment were recorded.Part 2:SD(Sprague Dawley)rats were randomly divided into four groups:normal group,ischemic rats group,diabetic rats group,diabetes and ischemic rats group.Every group further divided into ET group(Exercise training ET)and SED group(Sedentary SED).Rats in every group modeled and measured related indicators respectively before intervention as a baseline comparison.Rats in ET group were given intervention of treadmill exercise,rats in SED group unrestrained and kept in the cages.4 weeks laer,blood and skeletal muscle of rats were harvested.The capillaries density was detected using CD34 immunohistochemical,and the expression of Angiomotin and VEGF were measured by Western blotting method.Results:Part1:After the treatment of 12 weeks,in both of the two groups the ABI,TcPO2,foot skin temperature increased and HbA1c decreased,P<0.05.In the exercise group TcPO2 increased 5.25mmHg,skin temperature increased 0.45 ℃,BMI decreased 0.69,while in the control group TcPO2 increased 2.59mmHg,skin temperature increased 0.28℃,BMI increased 0.02,compared the value of index changes,P<0.01.The healing rate in the exercise group was 53.6%,while in the control group was 25.9%,P<0.05.Patients compliance and satisfaction to the exercise therapy is 90%,94%respectively.The incidence of adverse events in the exercise group had no causal relationship with the exercise prescription.Part2:1.Normal rats with hind limb ischemia had compensatory angiogenesis,characterized by increased capillary density in skeletal muscle,compared with non ischemia rats P<0.001,and associated with an increased expression of VEGF P<0.05,and the ratio of p80/p130 Amot increased P<0.001.2.The compensatory angiogenesis was restrained in diabetic rats,compared with non diabetic rats P<0.001.And associated with an increased expression of VEGF P<0.0001 and the ratio of p80/p130 Amot decreased P<0.001.3.After given the intervention of treadmill exercise,the capillary density of hind limb ischemia diabetic rats significantly increased,compared with non exercise group of hind limb ischemia diabetic rats P<0.001).And associated with an increased expression of VEGF P<0.001,and the ratio of p80/p130 Amot increased P<0.001.4.The ratio of p80/p130 Amot had a linear regression relationship between the skeletal muscle capillary density(R2 = 0.686,F =0.686,P<0.05).Conclusion:1.The exercise prescription in the study can improve the foot perfusion,and promote ulcer healing.It has the advantage of high safety,patient compliance and satisfaction.2.Exercise can conserve the compensatory angiogenesis in hind limbs ischemia diabetic rats.The increased expression of VEGF in diabetes can’t represent the increased angiogenesis.The ratio of p80/p130 Amot decreased in diabetes,and increased with exercise training.p80/p130Amot ratio can reflect the increased angiogenesis.