高压氧治疗对糖尿病大鼠末梢循环障碍与足部溃疡的疗效及其作用机制

Efficacy and mechanism of hyperbaric oxygen therapy on peripheral circulatory disorder and foot ulcers in diabetic rats

目的:探讨高压氧治疗对糖尿病大鼠末梢循环障碍与足部溃疡的疗效及其作用机制。方法:选取60只成年健康雄性SD大鼠,按照随机数字表法随机分为非糖尿病组、糖尿病假治疗组和高压氧治疗组,每组20只。注射2%链脲佐菌素建立糖尿病模型,以蒸气持续烫伤大鼠足底(面积约为37 mm 2)造成烫伤足溃疡模型。采用红外测温仪和足底测试仪分别测定大鼠双后足足底温度和热痛阈值,比较治疗前和治疗1、2、4周后3组大鼠的足底温度、足底热痛阈值。检测其创面组织中环氧化酶2(COX-2)、血管内皮生长因子(VEGF)、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)水平和丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平。结果:治疗前糖尿病假治疗组和高压氧治疗组大鼠的足底温度低于非糖尿病组(P<0.05);3组大鼠的足底温度治疗前后比较,差异无统计学意义(P>0.05);治疗1周后,糖尿病假治疗组和高压氧治疗组大鼠的足底温度低于非糖尿病组(P<0.05);治疗2周和4周后,糖尿病假治疗组大鼠的足底温度低于非糖尿病组和高压氧治疗组(P<0.05)。治疗前,糖尿病假治疗组和高压氧治疗组大鼠的足底热痛阈值高于非糖尿病组(P<0.05);治疗1周后,高压氧治疗组大鼠的足底热痛阈值低于治疗前,糖尿病假治疗组和高压氧治疗组高于非糖尿病组(P<0.05);治疗2周后,非糖尿病组和糖尿病假治疗组大鼠的足底热痛阈值较治疗前降低,高压氧治疗组高于非糖尿病组,低于糖尿病假治疗组(P<0.05);治疗4周后,非糖尿病组和高压氧治疗组大鼠的足底热痛阈值较治疗前降低,糖尿病假治疗组高于非糖尿病组和高压氧治疗组(P<0.05)。治疗前3组大鼠的创面面积比较差异无统计学意义(P>0.05);治疗1周后,3组大鼠的创面面积较治疗前显著增大,非糖尿病组和高压氧治疗组大于糖尿病假治疗组(P<0.05);治疗2周和4周后,3组大鼠的创面面积较治疗1周后显著减小,高压氧治疗组大于非糖尿病组,小于糖尿病假治疗组,差异均有统计学意义(P<0.05)。治疗后,高压氧治疗组大鼠创面组织中的COX-2水平低于糖尿病假治疗组,高于非糖尿病组(P<0.05);高压氧治疗组大鼠创面组织中的VEGF水平高于糖尿病假治疗组和非糖尿病组(P<0.05)。治疗后,高压氧治疗组大鼠的TNF-α、IL-6、IL-1β、hs-CRP水平低于糖尿病假治疗组,高于非糖尿病组(P<0.05)。治疗后,高压氧治疗组大鼠的SOD、MDA、CAT水平低于非糖尿病组,高于糖尿病假治疗组(P<0.05)。结论:高压氧可改善糖尿病足的足底温度和热痛阈值,降低COX-2水平、提高VEGF水平,减轻机体炎症和氧化应激反应,促进溃疡创面愈合,改善糖尿病末梢循环障碍,具有较好的临床应用价值。

