目的观察脓毒症大鼠血清及肾组织内皮细胞特异性分子1(ESM-1)含量的动态变化并探讨其与肾损害之间的关系。方法雄性SD大鼠36只,按照完全随机分组方法分成6组:①正常对照组(n=6);②假手术组(n=6);③脓毒症组,按时相点再分为3、6、12、24h组(n=6)。采用盲肠结扎穿孔(CLP)法制作大鼠脓毒症模型,假手术组除不结扎、穿孔盲肠外,其余处理同脓毒症组。动态观察各组大鼠血清ESM-1、肌酐(Cr)、尿素氮(BUN)的改变;肾组织石蜡切片HE染色观察肾脏组织学改变;免疫组化定量检测肾组织ESM-1的表达情况。结果与正常对照组比较,脓毒症6h、12h、24h组血清ESM-1均显著升高(P〈0.05,P〈0.01),脓毒症12h组BUN水平显著升高(P〈0.05),脓毒症24h组Cr水平显著升高(P〈0.05)。脓毒症组随时相点的变化肾组织ESM-1表达呈进行性升高(P〈0.01),与脓毒症3h、6h组比较,脓毒症12h、24h组肾组织ESM-1的积分光密度值和平均光密度值显著增高(P〈0.05)。血清ESM-1水平变化与BUN及Cr水平呈正相关(r=0.97,P=0.01;r=0.82,P=0.04)。结论脓毒症大鼠血清ESM-1水平及肾组织ESM-1表达显著增高,且与肾损害密切相关;ESM-1对于早期肾损害的检测敏感性高于常规肾功能指标。
Objective To investigate the dynamic changes in endothelial cell specific molecule-1 (ESM-1) in rat with sepsis and the relationship between ESM-1 level and renal injury. Methods Thirty-six SD rats were randomly divided into six groups: normal control group (n=6), sham operation group (n=6) ; CLP group (n=24), and in the latter group rats were divided into four subgroups according to time after CLP: CLP3h, CLP6h, CLP12h and CLP24h group (6 each). In rats of CLP group cecal ligation and puncture (CLP) was done to produce sepsis, and rats in sham operation group underwent the same surgical procedure as CLP group except the cesum was not ligated and punctured. The changes in ESM-1, blood urea nitrogen (BUN) and creatinine (Cr) level in peripheral blood were determined. Paraffin section and HE staining were used to examine pathological changes in kidney tissue, and immunohistochemisty was used to determine the ESM-1 expression in kidney tissue. Results Compared with normal control group, the serum level of ESM-1 increased signifi cantly in CLP6h, CLP12h and CLP24h group (P〈0. 05 or P〈0. 01), and the serum level of BUN and Cr increased in CLP12h and CLP24h groups (P〈0. 05). ESM1 expression in kidney tissue showed progressive elevation as the time of CLP was prolonged (P〈0. 01). The integrating and average optical density of ESM 1 in kidney tissue were significantly increased in CLP12h and CLP24h groups compared with those in CLP3h and CLP6h groups (P%0. 05). The serum ESM-1 level was positively correlated to BUN and Cr (r=0. 97, P=0. 01;r=0. 82, P=0. 04). Conclusions ESM-1 levels of serum and kidney tissue increase significantly in septic rats, which is closely related to the renal injury, and the detection is more sensitive than the routine clinical parameters of renal function in reflecting the renal pathological process.