人硫氧还蛋白对大鼠肺缺血再灌注损伤的保护作用及机制

目的探讨人硫氧还蛋白（hTrx）对肺缺血再灌注（I/R）损伤的保护作用及可能机制。方法将健康清洁级Wistar大鼠84只随机分为对照组12只、I/R组和Trx组各36只,后两组复制I/R肺损伤模型,Trx组于缺血前10 min和再灌注前10 min腹腔注射重组hTrx注射液0.75 mg/kg。于再灌注1、3、5 h分别取三组肺组织检测超氧化物歧化酶（SOD）活性,丙二醛（MDA）含量;原位缺口末端标记（TUNEL）法测定细胞凋亡指数（AI）;原位杂交法检测Caspase-3 mRNA表达。结果 I/R组各时点MDA含量、细胞AI和Caspase-3 mRNA表达均显著高于对照组（P均〈0.01）,而SOD活性则随再灌注时间延长有所降低;Trx组MDA含量、AI、Caspase-3 mRNA表达均显著低于I/R组（P均〈0.01）。AI与MDA、Caspase-3 mRNA呈显著正相关（r分别为0.844,0.775,P均〈0.01）;与SOD呈显著负相关（r为-0.820,P〈0.01）。结论 Trx对I/R后肺组织细胞凋亡具有抑制作用;其机制可能与清除自由基、抑制脂质过氧化、下调Caspase-3 mRNA表达有关。

Protective effects and mechanism of human thioredoxin on lung ischemia reperfusion injury in rats

Objective To investigate the protective effects of human thioredoxin（hTrx） on lung ischemia/reperfusion（I/R） injury in rats and probable mechanism.Methods Eighty-four Wistar rats were randomly divided into control group（n=12）,I/R group and Trx group with 36 in each.The later two groups were prepared I/R lung injury model,Trx group was given intraperitoneal injection of reorganized hTrx 0.75 mg/kg 10 mins before ischemia and reperfusion respectively.The lung tissue of three groups were taken to measure the contents of superoxide dismutase（SOD） and malondialdehyde（MDA）1,3,5 h after the reperfusion;TUNEL was used to observe detect apoptosis index（AI）,and in situ hybridization（ISH） techniques was used to examine the Caspase-3 mRNA expression.Results The content of MDA,AI and the expression of Caspase-3 mRNA at every time point in the I/R group were all significantly higher than those in the control group（all P0.01）,while the activity of SOD gradually increased with the time of reperfusion prolonging;the content of MDA,AI and the expression of Caspase-3 mRNA in the Trx group were all significantly lower than those in the I/R group（P all 0.01）.The AI was positively correlated with the content of MDA and the expression of Caspase-3 mRNA（r=0.844,0.775,respectively;both P0.01）,and negatively correlated with the SOD（r=-0.820,P0.05）.Conclusions Trx can inhibit the apoptosis of lung tissues after the I/R;the mechanism may correlated with the cleaning of free radical suppressing oxidative stress reaction,down-regulating the expression of Caspase-3 mRNA.