Objective To study the efficacy and mechanism of hyperbaric oxygen therapy on peripheral circulation disorder and foot ulcer in diabetic rats.Methods A total of sixty adult healthy male SD rats were selected and randomly divided into non-diabetic group,diabetic sham treatment group,and hyperbaric oxygen treatment group,with 20 rats in each group.The diabetic model was established by injecting 2%streptozotocin,and the model of foot ulcer model was established by continuous scalding the rat’s left posterior sole with steam(with an area of about 37 mm2).An infrared thermometer was used to measure the temperature of the rats’two posterior soles,and a plantar tester was used to measure the rats’plantar thermal pain thresholds.The plantar temperatures and plantar thermal pain thresholds of the rats in the three groups were compared before treatment and after 1 week,2 weeks,and 4 weeks of treatment.The levels of cyclooxygenase 2(COX-2),vascular endothelial growth factor(VEGF),serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),hypersensitive C-reactive protein(hs-CRP),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)in wound tissue were detected.Results Before treatment,the plantar temperatures of the rats in the diabetic sham treatment group and the hyperbaric oxygen treatment group were lower than that in the non-diabetic group(P<0.05);there was no significant difference in the plantar temperature within each group before and after treatment(P>0.05).After 1 week of treatment,the plantar temperatures of the rats in the diabetic sham treatment group and the hyperbaric oxygen treatment group were lower than that in the non-diabetic group(P<0.05);after 2 and 4 weeks of treatment,the plantar temperature of the rats in the diabetic sham treatment group was lower than those in the non-diabetic group and the hyperbaric oxygen treatment group(P<0.05).Before treatment,the plantar thermal pain thresholds of the rats in the diabetic sham treatment group and the hyperbaric oxygen treatment group were higher than that in the non-diabetic group(P<0.05);after 1 week of treatment,the plantar thermal pain threshold of the rats in the hyperbaric oxygen treatment group was lower than that before treatment,and the plantar thermal pain thresholds of the rats in the diabetic sham treatment group and the hyperbaric oxygen treatment group were higher than that in the non-diabetic group(P<0.05);after 2 weeks of treatment,the plantar thermal pain thresholds of the rats in the non-diabetic group and the diabetic sham treatment group were lower than that before treatment,and the plantar thermal pain threshold of the rats in the hyperbaric oxygen treatment group was higher than that in the non-diabetic group but lower than that in the diabetic sham treatment group(P<0.05).After 4 weeks of treatment,the plantar thermal pain thresholds of the rats in the non-diabetic group and the hyperbaric oxygen treatment group were lower than that before treatment,and the plantar thermal pain threshold of the rats in the diabetic sham group was higher than those in the non-diabetic group and the hyperbaric oxygen treatment group(P<0.05).There was no significant difference in wound area among the three groups of rats before treatment(P>0.05).After 1 week of treatment,the wound areas in the three groups of rats were significantly increased compared with those before treatment,and the wound areas in the non-diabetic group and the hyperbaric oxygen treatment group were larger than that in the diabetic sham group(P<0.05).After 2 weeks and 4 weeks of treatment,the wound areas of the rats in the three groups were significantly reduced compared with those after 1 week of treatment,and the wound area of the rats in the hyperbaric oxygen treatment group was larger than that in the non-diabetic group but smaller than that in the diabetic sham treatment group,with statistically significant differences(P<0.05).After treatment,the level of COX-2 in wound tissue of the rats in the hyperbaric oxygen treatment group was lower than that in the diabetic sham treatment group but higher than that in the non-diabetic group(P<0.05);the level of VEGF in wound tissue of the rats in the hyperbaric oxygen treatment group was higher than those in the diabetic sham treatment group and the non-diabetic group(P<0.05).After treatment,the levels of TNF-α,IL-6,IL-1β,and hs-CRP of the rats in the hyperbaric oxygen treatment group were lower than those of the rats in the diabetic sham treatment group but higher than those in the non-diabetic group(P<0.05).After treatment,the levels of SOD,MDA,and CAT of the rats in the hyperbaric oxygen treatment group were lower than those in the non-diabetic group but higher than those in the diabetic sham treatment group(P<0.05).Conclusion Hyperbaric oxygen can improve the plantar temperature and thermal pain threshold of diabetic feet,reduce the level of COX-2,and increase the level of VEGF;meanwhile,it can reduce inflammation and oxidative stress reactions,promote ulcer wound healing,and improve peripheral circulation disorder.Thus it is of good clinical application value.