摘要
目的 探讨洛伐他汀对脓毒症急性肺损伤大鼠肺组织硫酸乙酰肝素蛋白聚糖（HSPG）及多配体蛋白聚糖-1（SDC-1）脱落的影响.方法 健康雄性清洁级Wistar大鼠120只,8～12周龄,体重325～ 425 g,采用随机数字表法将大鼠分为3组（n=40）：假手术组（S组）、脓毒症组（CLP组）和洛伐他汀组（L组）.S组和L组腹腔注射洛伐他汀4 mg/kg,连续5d,1次/d,CLP组腹腔注射等容量CMC溶剂.连续给药第5天CLP组和L组采用盲肠结扎穿孔法制备脓毒症模型.术后24 h时,进行支气管肺泡灌,测定支气管肺泡灌洗（BALF）蛋白浓度、白细胞计数和中性粒细胞百分比;取血样,采用ELISA法测定血清HSPG及SDC-1浓度.取肺组织,观察病理学结果,采用PCR法及Western blot法分别测定肺组织HSPG及SDC-1的mRNA及蛋白的表达水平,采用伊文思蓝法检测肺毛细血管通透性.结果 与S组比较,CLP组及L组BALF蛋白浓度、白细胞计数、中性粒细胞百分比及肺组织伊文思蓝含量升高,血清HSPG及SDC-1浓度升高,肺组织HSPG及SDC-1的mRNA及其蛋白表达下调（P＜0.05）;与CLP组比较,L组BALF蛋白浓度、白细胞计数、中性粒细胞百分比及肺组织伊文思蓝含量降低,血清HSPG及SDC-1浓度降低,肺组织HSPG及SDC-1的mRNA及其蛋白表达上调（P＜0.05）.L组肺组织损伤较CLP组减轻.结论 洛伐他汀减轻脓毒症大鼠急性肺损伤的机制可能与减少肺组织HSPG及SDC-1脱落,改善肺血管内皮功能有关.
Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan （HSPG） and syndecan-1 （SDC-1） in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups （n =40 each） using a random number table：sham operation group （group S）,cecal ligation and puncture （CLP） group and lovastatin group （group L）.Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5% CMC （the solvent） was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid （BALF） was collected for determination of protein concentrations,white blood cell （WBC） count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum （by ELISA）.Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression （using Western blot and PCR）,and Evans blue content （reflecting pulmonary capillary permeability） in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2015年第2期222-225,共4页
Chinese Journal of Anesthesiology
基金
南京市医学科技发展项目（201108028,ZKX11028）
