别嘌醇抑制黄嘌呤氧化酶对缺氧和高氧大鼠心率变异性的影响

Effect of xanthine oxidase inhibition by allopurinol on the heart autonomic regulation of hypoxia or hyperoxia rats

目的评估别嘌醇对黄嘌呤氧化酶(XO)的抑制对缺氧和高氧大鼠心率变异性(HRV)的作用。方法 16只Wistar大鼠分为对照组和别嘌醇组,每组8只,别嘌醇组预先注射二甲基亚砜,通过自动可调压力调节器创造低压缺氧或高氧的条件,腹腔注射XO抑制剂别嘌醇(50 mg/kg);而对照组则给予等体积的生理盐水。分析两组HRV的变化。使用2,4-二硝基苯肼(DNPH)比色法测定蛋白质羰基含量,ELISA法测定血浆8-异前列腺素F2α(8-ios-PGF2α)浓度,使用Cayman检测试剂盒对XO、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)进行活性评估。结果与对照组相比,别嘌醇组XO活性显著被抑制,SOD活性显著升高和血浆中8-ios-PGF2α显著降低(P<0.05),然而XO抑制并未导致血浆蛋白羰基的显著变化。在缺氧或高氧情况下,别嘌醇组RR间期标准差(SDNN)、总功率谱(TSP)、低频(LF)、相邻RR间期差的均方根(rMSSD)和高频(HF)较别嘌醇给药前显著增加(P<0.05),自主平衡指标LH/HF和SDNN/rMSSD则没有显著差异。结论别嘌醇可降低意识清醒大鼠缺氧或高氧引起的氧化应激,而在常氧条件下,XO抑制作用可能不干扰神经源性心脏调节。

Objective To evaluate the effect of xanthine oxidase(XO) inhibition by allopurinol on the heart rate variability of rats under hypoxia or hyperoxia.Methods Sixteen Wistar rats were divided into the control group and the allopurinol group, with 8 rats in each group. The allopurinol group was pre-injected with dimethyl sulfoxide, and the conditions of hypobaric hypoxia or hyperoxia were created by an automatically adjustable pressure regulator. The XO inhibitor allopurinol(50 mg/kg) was injected, while the control group was given with equal volume of physiological saline. The changes of HRV before and after injection in the control group and allopurinol group were analyzed. The carbonyl content of the protein was determined by 2,4-dinitrophenylhydrazine(DNPH) colorimetric method. The plasma 8-isoprostane F2α(8-ios-PGF2α) concentration was determined by ELISA. Activity assessment of XO, superoxide dismutase(SOD), glutathione peroxidase(GPx) and catalase(CAT) were performed using the Cayman assay kit. Results Compared with the control group, XO activity was significantly inhibited in the allopurinol group, while SOD activity was significantly increased, and plasma 8-os-PGF2α was significantly decreased(P<0.05). However, XO inhibition did not result in significant changes in plasma protein carbonyl. In the condition of hypoxia or hyperoxia, the SDNN, TSP, LF, rMSSD and HF in allopurinol group were significantly increased compared with before administration of allopurinol(P<0.05). There was no significant difference between the independent balance indicators LH/HF and SDNN/rMSSD. Conclusion Allopurinol can reduce oxidative stress induced by hypoxia or hyperoxia in awake rats, while under normoxic conditions, XO inhibition may not interfere with neurogenic cardiac regulation.