辛伐他汀对脂多糖诱导肺损伤大鼠的一氧化氮合酶的影响

目的 探讨辛伐他汀对脂多糖(LPS)诱导急性肺损伤大鼠的一氧化氮合酶(NOS)的影响.方法 30只SD大鼠随机分为对照组、LPS组和辛伐他汀治疗组,治疗组又分1 h、3 d和7 d组,每组6只.治疗组大鼠在实验前经胃管分别给予辛伐他汀10 mg/kg(4 ml/kg)治疗1 d,3 d,7 d,每天1次;对照组和LPS组则给予蒸馏水(4 ml/kg),每天1次,连续7 d.在最后一次给药1 h后,LPS组和治疗组大鼠从尾静脉注射LPS 5 mg/kg(2.5 ml/kg),对照组则予注射无菌生理盐水(2.5 ml/kg).观察6 h,处死大鼠,取样,比色法测定血清和肺匀浆诱导型一氧化氮合酶(iNOS)、构成型一氧化氮合酶(cNOS)和一氧化氮(NO)水平,免疫组化法检测肺组织iNOS和内皮型一氧化氮合酶(eNOS)的表达.结果 LPS组血清和肺匀浆NO均高于对照组(p<0.001),治疗组则低于LPS组(P<0.05);LPS组血清和肺匀浆iNOS活力均高于对照组而cNOS活力则降低(P<0.05),治疗组肺匀浆iNOS活力显著低于LPS组而eNOS显著升高(P<0.001);免疫组化显示:LPS组肺组织iNOS表达强于对照组,而eNOS表达则显著减弱,治疗组的iNOS表达弱于LPS组,eNOS表达则显著增强,与其减轻肺损伤相关.结论 辛伐他汀可逆转LPS诱导的肺组织iNOS活性的升高和eNOS活性的下降,减轻内毒素性肺损伤.

Effect of simvastatin on nitric oxide synthase in rat lung injury induced by lipopolysaccharide

Objective To investigate the effect of simvastatin on nitric oxide synthase（NOS）in the rat model of lung injury induced by lipopolysaccharide（LPS）.Methods The SD rats were randomly allocated to normal control group and LPS group or simvastatin group,and the simvastatin group were divided to three time-groups（1 h,3 d and 7 d）.The rats in simvastatin groups were pretreated with simvastatin（10 mg·kg-1·d-1,that was 4 ml·kg-1·d-1）for 1 day or 3 days or 7 days via an orogastric tube that was inserted each day,the last dose was given 1 hour before the experiment.The rats in control group and LPS group were pretreated with distilled water via the same way for 7 days.Each animal in the LPS group and simvastatin groups were administered intravenous LPS（5 mg/kg）,the rats in the control group were administered intravenous sterile normal sodium（2.5 ml/kg）.They were sacrificed and taken of samples after the following 6 hours.Measurement of serum and lung homogenate NOS and nitric oxide（NO）were performed by chromometry,and the expression of iNOS and eNOS in the lung tissue were assessed by immunohistochemistry method.Results The serum and lung homogenate NO activity in LPS group were significantly higher than the control group（P〈0.001）,and they were lower in simvastatin groups than the LPS group（P〈0.05）.Compared with the control group,the serum and lung homogenate iNOS activity were significantly higher in LPS group and cNOS activity were lower（P〈0.05）.Compared with the LPS groups,the lung homogenate iNOS activity was significantly lower in all simvastatin groups and cNOS activity was higher（P〈0.001）.Immunohistochemistry showed that,compared with normal group,the expression of iNOS was enhanced significantly and eNOS was attenuated in the LPS group.In contrast,compared with the LPS group,the expression of iNOS was attenuate significantly and eNOS was enhanced in simvastatin pretreated rats.It was related to simvastatin pretreated reduced lung injury.Conclusions Simvastatin can reversal the enhance of lung tissue iNOS activity and the decreases of eNOS,and reduce LPS-induced lung injury in rat.