南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (6): 824-831.doi: 10.12122/j.issn.1673-4254.2022.06.05

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旋毛虫肌幼虫排泄分泌蛋白对脓毒症诱发的小鼠心肌损伤有保护作用

袁 圆，年 峰，李徽徽，杨慧娟，吴玉芝，马梦禧，汪开贵，陈雪玲，张自强，栗 根，杨小迪，吴 强   

  1. 蚌埠医学院人体解剖学教研室，附属蚌埠第三人民医院肿瘤内科，组织胚胎学教研室，第一附属医院肾病科，免疫学实验中心，病原生物学教研室，第一附属医院重症医学科，安徽 蚌埠 233000
  • 出版日期:2022-06-20 发布日期:2022-06-28

Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice

YUAN Yuan, NIAN Feng, LI Huihui, YANG Huijuan, WU Yuzhi, MA Mengxi, WANG Kaigui, CHEN Xueling, ZHANG Ziqiang, LI Gen, YANG Xiaodi, WU Qiang   

  1. Department of Human Anatomy, Department of Oncology, Bengbu Third People's Hospital Affiliated to Bengbu Medical College, Bengbu 233000, China; Department of Histology and Embryology, Immunology Experiment Center, Department of Pathogen Biology, Bengbu Medical College, Bengbu 233000, China; Department of Nephrology, Department of Intensive Care Medicine, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
  • Online:2022-06-20 Published:2022-06-28

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摘要： 目的 观察旋毛虫肌幼虫排泄分泌蛋白（Ts-MES）对脓毒症诱发的小鼠心肌损伤的保护作用。方法 80只雄性BALB/c小鼠随机分为4组，各组20只，分别为假手术组（A组）、心肌损伤模型组（B组）、Ts-MES治疗组（C组）和地塞米松对照组（D组）。B、C、D组采取盲肠结扎穿孔术构建脓毒症诱发的心肌损伤小鼠模型，A组只行开腹探寻，不结扎和穿刺盲肠。术后40 min，A、 B组腹腔注射150 μL PBS，C组腹腔注射含20 μg Ts-MES的等量PBS，D组腹腔注射含地塞米松（0.3 mg/kg）的等量PBS。术后12 h，每组随机抽取6只小鼠进行超声心动图检测，另抽取8只用于观察72 h生存率。剩余的6只小鼠通过HE染色评价心肌病理变化，ELISA法检测血清中NTPro-BNP和cTnI水平，ELISA法和qRT-PCR法分别检测血清和心肌组织中TNF-α、IL-6、IL-10、TGF-β的表达。结果 B组小鼠的心功能指标（LVEF、LVFS、E/A）及72 h生存率较A组显著下降（P<0.001），心肌病理损伤评分及血清中NTPro-BNP和cTnI水平明显升高（P<0.01）；与B组相比，C、D两组小鼠的心功能指标和72 h生存率明显回升（P<0.05），心肌病理损伤评分及血清中NTPro-BNP和cTnI水平明显降低（P<0.05）。小鼠血清和心肌组织中TNF-α和IL-6水平比较：B组小鼠血清和心肌组织中TNF-α和IL-6水平较A组显著升高（P<0.001），C、D两组较B组显著下降（P<0.05）；IL-10和TGF-β水平：C组较B组显著升高（P<0.05），D组较B组虽有增高但无统计学差异。结论 Ts-MES可抑制促炎细胞因子的表达并促进调节性细胞因子的表达，进而保护脓毒症诱发的小鼠心肌损伤。

关键词: 旋毛虫；排泄分泌蛋白；脓毒症心肌损伤

Abstract: Objective To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice. Methods Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR. Results Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P<0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P<0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P<0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P<0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P<0.001), which were significantly lowered by treatment with TS-MES (P<0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P<0.05). Conclusion Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.

Key words: Trichinella spiralis; excretory-secretory proteins; sepsis myocardial injury