高压氧处理对糖尿病足溃疡大鼠创口愈合的影响及其作用机制

Effects of hyperbaric oxygenation on wound healing of foot ulcer in diabetic rats

目的探究高压氧(HBO)治疗对糖尿病足溃疡大鼠创口愈合的影响及其作用机制。方法60只SD大鼠完成糖尿病足溃疡造模后,按照数字表法随机分成模型组和HBO处理组,每组30只。对照组在干净的环境中静养,HBO组给予HBO治疗。在治疗的7、14、21 d观察2组大鼠创口愈合率,采用酶联免疫测定法检测大鼠外周血中炎性因子IL-6、IL-1β、TNF-α以及生长因子TGF-β、VEGF的表达水平。结果HBO组治疗7、14、21 d的愈合率分别为(17.4±1.77)%、(36.62±3.19)%和(78.27±8.19)%,模型组治疗7、14、21 d的愈合率分别为(8.89±1.23)%、(18.23±2.23)%和(42.11±4.47)%,2组比较差异均有统计学意义(均P<0.01)。HBO组治疗21 d后大鼠血清为(32.55±4.08)、(368.47±40.19)和(30.63±2.88)pg/ml,模型组HBO组治疗21 d后大鼠血清为(73.95±6.73)、(827.13±85.28)和(69.98±7.27)pg/ml,2组比较差异均有统计学意义(均P<0.01)。ELISA实验检测结果显示,与治疗前比较,HBO组和模型组糖尿病足溃疡大鼠外周血中7、14、21 d TGF-β、VEGF表达水平显著上调,差异均有统计学意义(均P<0.01)。与模型组比较,HBO组糖尿病足溃疡大鼠外周血中7、14、21 d TGF-β、VEGF部分表达水平显著上调,差异均有统计学意义(均P<0.05或P<0.01)。结论HBO处理可有效缓解糖尿病足溃疡大鼠免疫损伤,促进血管生成并促进肉芽组织生长,从而提高创口愈合率。

Objective To investigate the effects of hyperbaric oxygenation(HBO)on wound healing of foot ulcer in diabetic rats and possible mechanism involved.Methods Upon completion of the development of diabetic foot ulcer,60 SD rats were randomly divided into the model group(or control group)and the HBO treatment group,each consisting of 30 rats.The rats in the control group were left intact in the clean environment,while the rats in the HBO group were given HBO treatment.Seven,14 and 21 days after treatment,the rates of wound healing were observed in the 2 groups.The expression levels of inflammatory cytokines IL-6,IL-1β,TNF-α,TGF-βand VEGF in peripheral blood were detected by ELISA.Results Seven,14 and 21 days after treatment,the rates of wound healing for the HBO group were respectively(17.4±1.77)%,(36.62±3.19)%)and(78.27±8.19)%,while those of the model group were respectively(8.89±1.23)%,(18.23±2.23)%)and(42.11±4.47)%.There was statistical significance,when comparisons were made between them(all P<0.01).Twenty-one days after treatment,the serum levels of the rats in the HBO group were(32.55±4.08),(368.47±40.19)and(30.63±2.88)pg/ml,while those of the rats in the model group were respectively(73.95±6.73),(827.13±85.28)and(69.98±7.27)pg/ml.Statistical significance could be seen when comparisons were made between them(all P<0.01).ELISA detection results indicated that the expression levels of TGF-βand VEGF in peripheral blood,7,14 and 21 days after treatment in both groups were obviously up-regulated,as compared with those before treatment,and statistical significance could also be noted when comparisons were made between them(all P<0.01).The expression levels of TGF-βand VEGF in peripheral blood,7,14 and 21 days after treatment in the HBO group were also up-regulated to a certain extent,as compared with those of the model group,also with statistical significance(all P<0.05 or P<0.01).HBO therapy could significantly improve healing rate of foot ulcer in diabetic rats.At the same time,HBO therapy could significantly decrease the expression levels of IL-6,IL-1βand TNF-αin peripheral blood,and increase the expression levels of growth factors VEGF and TGF-β.Conclusion HBO treatment could effectively alleviate immune damage of the rats with diabetic foot ulcer,promote angiogenesis and granulation tissue growth,thereby significantly improving the rate of wound healing.