贝科能对心肺复苏后大鼠心肌低氧诱导因子-1_α表达的影响

摘要

目的 研究贝科能(复合辅酶)对心肺复苏后大鼠心肌细胞低氧诱导因子1_α(hypoxia-inducible factor 1_α,HIF-1_α)蛋白表达影响及其对心脏损伤的保护作用.方法 实验在第二军医大学附属长征医院急救科实验室完成.SD大鼠72只,随机(随机数字法)分为3组:空白对照组、常规复苏组(包括0.5,2,4,6 h组)和贝科能治疗组(0.5,2,4,6 h组).采用窒息合并冰氯化钾(0.5 mol/L)停跳液致大鼠心跳骤停5 min后开始心肺复苏的动物模型,贝科能治疗组于心跳恢复时给予贝科能(按1支/10 kg)生理盐水稀释至0.3 mL后腹腔注入.采用Western blotting法测定各组大鼠心肌细胞低氧诱导因子1_α蛋白的表达;采用比色法测定心肌丙二醛(MDA)含量及超氧化物歧化酶(SOD)、Na~+-K~+-ATP酶活力.所得数据以均数±标准差(~(-)x±s)表示,多组间比较采用单因素方差分析,两组间比较采用q检验.结果 与对照组相比,常规复苏组各时间点HIF-1_α蛋白的表达均有增强(P＜0.05),2 h最高(空白对照组0.15±0.02,常规复苏组组0.57±0.06),MDA含量显著升高(P＜0.05),而SOD及Na~+-K~+-ATPase活力显著降低(P＜0.05).与常规复苏组相比,贝科能组各时间点心肌细胞HIF-1_α蛋白表达均减少(P＜0.05),其中2 h组差异最为显著[贝科能组(0.29±0.03),常规复苏组(0.57±0.06)];心肌MDA含量明显降低(P＜0.05),SOD及Na~+-K~+-ATP酶活力明显升高(P＜0.05).结论 HIF-1_α蛋白在心肺复苏后大鼠心肌细胞的表达增强;贝科能在提高Na~+-K~+-ATP酶活性的同时,下调HIF-1_α蛋白在心肌细胞的表达.贝科能可能是通过减轻缺血-再灌注损伤,对CPR后大鼠心肌细胞起到保护作用的.%Objective To investigate the effects of Biocoen on HIF-la expression in myocardium and protection from cardiac injury in SD rats after cardiopulmonary resuscitation(CPR).Method Seventy-two male SD rats were randomly(random number)divided into three groups:sham control group,routine treatment group (0.5,2,4 and 6 h subgroups)and Biocoen intervention group(0.5,2,4 and 6 h subgroups).Cardiac arrest was induced by sueeinylcholine to render rats asphyxiated along with ice-cold 0.5 moL/L KCI injection,and resuscitation was initiated in five minutes.In Biocoen intervention subgroups diluted Bioeoen was intraperitoneally injected when their heartbeats resumed.The Western blotting method was used to assay HIF-1α_ protein in eardiomyoeytes in all groups.The eolorimetry was used to determine the quantity of malondialdehyde(MDA)and activity of superoxide dismutase(SOD),and Na~+-K~+-ATPase in cardiomyocytes.One-way ANOVA was used for comparison among multiple groups,and SNK-q test was used for comparison between two groups.Results Compared with the sham group,HW-1_α protein in routine CPR groups was significantly increased(P＜0.05)and peaked at 2 hours after ROSC(0.15±0.02 in sham group)in routine group(0.57±0.06),and the quantity of MDA significantly increased(P＜0.05)along with notably declined activity of SOD and Na~+-K~+-ATPase(P＜0.05).Compared with the routine CPR groups,HIF-1_α protein in all Biocoen groups were decreased(P＜0.05)with the most significant differences between these two-hour groups[(0.29±O.03)in Biocoen intervention group vs.(0.57±0.06)in routine CPR group]along with notably increased activity of SOD and Na+-K+-ATPase (P＜0.05).Conclusions HIF-1α protein enhanced in myocardium cells of rats after CPR.Biocoen can enhance Na~+-K~+-ATPase activity and reduce the level of HIF-1_α protein in myocardial cells.Meanwhile,Bioccen can lessen the injury of myocardial cells caused by ischemia-repetfusion injury,and plays a pivotal role in protection of the heart after CPR.