川芎嗪对脓毒症小鼠肝组织铁调素的表达调控及机制研究  

Ligustrazine regulates expression of hepcidin in septic mice and its mechanism

作　　者：张益维[1] 王珏[1] 朱浩[1] 黄长顺[1] 杨秋红[1] ZHANG Yiwei;WANG Jue;ZHU Hao;HUANG Changshun;YANG Qiuhong(Department of Anesthesiology,Ningbo First Hospital,Ningbo 315000,China)

机构地区：[1]宁波市第一医院麻醉科,315000

出　　处：《浙江医学》2021年第21期2311-2315,共5页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2018KY668);浙江省中医药科技计划项目(2020ZA103)。

摘　　要：目的探讨川芎嗪对脓毒症小鼠肝组织铁调素的表达调控及保护机制研究。方法将44只C57BL/6J雄性小鼠按随机数字表法分为假手术组、肠穿孔手术(CLP)组、CLP+铁调素抑制剂组和CLP+川芎嗪组,每组各11只。后3组小鼠开腹、结扎并穿刺盲肠制作CLP模型。术后12 h取1只CLP组小鼠检测血液载菌量和腹腔液载菌量评估造模情况;观察4组小鼠术后4 d生存率,采用ELISA法检测血清生化指标和炎症因子水平情况,采用Western blot法检测肝组织中铁调素和磷酸化JAK/STAT(p-JAK/STAT)蛋白的表达。结果假手术组小鼠术后12 h在血液和腹腔液中均未检测到细菌。CLP组小鼠模型建立评价结果显示,术后12 h血液和腹腔液载菌量分别为(15.0±1.3)×10^(3)/ml和(8.6±1.0)×10^(3) CFU/ml。假手术组小鼠术后4 d内无死亡,CLP+铁调素抑制剂组和CLP+川芎嗪组小鼠CLP术后4 d生存率分别为75.0%(6/8)和87.5%(7/8),高于CLP组0.0%(0/8),差异均有统计学意义(均P<0.01)。CLP+铁调素抑制剂组与CLP+川芎嗪组小鼠术后48 h血清ALT、AST、TNF-α、IL-1、IL-6和铁调素水平均显著低于CLP组,且CLP+川芎嗪组小鼠血清TNF-α、IL-1、IL-6水平显著低于CLP+铁调素抑制剂组,铁调素水平显著低于CLP+铁调素抑制剂组,差异均有统计学意义(均P<0.05)。CLP+铁调素抑制剂组和CLP+川芎嗪组术后48 h肝组织铁调素表达水平显著低于CLP组,高于假手术组,差异均有统计学意义(均P<0.05);而CLP+铁调素抑制剂组p-STAT和p-JAK蛋白表达水平与CLP组相比,差异均无统计学意义(均P>0.05);CLP+川芎嗪组p-STAT和p-JAK蛋白表达水平显著低于CLP+铁调素抑制剂组和CLP组,高于假手术组,差异均有统计学意义(均P<0.05)。结论川芎嗪能够通过抑制JAK/STAT磷酸化而减少铁调素在小鼠肝组织中的表达,从而减轻肝脏损及全身炎性损伤。Objective To investigate the effect of ligustrazine on the expression of hepcidin in septic mice and its mechanism.Methods Forty four C57BL/6J male mice were randomly divided into sham operation group,intestinal perforation(CLP)group,CLP+calmodulin inhibitor group and CLP+ligustrazine group,with 11 mice in each group.The sepsis model was induced by cecal ligation and puncture(CLP).The bacterial loads in blood and peritoneal fluid were measured at 12h after CLP operation or sham operation.The 4-day survival rate was observed,the serum levels of biochemical indexes and inflammatory factors were measured by ELISA,and the expressions of hepcidin and JAK/STAT phosphorylation proteins in liver were detected by Western blot.Results No bacteria were detected in blood and peritoneal fluid of sham operated mice at 12 h after operation.The bacterial loads in blood and peritoneal fluid were(15.0±1.3)×10^(3)/ml and(8.6±1.0)×10^(3) CFU/ml in CLP group at 12 h after operation.The 4-day survival rates of CLP+hepcidin inhibitor group and CLP+ligustrazine group were 75.0%(6/8)and 87.5%(7/8),respectively,which were higher than that in CLP group[0.0%(0/8),P<0.01].The levels of ALT,AST,TNF-α,IL-1,IL-6 and calmodulin in CLP+hepcidin inhibitor group and CLP+ligustrazine group were significantly lower than those in CLP group,and the levels of serum TNF-αin CLP+ligustrazine group were significantly lower than those in CLP group.The levels of IL-1 and IL-6 were significantly lower than those in CLP+hepcidin inhibitor group,and the levels of ferritin were significantly lower than those in CLP+hepcidin inhibitor group(all P<0.05).Western blot showed that the expression of hepcidin in CLP+hepcidin inhibitor group and CLP+ligustrazine group was significantly lower than that in CLP group and higher than that in sham operation group(all P<0.05).There was no significant difference in the expression of p-STAT and p-JAK proteins between CLP+hepcidin inhibitor group and CLP group(P>0.05).The expression of p-STAT and p-JAK protein in CLP+ligus

关 键 词：川芎嗪 脓毒症小鼠 铁调素 JAK/STAT通路 

分 类 号：R285.5[医药卫生—中药学]