高压氧通过调节细胞因子水平改善链脲佐菌素糖尿病大鼠周围神经病变的实验研究

Hyperbaric oxygenation improving the peripheral neuropathy in STZ-diabetic rats through regulating cytokines

目的:研究高压氧治疗(HBOT)是否可改善STZ糖尿病大鼠的周围神经病变并探讨其机制。方法:将链脲佐菌素(STZ)糖尿病大鼠随机分为2组。HBOT组(n=31):每天接受0.15MPaHBOT1h,连续20天。糖尿病组(n=32):不做治疗。正常组(n=20):正常SD大鼠。分别在疗程10天、20天时测定右后肢胫神经、腓神经的传导速度(NCV)后处死治疗组及同期对照组大鼠,取动脉血用ELISA法和硝酸还原酶法测定3组血清NGF、IGF-1、NO和MMP-1水平。结果:治疗前糖尿病大鼠的胫腓神经的NCV明显低于正常组。HBO治疗10d后,治疗组后肢胫神经和腓神经的传导速度明显高于同期糖尿病组(P<0.05),但低于正常组;血清MMP-1水平明显降低,血清NGF、NO水平稍有增高,但与糖尿病组比较差异无显著性意义。20d后,治疗组后肢神经的传导速度明显高于同期糖尿病组(P<0.01),而与正常组间差异无显著性意义(P>0.05);治疗组雪旺细胞数明显增多,超微结构的异常如神经髓鞘纤维化增厚、轴索缩小变性等得到明显改善;血清NGF和NO水平显著高于糖尿病组(P<0.01),治疗组血IGF-1水平显著高于糖尿病组(P<0.001)。结论:HBOT可改善STZ大鼠糖尿病性周围神经病变,其机制可能与促进NGF、IGF-1、NO合成,抑制MMP-1有关。

Objective： To investigate whether hyperbaric oxygen therapy（HBOT） can improve the peripheral neuropathy in streptozotocin-induced diabetic rats, and to study its possible mechanisms. Method： The diabetic rat model was induced by injection intraperitonally of streptozotocin. Rats were randomly divided into two groups：①HBOT group（n=31）： inhale oxygen（concentration〉97%） in animal chamber lh per day at the pressure of 0.15MPa for 1 to 20 days.②Diabetic control group（DM,n=32）： 32 diabetic rats complicated peripheral neuropathy without any treatment.③Normal group（NC,n=20）. At the 10th and 20th day of oxygenation, the NCV, latency and wave amplitude of tibial nerve and sural nerve of rats right-behind limbs were measured in the three groups using the electromyograph and the arterial blood was collected from bilateral femoral artery and serum levels of IGF, NGF, NO and MMP-1 were measured. Result： Before treatment,the NCV of diabetic rats was slower than normal rats. At 10days after HBOT, the NCV of tibial nerve and sural nerve of the right-behind limbs of treatment group was faster significantly than DM group （P〈0.05）, but they were still slower than normal group. The serum levels of NGF and NO increased slightly but without statistical meaning. At 20 days after oxygenation, NCV of the tibial nerve and sural nerve increased significantly than DM group timely and treatment group 10-days before, but there was no significant difference of the NCV between HBOT group and normal group at this time, The abnormal ultrastructure of DM group was improved in treatment group, like the decreasing of axon,and denaturation and incrassation of myelin, and the number of Schwann cell increased significantly than DM group.The levels of NGF,IGF-1 and NO in HBO group were higher than DM group, and its MMP-1 level decreased significantly compared with DM group and baseline.Conclusion：The hyperbaric oxygen therapy improves the peripheral neuropathy in STZ-diabetic rats, its mechanism may be related to induce the synthesis of NGF,IGF-1 and NO, and inhibiting the MMP-1.