辛伐他汀对大鼠烟雾吸入性肺损伤中炎症反应的抑制作用

摘要

Objective To explore the protective effects of simvastatin on inhalation lung injury by the mean of restraining the inflammation reaction in rats.Methods 18 healthy standard SD rats were divided into 3 groups randomly,which were normal group,saline group,simvastatin group,with 6 rats in each group.Simvastatin solution (50 mg/kg) was given to the rats in simvastatin group via anorogastric route at 30 rmin and 12 h after the establishment of the model.Rats in saline group were given equal volume of normal saline and the rats in normal group were fed normally.The rats were given intra-peritoneal injection of anesthesia 24 h later.The pathological examination was performed on the right lung and the pathological changes of the lung were scored.The whole arterial blood was centrifuged to take the upper serum.The bronchoalveolar lavage fluid (BALF) was collected from the left lung and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and BALF were measured by ELISA.The expression of nuclear factor-κB p65 (NF-κB p65) in cytoplasm,IL-6 and TNF-α of protein extraction was detected by Western blot in the lung tissue of right lower lung.Results Under microscope observation shows,the alveolar structure of normal group was normal,the alveolar septal edema and the neutrophil infiltration in alveolar cavity in saline group were observed.Compared with saline group,the above symptoms were reduced and the pathological score of lung tissue was decreased in simvastatin group (P ＜ 0.05).The levels of IL-6 and TNF-α both in BALF and serum of saline group and simvastatin group were significantly higher than those in normal group(P ＜ 0.05).Compared with saline group,the levels of IL-6 and TNF-α in BALF and serum in simvastatin group were decreased(P ＜0.05).Same results were emerged in the detection of IL-6,TNF-α and NF-κB p65 in the extraction of the proteins of lung tissue.Conclusion Simvastatin plays a beneficial role in smoke inhalation injury by the mean of inhibiting the production of inflammatory mediators and the infiltration of inflammatory cells and restraining the inflammation reaction to some extent.%目的 研究辛伐他汀对大鼠烟雾吸手性肺损伤中炎症反应的抑制作用.方法 将18只SD大鼠(雌雄不限)随机分为正常组、盐水组、辛伐他汀组,建立烟雾吸手性肺损伤模型,模型建立后30 min及12 h,辛伐他汀组给予辛伐他汀溶液50 mg/kg灌胃,盐水组大鼠给予等量生理盐水灌胃,正常组大鼠正常饲养.于致伤后24 h取右上肺肺组织行病理检查并行病理学评分.经腹主动脉取全血离心留取上层血清,并行左侧支气管肺泡灌洗留取肺泡灌洗液(BALF),采用ELISA法检测血清及BALF中白介素(IL)-6、肿瘤坏死因子(TNF)-α的含量.取右下肺部分肺组织以Western blot法检测蛋白提取物中IL-6、TNF-α及胞质中NF-κB p65的蛋白表达情况.结果 光镜下观察正常组肺泡结构正常,盐水组肺泡间隔水肿,肺泡腔内可见大量的中性粒细胞浸润,而与盐水组相比,辛伐他汀组上述症状减轻且肺组织病理学评分降低(P＜0.05).盐水组、辛伐他汀组血清和BALF中IL-6、TNF-α的含量以及肺组织蛋白提取物中IL-6、TNF-α和NF-κB的表达均较正常组明显升高(P＜0.05).而与盐水组相比,辛伐他汀组大鼠血清和BALF中IL-6、TNF-α的含量以及肺组织蛋白提取物中IL-6、TNF-α及NF-κB p65的表达均降低(P＜0.05).结论 辛伐他汀通过抑制炎症介质的产生及炎症细胞的浸润,减轻吸手性肺损伤的炎症反应,对肺组织起到了一定的保护作用.