辛伐他汀对脓毒症大鼠肺组织核转录因子-κB表达的影响

Effects of Simvastatin on Expression of NF-κB in Lung Tissue of Septic Rats

目的探讨辛伐他汀对脓毒症大鼠肺组织不同时间点的核转录因子κB(NF-κB)蛋白表达的影响。方法 90只SD大鼠随机分为空白对照组(生理盐水2 mL)、内毒素组(脂多糖5 mg/kg,用生理盐水稀释至2 mL)、辛伐他汀组(脂多糖5 mg/kg,辛伐他汀20 mg/kg,生理盐水稀释至2 mL),每组30只,给药途径均通过鼠尾静脉注射。分别在用药后2、4、6、12 h随机快速处死6只大鼠,用免疫法检测肺组织NF-κB表达。结果大鼠肺组织HE染色所见:对照组各时点肺泡结构正常;内毒素组2 h开始出现炎症损伤,以6 h最为显著;辛伐他汀组中性粒细胞细胞浸润较内毒素组减轻。大鼠肺组织不同时间点NF-κB的表达:对照组各时间点NF-κB微量表达;内毒素组各时间点NF-κB较对照组明显增高(P<0.05),6 h达到峰值,12 h开始下降;辛伐他汀组各时间点NF-κB的表达与内毒素组比较差异有统计学意义(P<0.05)。结论辛伐他汀能改善脓毒症时肺组织的病理性炎症损伤,与其抑制NF-κB的表达有关。

Objective To investigate the effects of simvastatin on lung tissue in septic rats by observing the protein expression of nuclear factor kappa B （NF-κB） and pathologic changes in lung tissue at different time points. Methods 90 healthy male Sprague-Dawley rats were randomly divided into three groups （n = 30 in each group）. All the rats received administration by caudal vein and capacity volume is 2 mL. The rats in the control group were treated with saline （2 mL）. The rats in the LPS group were treated with LPS （5 mg/kg ）. The rats in the simvastatin group were treated with LPS （5 mg/kg） and simvastatin （20 mg/kg）. Six rats in each group were killed randomly at 2,4,6, and 12 hours after the injection, and the right middle lobe of lung was taken out. Pathological changes of lung tissue were investigated under light microscope. The expression of NF-κB in lung tissue was determined by immunohistochemistry （IHC） method. Results Microscopic studies showed that there were not pathological changes in the lung tissue of rats in the control group. While in the LPS group, the alveolar spaces were narrowed and the alveolar wall were thickened. Furthermore, severe interstitial edema of lung and proliferation of epithelial cells were observed. In the simvastatin group, the degree of the infiltration of leukocytes and the lung interstitial edema were less severe than those in the simvastatin group. In the control group, the expression of NF-κB protein in most of lung tissue was negative. In the LPS group, the expression of NF-κB protein was detected at 2h, and reached the peak at 6h, then decreased at 12h. In the Simvastatin group, the NF-κB expression was significantly lower than that in the LPS group at all time points （P 〈 0. 01）. Conclusion Simvastatin can ameliorate pathological lesions and decrease expression of NF-κB in lung tissue of septic rats.