摘要
目的 探讨辛伐他汀对脂多糖（LPS）致大鼠脓毒症模型肝损害的保护作用及相关机制.方法 将56只雄性SD 大鼠按随机数字表法分为对照组（8只）、模型组（24只）、辛伐他汀组（24只）。腹腔注射 LPS 10 mg/kg 复制脓毒症大鼠模型。对照组和模型组于腹腔注射生理盐水或LPS 前给予生理盐水1 ml/d 灌 胃，辛伐他汀组于制模前给予辛伐他汀20 mg·kg-1·d-1 灌胃，均连续1 周。于制模后6、12、24 h 测定血清丙氨酸 转氨酶（ALT）、天冬氨酸转氨酶（AST）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-6、IL-10）水平及肝脏组织 丙二醛（MDA）含量，并观察24 h 肝脏组织病理学改变. 结果 与对照组比较，模型组和辛伐他汀组各时间点血 清ALT（U/L）、AST（U/L）、TNF-α（ng/L）、IL-6（ng/L）、IL-10（ng/L）及肝组织MDA（nmol/mg）水平均明显升高 （均P ＜0.05）。 模型组制模后12 h ALT、AST 达峰值，制模后6 h TNF-α、IL-6、IL-10、MDA 达峰值，以后有所 下降。辛伐他汀组制模后24 h ALT、AST 较模型组下降更显著（ALT：60.5±8.9 比81.8±13.9，AST：167.9±19.7 比200.9±26.9，均P ＜0.05），制模后6 h TNF-α 较模型组显著降低（105.5±19.5 比154.1±24.1，P ＜0.05），制模 后6 h、12 h IL-6、MDA 较模型组明显下降（6 h IL-6：2910.9±353.6 比3777.8±687.4，12 h IL-6：386.1±48.3 比 475.2±45.9 ； 6 h MDA ：0.60±0.09 比0.73±0.12，12 h MDA ：0.49±0.09 比0.60±0.12，均P ＜0.05），IL-10 较模 型组显著升高（6 h：2090.6±262.5 比1690.6±187.0，12 h：548.9±45.4 比496.9±45.2，均P ＜0.05）；24 h 肝组织 病理学改变较模型组明显改善. 结论 辛伐他汀通过抗炎及减轻氧化应激反应对LPS 诱导的脓毒症大鼠肝 脏具有保护作用.
Objective To study the protective effects of simvastatin on liver injury and its associated mechanism in rats with lipopolysaccharide （LPS） -induced sepsis. Methods Fifty-six male Sprague-Dawley （SD） rats were randomly divided into three groups ： control group （n = 8）, model group （n =24） and simvastatin treated group （n =24）.The septic model was set up by receiving LPS 10 mg/kg intra-peritoneal injection. The control group and model group were consecutively given saline 1 ml/d intra-gastrically for one week before intra-peritoneal injection of saline or LPS respectively. Simvastatin treated group was given simvastatin 20 mg·kg^-· d ^-1 intra-gastrically for one week, The levels of serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, tumor necrosis factor（TNF- α ）, interleukin （IL-6, IL-10） and liver malondialdehyde （MDA） content were detected after intra-peritoneal injection for 6, 12 and 24 hours. Pathological changes of liver were examined at 24 hours. Results Compared with the control group, serum ALT （U/L）, AST （U/L）, TNF-α （ug/L）, IL-6 （ng/L）, IL-10 （ng/L）levels and liver MDA （nmol/mg） content increased significantly in model group and simvastatin treated group （all P〈0.05） at various time points. Serum ALT and AST peaked at 12 hours, serum TNF-α, IL-6, IL-10 and liver MDA peaked at 6 hours, and then they were decreased in the model group. Compared with model group, in simvastatin treated group, the serum ALT and AST were decreased more obviously at 24 hours （ALT ： 60.5±8.9 vs. 81.8±13.9, AST ： 167.9±19.7 vs. 200.9±26.9, both P〈0.05）, serum TNF-α was reduced significantly at 6 hours （ 105.5±19.5 vs. 154.1±24.1, P〈 0.05）, serum IL-6 and liver MDA were reduced obviously at 6 hours and 12 hours （6 hours IL-6 ： 2910.9±353.6 vs. 3777.8±687.4, 12 hours IL-6 ： 386.1±48.3 vs. 475.2±45.9 ;6 hours MDA ：0.60±0.09 vs. 0.73±0.12, 12 hours MDA ： 0.49±0.09 vs. 0.60±0.12, all P〈0.05）, serum IL-10 was increased markedly at 6 hours and 12 hours （6 hours ： 2090.6±262.5 vs. 1690.6± 187.0, 12 hours ： 548.9±45.4 vs. 496.9±45.2, both P〈0.05）. The pathological examination of simvastatin treated group showed the damage of liver tissue was improved remarkably compared with that of model group at 24 hours. Conclusions Simvastatin can protect liver injury induced by LPS. This effect may be related to attenuating inflammatory reaction and decreasing oxidative stress level.
出处
《中国中西医结合急救杂志》
CAS
北大核心
2012年第5期283-286,共4页
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
基金
基金项目：广州市医药卫生科技重点项目（2008-ZDi-16）
