七叶皂苷钠对肠缺血再灌注肺损伤大鼠细胞凋亡相关基因的影响

Effects of Sodium Aescinate on the Apoptosis-related Genes in Lung Injury Induced by Intestinal Ischemia Reperfusion in Rats

目的探讨细胞凋亡相关基因与肠缺血再灌注肺损伤的关系及七叶皂苷钠对其的影响,并探讨其作用机制。方法采用夹闭肠系膜上动脉方法复制大鼠肠缺血再灌注损伤模型。实验分为3组(n=8):对照组(Sham组)、肠缺血再灌注组(I/R组)、七叶皂苷钠组(SA+I/R组)。比较各组大鼠肺组织湿/干(W/D)比、肺系数以及血浆和肺组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量的变化;同时免疫组化法检测各组肺组织中Bcl-2和Bax蛋白的表达水平。结果与Sham组相比,I/R组肺组织W/D、肺系数以及血浆和肺组织中MDA含量升高,而SOD活性降低;同时肺组织Bcl-2和Bax的蛋白表达明显增强,且Bax的增强比Bcl-2的增强更为明显,Bcl-2/Bax比值降低;与I/R组比较,SA+I/R组肺组织W/D、肺系数以及血浆和肺组织中MDA含量降低,而SOD活性升高;同时肺组织Bax蛋白表达下降,Bcl-2蛋白表达升高,Bcl-2/Bax比值明显升高。结论肠缺血再灌注肺损伤的发生可能与氧化损伤所致的凋亡调控基因Bcl-2和Bax的蛋白表达异常密切相关,七叶皂苷钠可通过抑制过氧化损伤,上调抑凋亡基因Bcl-2的表达,提高Bcl-2/Bax比值来抑制细胞凋亡,从而减轻肠缺血再灌注肺损伤。

Objective To investigate the relationship between apoptosis-related genes and lung injury induced by intestinal ischemia reperfusion and to explore the effects and its possible mechanism of sodium aescinate.Methods Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery for 60 min and then clamping was relieved for 60 min.Twenty-four SD rats were randomly divided into three groups with eight rats in each： sham group,intestinal ischemia/reperfusion group（I/R group） and sodium aescinate group（SA＋I/R group）.Lung wet/dry weight ratio,lung coefficient and Superoxide dismutase（SOD）,malondialdehyde（MDA） in plasma and lung tissue were measured,as well as the expression levels of Bcl-2 and Bax proteins in lung tissue were examined using immunohistochemical method.Results Compared with sham group,lung wet/dry weight ratio,lung coefficient and MDA in plasma and lung tissue were significantly increased,and while the activity of SOD in plasma and lung tissue were decreased significantly in I/R group.At the same time,the protein expression level of Bcl-2 and Bax were significantly increased.But Bax protein expression was much greater than that of Bcl-2,the ratio of Bcl-2 to Bax was decreased significantly in I/R group than that in sham group.Compared with I/R group,lung wet/dry weight ratio,lung coefficient and MDA in plasma and lung tissue were significantly decreased,and while the activity of SOD in serum and lung tissue were significantly increased in SA＋I/R group. At the same time,Bax protein expression was significantly decreased,both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SA＋I/R group than that in I/R group.Conclusion Lung injury induced by intestinal ischemia reperfusion is correlated with abnormal expression levels of Bcl-2 and Bax protein which is caused by oxidative injury.Sodium aescinate can protect the lung injury induced by intestinal ischemia/reperfusion（I/R）,which may be mediated by inhibiting lipid peroxidation,upregulating Bcl-2 gene protein expression,improving the ratio of Bcl-2/ Bax to inhibit lung apoptosis.