益气化瘀方调控PI3K/AKT/mTOR信号通路对糖尿病溃疡大鼠周围神经病变和创面愈合的影响

Effect of Yiqi Huayu Decoction on PI3K/AKT/mTOR Signal Pathway on Peripheral Neuropathy and Wound Healing in Rats with Diabetic Ulcer

目的探讨益气化瘀方对糖尿病溃疡大鼠周围神经病变和创面愈合的影响。方法健康雄性(SPF级)SD大鼠170只,设正常对照组(34只),另136只大鼠建立糖尿病周围神经病变溃疡模型,随机分为模型组、益气化瘀方组、益气化瘀方+PI3K抑制剂组、益气化瘀方+mTOR抑制剂组。观察给药后第1、2、3、4、5周大鼠体重、血糖、热水甩尾潜伏期、步态和简易机械性痛阈,第3、7、14、21天大鼠神经传导速度、创面愈合率和平均愈合时间。结果与正常对照组比较,模型组体重减轻,血糖升高,甩尾潜伏期延长,跛行,机械性痛阈升高,神经传导速度减慢,创面愈合率降低,愈合时间延长(P<0.05或P<0.01);与模型组比较,益气化瘀方组大鼠体重增加,血糖降低,甩尾潜伏期缩短,机械性痛阈降低,神经传导速度加快,创面愈合率升高,愈合时间缩短(P<0.05或P<0.01);与益气化瘀方组比较,益气化瘀方+PI3K抑制剂组、益气化瘀方+mTOR抑制剂组血糖升高,体重减轻,甩尾潜伏期延长,跛行,机械性痛阈升高,神经传导速度降低,创面愈合率降低,愈合时间延长(P<0.05或P<0.01)。结论益气化瘀方可能通过调控PI3K/AKT/mTOR信号通路,改善糖尿病溃疡大鼠周围神经病变,促进溃疡创面愈合。

Objective To investigate the effect of Yiqi Huayu Decoction on peripheral neuropathy and wound healing in rats with diabetic ulcer.Methods 34 healthy male(SPF grade)SD rats were set as normal control group,and the other 136 rats were established a diabetic ulcer model with peripheral neuropathy,then randomly divided into model group,Yiqi Huayu Decoction group,Yiqi Huayu Decoction+PI3 K inhibitor group,Yiqi Huayu Decoction+mTOR inhibitor group.Observe rats’weight,blood sugar,hot water tail flick latency,gait and simple mechanical pain threshold at 1-5 weeks after administration,and rat nerve conduction velocity,wound healing rate and average healing time at day3,7,14 and 21 after administration.Results Compared with the control group,the model group have lower weight,higher blood sugar,extended tail-flick latency,limp,higher mechanical pain threshold,slower nerve conduction velocity,lower wound healing rate,and longer healing time(P<0.05 or P<0.01);Compared with the model group,rats in the Yiqi Huayu Decoction group have higher weight,lower blood sugar,shortened tail-flick latency,lower mechanical pain threshold,faster nerve conduction speed,higher wound healing rate,and shorter healing time(P<0.05 or P<0.01);Compared with the Yiqi Huayu Decoction group,both the Yiqi Huayu Decoction+PI3 K inhibitor group and the Yiqi Huayu Decoction+mTOR inhibitor group have higher blood sugar,lower weight,longer tail flick latency,limp,higher mechanical pain threshold,slower nerve conduction velocity,lower wound healing rate,and longer healing time(P<0.05 or P<0.01).Conclusion Yiqi Huayu Decoction may improve the peripheral neuropathy of rats with diabetic ulcer and promote the healing of ulcer wounds by regulating the PI3 K/AKT/mTOR signal pathway.