姜晓东^1,2,,
陈杰¹,
宫丹丹^1,3,
于健^1,,
1. 大连医科大学附属第二医院 重症医学科，辽宁 大连 116027
2. 中国医科大学附属第一医院 重症医学科，辽宁 沈阳 110001
3. 大连市中心医院 冠心病三科，辽宁 大连 116033

基金项目: 大连医科大学附属第二医院临床技术水平提升项目（2022LCJSGC11）；大连医科大学附属第二医院院内培育项目（dy2yynpy202204）


详细信息 作者简介: 姜晓东（1981-），男，副主任医师。E-mail：jiangxiaodong@live.cn




通讯作者: 于 健，教授。E-mail：yujian0427@163.com 中图分类号: R365


摘要:目的通过观察西维来司他钠对肝组织炎症因子及肝损伤指标的影响，探讨其对脓毒症急性肝损伤的保护作用。方法60只SPF级雄性C57小鼠随机分为4组，每组15只。假手术（Sham）组：只进行开腹缝合手术，不进行盲肠结扎；假手术+西维来司他钠（Sham+S）组：假手术后腹腔注射100 mg/kg注射用西维来司他钠溶液；脓毒症（CLP）组：盲肠结扎法造模后腹腔注射100 mg/kg生理盐水；脓毒症+西维来司他钠（CLP+S）组：盲肠结扎法造模后腹腔注射100 mg/kg注射用西维来司他钠溶液。观察各组小鼠手术后的状态及活动情况，术后3、6、18小时检测血清中天门冬氨酸氨基转氨酶（AST）、谷氨酸氨基转移酶（ALT）的水平；ELISA法检测肝组织匀浆肿瘤坏死因子α（TNF-α）、白介素-6（IL-6）、中性粒细胞弹性蛋白酶（NE）的水平；肝脏组织HE染色观察病理变化。结果与同时间点Sham组比较，CLP组血清AST、ALT的水平均显著升高（P＜0.05），肝组织匀浆中TNF-α、IL-6、NE的水平显著增高（P＜0.05）；与同时间点CLP组比较，CLP+S组血清AST、ALT的水平均显著降低（P＜0.05），肝组织匀浆中TNF-α、IL-6、NE的水平显著降低（P＜0.05）。Sham组肝组织出现较少的炎症细胞浸润。CLP组肝组织周围布满炎症细胞，血液瘀滞，肝细胞肿胀，排列紊乱，且随着时间的进展，损伤程度逐渐加重。CLP+S组肝组织周围浸润的炎症细胞较CLP组减少，与同时间点CLP组相比，损伤程度有所减轻。结论西维来司他钠可以通过抑制NE及炎症因子TNF-α、IL-6的表达，改善脓毒症所致急性肝损伤，起到保护肝脏的作用。
关键词: 脓毒症/
急性肝损伤/
西维来司他钠/
中性粒细胞弹性蛋白酶/
炎症因子


Abstract:ObjectiveTo investigate the protective effect of sivelestat on liver of mice with sepsis acute liver injury.MethodsSixty SPF male C57 mice were randomly and equally divided into 4 groups. In sham operation (Sham) group, mice were intraperitoneally injected normal saline after sham operation (open suture operation, without caecal ligation). In sham operation+sivelestat (Sham+S) group, mice were intraperitoneally injected sivelestat after sham operation. In sepsis (CLP) group, mice were intraperitoneally injected normal saline after caecal ligation. In sepsis+sivelestat (CLP+S) group, mice were intraperitoneally injected sivelestat after cecal ligation. The status and activities of mice in each group were observed after operation. The contents of aspartate aminotransferase (AST) and glutamate aminotransferase (ALT) in serum at 3, 6 and 18 hours after operation were detected by automatic biochemical analyzer. The levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and neutrophil elastase (NE) in liver tissue homogenates were determined by ELISA. Liver HE staining was performed to observe histopathological changes.ResultsCompared with Sham group at the same time point, the levels of serum AST and ALT in CLP Group were significantly higher (P＜0.05), and the levels of TNF-α, IL-6 and NE in liver homogenate were increased significantly (P＜0.05). Compared with CLP Group at the same time point, the levels of serum AST and ALT in CLP+S group were significantly lower (P＜0.05), and the levels of TNF-α, IL-6 and NE in liver homogenate decreased significantly (P＜0.05). There was less inflammatory cells infiltration in the liver tissue of sham group. In CLP Group, the liver tissue was surrounded by inflammatory cells and red cells. Liver cells were swelling and slightly disordered arrangement and the injury degree was gradually aggravated with the progress of time. Compared with CLP Group at the same time point, the liver injury and inflammatory cells infiltration were less in CLP+S group.ConclusionSivelestat would reduce the liver injury by inhibiting inflammatory factors, such as TNF-α IL-6 and NE in sepsis acute injury mice.
Keywords:sepsis/
acute liver injury/
sivelestat/
neutrophil elastase/
inflammatory factor

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