牛磺酸对大鼠肢体缺血再灌注后肺损伤时细胞凋亡的影响

Influence of taurine on apoptosis in acute lung injury following limbs ischemia- reperfusion in rats

目的:从细胞凋亡的角度探讨肢体缺血再灌注(LIR)后急性肺损伤(ALI)的发病机制及牛磺酸的影响。方法:复制大鼠肢体缺血再灌注(LIR)损伤动物模型,采用TUNEL法、电泳法、半定量逆转录聚合酶链反应(SqRT-PCR)及免疫组织化学等技术观察LIR后肺损伤发生过程中,肺泡上皮及血管内皮细胞凋亡变化以及Fas/FasL系统蛋白质和mRNA表达的改变。结果:大鼠LIR后,肺泡上皮细胞和肺血管内皮细胞凋亡明显增加;肺组织Fas/FasL mRNA和蛋白质表达明显上调,DNA断链率、组织钙含量和活性氧(ROS)升高,且与肺泡上皮及血管内皮细胞凋亡的增加相一致。结论:肺泡上皮及血管内皮细胞凋亡以及Fas/FasL系统表达明显上调可能参与LIR后ALI的发生;牛磺酸可减少肺组织细胞凋亡,但并非通过影响Fas/FasL基因表达而实现其保护效应。

AIM: To investingate the potential role of apoptosis in the development of acute lung injury(ALI) following limbs ischemia-reperfusion(LIR) in rats and the effects of raurine. METHODS: The model of LIB injury in rats was made. By using TUNEL, electrophoresis, reverse-transcription polymerase chain reaction(RT-PCR) and immunohistochemistry techniques, pulmonary apoptosis, Fas/FasL expressions and Ca^(2+), reactive oxygen species (ROS),the ratio of DNA double chain in tissue were detected in different groups.RESULTS: The rapid appearance of apoptosis in alveolar epithelial cells and pulmonary vascular endothelial cells were observed after LIR in rats. The ratio of DNA double chain decreased and tissue Ca^(2+) increased. The expression of Fas/FasL mRNA and protein was up-regulated in lung tissue of rats after LIR, which was related to the elevation of alveolar epithelial cells and pulmonary vascular endothelial cell apoptosis. Taurine decreased alveolar epithelial cell and pulmonary vascular endothelial cell apoptosis not by down-regulating expression of Fas/FasL system. CONCLUSIONS: These results suggest that the excessive apoptosis and Fas/FasL system expression may play a role in the pathogensis of ALI following LIB in rats, and taurine decreases alveolar epithelial cell and pulmonary vascular endothelial cell apoptosis.