PDTC对大鼠急性肺血栓栓塞症溶栓后再灌注损伤的保护性研究  

Protective Effects of PDTC on Reperfusion Injury after Thrombolysis in Rats with Acute Pulmonary Thromboembolism

作　　者：刘玉荣[1] 苏远[1] 张凌[2] 白明[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院呼吸内科,武汉430022 [2]华中科技大学同济医学院附属协和医院心外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2009年第5期585-589,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2004ABA199)

摘　　要：目的探讨抗氧化剂二硫代氨基甲酸吡咯啉烷(PDTC)对大鼠急性肺血栓栓塞症溶栓后肺损伤的干预作用。方法健康雄性SD大鼠72只,随机分为空白对照组、肺血栓栓塞(PTE)组、溶栓组、溶栓+PDTC组(简称PDTC组)。按组再分为栓塞术后或溶栓术后1、24、h观测组,每组6只。建立大鼠急性肺血栓栓塞症模型即PTE模型。采用苏木精-伊红染色观测肺组织病理形态,原位缺口末端标记(TUNEL)法检测肺组织细胞凋亡率,Western印迹法检测Caspase-3蛋白含量,采用黄嘌呤氧化酶法检测血浆超氧化物歧化酶(SOD)活性,硫代巴比妥酸法检测丙二醛(MDA)含量。结果PDTC能有效减轻急性肺血栓栓塞溶栓治疗后肺组织细胞凋亡和再灌注损伤,尤以溶栓后2 h明显。溶栓后2 h,PDTC组Caspase-3蛋白吸光度比值为(0.166±0.005),显著低于溶栓组同时间的吸光度比值(0.228±0.005)(P<0.01);PDTC组肺组织的细胞凋亡率为(24.67±1.21)%,显著低于溶栓组同时间的细胞凋亡率(41.17±2.32)%;PDTC组血浆SOD活性为(69.25±1.64)U/ml,显著高于溶栓组同时间的SOD活性(49.19±1.19)U/ml,PDTC组血浆MDA含量为(3.68±0.13)nmol/ml,显著低于溶栓组同时间血浆MDA含量(5.20±0.14)nmol/ml(均P<0.01)。结论PDTC可能通过提高血浆SOD活性,降低MDA含量,下调Caspase-3蛋白表达,从而抑制溶栓后肺组织细胞异常凋亡,减轻急性肺栓塞溶栓后肺组织的损伤。Objective To explore the protective effect and mechanism of pyrrolidine-dithiocarbamate（PDTC）on reperfusion injury after thrombolysis in rats with acute pulmonary thromboembolism（PTE）.Methods Seventy-two healthy male SD rats were randomly divided into four groups：blank group,PTE model group,thrombolysis group,PDTC group,and each group into 3 subgroups at 1st,2nd,and 4th h after PTE or thrombolysis.The rat PTE model was established by intravenous injection of autologous blood clots.The pathological changes of lung were examined under a light microscope.TUNEL was used to detect the lung cell apoptosis after thrombolysis.By using Western blot,the expression level of Caspase-3 protein was examined.The levels of SOD and MDA were determined by colorimetric method.Results PDTC could effectively alleviate lung cell apoptosis and reperfusion injury after thrombolysis in rats with acute pulmonary thromboembolism especially at 2nd h after thrombolysis.At that time,the level of Caspase-3 protein（0.166±0.005）and the cell apoptosis rate of lung[（24.67±1.21）%] in the PDTC group were significantly lower than those [（0.228±0.005）and（41.17±2.32）%] in thrombolysis group（both P〈0.01）;the level of MDA[（3.68±0.13） nmol/ml]in the PDTC group was significantly lower in thrombolysis group[（5.2±0.14） nmol/ml,P〈0.01];the activity of SOD[（69.25±1.64 U/ml]in the PDTC group was significantly higher than in thrombolysis group[（49.19±1.19） U/ml]at the same time（P〈0.01）.Conclusion PDTC protects the lung after thrombolysis from apoptosis by suppressing the oxidant stress and inhibiting the activation of Caspase-3.

关 键 词：二硫代氨基甲酸吡咯啉烷 急性肺血栓栓塞症 血栓溶解疗法 缺血再灌注损伤 

分 类 号：R563.5[医药卫生—呼吸系统]