辛伐他汀抑制脓毒症小鼠肠损伤和细胞间粘附分子-1与髓过氧化物酶上调  

Simvastatin inhibits injury and upregulation of intercellular cell adhesion molecule-1 and myeloperoxidase in the intestines of mice with sepsis

作　　者：张荣[1] 孔冰冰 杨文萍 赵欣 王煜[1] Zhang Rong;Kong Bingbing;Yang Wenping;Zhao Xin;Wang Yu(Emergency Dept of Shengjing Hospital of China Medical University,Shenyang 110004,China;Emergency Dept of Beijing Tsinghua Changgung Hospital,Beijing 102200,China;Intensive Care Unit of Central Hospital Affiliated to Shenyang Medical College,Shenyang 110075,China;Emergency Dept of Chifeng Municipal Hospital,Chifeng 024000,China)

机构地区：[1]中国医科大学附属盛京医院急诊科,沈阳110004 [2]北京清华长庚医院急诊科,北京102200 [3]沈阳医学院附属中心医院重症医学科,沈阳110075 [4]赤峰市医院急诊科,赤峰024000

出　　处：《中国组织化学与细胞化学杂志》2018年第5期428-433,共6页Chinese Journal of Histochemistry and Cytochemistry

摘　　要：目的研究腹腔注射辛伐他汀对盲肠穿孔法造模致脓毒症小鼠肠损伤的保护作用。方法 72只雄性C57BL/6小鼠随机分成下列3组(24只/组):假手术组(Sham组)、脓毒症组(SEP组)、脓毒症+辛伐他汀治疗组(SIM组)。应用盲肠结扎穿孔法(CLP)制作脓毒症小鼠模型,Sham组仅开腹,不进行盲肠结扎和穿孔。分别于造模成功后12h、24h将小鼠处死,取其小肠组织,观察小肠组织病理学变化;酶联免疫吸附法(ELISA)测定肠组织匀浆细胞间粘附分子-1(ICAM-1)及髓过氧化物酶(MPO)浓度。结果光镜下可见Sham组小鼠小肠黏膜形态基本正常,造模后12h,24h病理表现无显著差异;SEP组小鼠小肠壁变薄,绒毛水肿,绒毛结构模糊,肠上皮坏死脱落,炎细胞浸润明显,SEP 24h小鼠病变更加明显;SIM组小鼠小肠壁结构有部分破坏,黏膜水肿程度较轻,仅有少量炎细胞浸润,与SEP组相同观察点比小肠组织损伤减轻。与Sham组相比较,SEP组小肠组织匀浆中ICAM-1、MPO明显升高;与SEP组比较,SIM组小肠组织匀浆中ICAM-1、MPO明显降低。结论辛伐他汀对脓毒症小鼠肠损伤起保护作用,其作用可能与抑制中性粒细胞(PMN)聚集、下调ICAM-1水平有关。Objective In this study,simvastatin was administered by intraperitoneal injection to investigate the protective effect of simvastatin on intestinal injury in sepsis mice induced by cecal ligation and puncture.Methods 72 male C57BL/6 mice were randomly divided into the following 3 groups(24/group):sham-operation group(Sham group),sepsis group(SEP group),sepsis+simvastatin therapy group(SIM group).The cecal ligation and puncture method(CLP)was used to construct a mouse model of sepsis.The Sham group only performed laparotomy without cecal ligation and perforation.The mice were sacrificed at 12h and 24h after successfully establishment of the model,Then intestinal tissues were taken to observe the pathological changes of the intestine;and the intercellular cell adhesion molecule-1(ICAM-1)and myeloperoxidase(MPO)concentrations of the intestinal tissue homogenate were determined by enzyme-linked immunosorbent assay(ELISA).Results Under the light microscope,the villi in the small intestine of the Sham group were arranged neatly,the intestinal mucosal morphology was basically normal,and there was no significant difference in the pathological appearance at 12h and 24h after modeling.In the SEP group,thinner intestinal wall,villous edema,fuzzy villi structure,loss and necrosis of intestinal,and significant inflammatory cells infiltration into epithelium were observed,which were more severe in SEP mice at 24h after modeling.The structure of the small intestine wall in the SIM group was partially destroyed,the degree of mucous membrane edema was milder,and only a small amount of inflammatory cells infiltrated,which were less severe compared with the same observation point of SEP group.Compared with Sham group,ICAM-1 and MPO in the small intestine homogenate of SEP group were significantly higher.Compared with SEP group,ICAM-1 and MPO in the small intestine homogenate of SIM group were significantly lower.Conclusion Simvastatin has a protective effect on intestinal injury in septic mice,which may be related to the inhibition

关 键 词：脓毒症 肠损伤 辛伐他汀 细胞间黏附分子-1 髓过氧化物酶 

分 类 号：R365[医药卫生—病理学]