中文摘要：

目的探讨阿托伐他汀（ATO）联合低分子肝素（LMWH）对脓毒症大鼠炎症反应及肺脏的保护作用。方法选择健康雄性SD大鼠122只，按随机数字表法分为假手术（Sham）组（n=10）、脓毒症组（n=10）、ATO组（n=34）、LMWH组（n=34）、ATO联合LMWH组（联合组，n=34）。采用盲肠结扎穿孔术（CLP）制备脓毒症大鼠模型；Sham组只开腹，不结扎、穿孔。各预处理组于术前相应灌胃ATO20mg／kg以及皮下注射LMWH100U／kg或二者联用，均连续给药5d。依据改良脓毒症严重程度评定标准对各组大鼠的病情程度进行评分；每组取10只大鼠观察7d存活情况。于术前（0h）及术后4、8、12、24h取血，采用酶联免疫吸附试验（ELISA）检测血浆肿瘤坏死因子-α（TNF—α）、白细胞介素（IL-1β）、高迁移率族蛋白β1（HMGβ1）水平；术后24h取肺组织，苏木素-伊红（HE）染色后光镜下观察病理学改变。结果①脓毒症组术后4h病情严重程度评分即较Sham组明显增高（分：12．2±2．0比7．2±0．5，P〈0．05），且呈逐渐升高趋势，7d累积死亡率达90％（9／10）。ATO组、LMWH组、联合组8h起疴隋严重程度评分均较脓毒症组明显下降（分：12．2±2．0、11．2±2．2、10．0±1．7比16．6±2．5，均P〈0．05），7d累积死亡率分别为60％（6／10）、60％（6／10）、40％（4／10），均较脓毒症组显著降低（均P〈0．05）.②Sham组术后各炎性因子水平无明显变化；其他4组各炎性因子水平均较术前明显升高，TNF—α在4h、IL-1β在8h、HMGBl在24h达峰值。脓毒症组各炎性因子水平均较Sham组显著升高；而ATO组、LMWH组、联合组各炎性因子水平均明显低于脓毒症组[4hTNF—α（ng／L）：668．3±124．6、536．5±118．5、496．5±108．5比783．8±134．7，8hIL-1β（ng／L）：2476．7±137．8、2460．4±171．2、2090．0±151．2比2873．9±295．6，24hHMGB1（μg/L）：654?

英文摘要：

Objective To investigate the influence of combined use of atorvastatin （ATO） and low molecular weight heparin （LMWH） on the inflammatory reaction and pulmonary protection functions in rats with sepsis. Methods A total of 122 healthy male Sprague-Dawley （SD） rats were divided into five groups using a random number table： sham-operated group （sham group, n = 10）, sepsis group＇ （n = 10）, ATO group （n=34）, LMWH group （n = 34）, and ATO combined with LMWH group （ATO＋LMWH group, n = 34）. The rat model of sepsis was reproduced by cecal ligation and puncture （CLP）, while in sham group, rats were only subjected to laparotomy without cecum ligation and puncture. The rats of each pretreatment group received relevant therapies for 5 days, either gastric perfusion with ATO 20 mg/kg or subcutaneous injection with LMWH 100 U/kg or both before operation. The sepsis severities of the model animals were scored according to the modified sepsis severity assessment standards of experimental animals. Ten rats in each group were calculated the 7-day cumulative mortality rate. Blood samples from 6 rats in each group were collected to determine the levels of tumor necrosis factor- α （TNF- α）, interleukin-1β （IL-1 β ） and high mobility group protein box-1 （HMGB1） contents in plasma using enzyme linked immunosorbent assay （ELISA） before operation （0 hour） and 4, 8, 12, and 24 hours post operation. The lung tissue was harvested 24 hours after operation, and the pulmonary pathology was assayed by hematoxylin and eosin （HE） staining using optical microscope. Results ① The sepsis severity grades of sepsis group were significantly higher than those of sham group at 4 hours after operation （score： 12.2 ± 2.0 vs. 7.2 ± 0.5, P 〈 0.05 ）. Furthermore, they displayed a gradually increasing tendency, with the 7-day cumulative mortality rate being 90% （9/10）. The sepsis severity grades in ATO group, LMWH group, and ATO＋LMWH group showed a significant decrease compare