辛伐他汀对脓毒症大鼠肺组织诱导型一氧化氮合酶表达的影响

Effect of Simvastatin on the expression of nitric-oxide synthase in lung tissue of rats with sepsis

目的:探讨辛伐他汀对脓毒症大鼠肺组织诱导型一氧化氮合酶(iNOS)表达的影响。方法:90只健康SD大鼠随机分为对照组(生理盐水2mL静脉滴注)、内毒素(LPS)组(LPS5mg/kg,用生理盐水稀释至2mL静脉滴注)、LPS+辛伐他汀(Sta)组(LPS5mg/kg,Sta20mg/kg,生理盐水稀释至2mL静脉滴注),每组30只。分别在用药后2、4、6、12、24h处死大鼠,取右肺下叶用RT-PCR法检测肺组织iNOSmRNA表达。结果:光镜下对照组各时点肺泡结构正常;LPS组2h出现炎症损伤,以6h最为显著;LPS+Sta组中性粒细胞浸润较LPS组减轻。LPS组iNOSmRNA表达较对照组和LPS+Sta组明显增高(均P<0.05),6h达高峰,12h开始下降;LPS+Sta组各时点iNOSmRNA表达趋势同LPS组,但接近对照组水平(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,辛伐他汀能减低脓毒症时肺组织iNOSmRNA的表达。

Objective： To investigate the effect of simvastatin on the expression of nitric-oxide synthase in lung tissue of rats with sepsis. Methods： Ninety healthy male Sprague-Dawley rats were randomly divided into 3 groups, 30 for each group. All the rats received administration by caudal vein with a capacity volume of 2 mL. Control group was treated with 2mL saline. Lipopolysaccharide （LPS） group was treated with LPS （5mg/kg）, LPS ＋ Sta group was treated with LPS （5mg/kg） plus Simvastatin （20mg/kg）. Six rats in each group were killed at 2, 4, 6, 12 and 24 hours after the injection respectively. Then right middle lobe of lung tissue was taken out for detection of iNOS mRNA by the reverse transcription polymerase chain reaction （RT-PCR）. Results： Microscopic studies showed that there were no pathological changes in the lung tissue of rats in the control group. The alveolar wall was hypercelluar and infiltrated with mononuelear cells and scat- tered polymorphonuclear leukocytes in the LPS group at 2 hours. Furthermore, severe interstitial edema of lung and prolifer- ation of epithelial ceils were observed in the lung tissue of LPS group. In the LPS ＋ Sta group, the degree of the infiltration of leukocytes and the lung interstitial edema were less severe than those in LPS group. Expression of iNOS mRNA was weak in the control group. At all time points, the expression of iNOS mRNA in LPS group was significantly higher than that in control group （P 〈 0.05）. The expression of iNOS mRNA was increased at 2 hours, and reached the peak at 6h, then de- creased at 12 hours. Expression in the LPS ＋ Sta group was significant lower than that in the LPS group at all time points （P 〈 0.05 ） and was similar to that in the control group at all time points （ P 〉 0.05 ）. Conclusions ： Simvastatin could a- meliorate pathological changes of lung in sepsis. Simvastatin could decrease the expression of iNOS mRNA in lung tissue of septic rat.