文章摘要
王馨璐,汪海慧,沈一凡,李万义,曲立哲.抗炎合剂对脓毒症小鼠心肌损伤的保护作用及机制[J].,2023,(24):4627-4632
抗炎合剂对脓毒症小鼠心肌损伤的保护作用及机制
Effects of Anti-inflammation Mixture on Sepsis-induced Myocardial Injury in Mice and its Mechsnisms
投稿时间:2023-05-22  修订日期:2023-06-14
DOI:10.13241/j.cnki.pmb.2023.24.005
中文关键词: 抗炎合剂  脓毒症  心肌损伤  沉默信息调节因子1
英文关键词: Anti-inflammation mixture  Sepsis  Myocardial injury  Sirtuin [silent mating type information regulation 2 homolog] 1
基金项目:海派中医流派传承延伸计划项目(ZY(2021-2023)-0209-11);上海中医药大学理科预算内项目(2020LK067)
作者单位E-mail
王馨璐 上海市中医医院 上海 200071 786000786@qq.com 
汪海慧 上海市中医医院 上海 200071  
沈一凡 上海市中医医院 上海 200071  
李万义 上海市中医医院 上海 200071  
曲立哲 上海市中医医院 上海 200071  
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中文摘要:
      摘要 目的:探讨抗炎合剂对脓毒症致心肌损伤的保护作用及可能机制。方法:将32只体重22~25 g的雄性C57小鼠随机分为4组:正常组、假手术组、模型组(脓毒症模型)、抗炎合剂组。采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)建立脓毒症模型,模型组、抗炎合剂组在造模后分别用生理盐水、抗炎合剂(Anti-inflammation mixture,AIM)对大鼠进行干预。正常组:正常进食饮水;假手术组:假手术前每天给予生理盐水(1.4 mL/100 g),并腹腔注射生理盐水(5 mg/kg)每日1次,连续3日。第4日行假手术;模型组(CLP组):CLP术前给予生理盐水(1.4 mL/100 g),每天1次,并腹腔注射生理盐水(5 mg/kg)每日1次,连续3日。第4日CLP;抗炎合剂组:CLP术前给予中药抗炎合剂(1.4 mL/100 g),每天1次,并腹腔注射生理盐水(5 mg/kg)每日1次,连续3日。第4日行CLP;各组分别于手术后24小时行标本采集,采用HE染色和TUNEL染色观察小鼠心肌组织损伤情况,同时检测小鼠血清肿瘤坏死因子-α(TNF-α)和炎症因子白细胞介素-1β(IL-1β)水平。结果:与正常对照组或假手术组相比,CLP模型组小鼠的心肌组织出现大量炎性细胞浸润,心肌细胞凋亡率显著升高(P<0.01);而抗炎合剂组相较于CLP模型组心肌细胞凋亡率显著下降(P<0.01)。与正常对照组或假手术组相比,CLP模型小鼠血清TNF-α、IL-1β水平显著升高(P<0.001),而中药抗炎合剂组TNF-α、IL-1β水平相较于模型组显著降低(P<0.01)。此外,与正常对照组和假手术组相比,模型组SIRT1 mRNA水平和蛋白表达水平显著降低,抗炎合剂显著提高SIRT1的mRNA和蛋白表达水平。结论:抗炎合剂可能通过提高SIRT1的表达,抑制CLP脓毒症小鼠的炎症反应,进而减轻心肌损伤。
英文摘要:
      ABSTRACT Objective: To investigate the protective effects of anti-inflammatory mixture of traditional Chinese medicine on myocardial injury caused by sepsis and its mechanisms. Methods: A total of 32 mice were randomly assigned into 4 groups: normal control group, sham operation group, and model group (sepsis group), and anti-inflammatory mixture group. After cecal ligation and perforation (CLP), rats in the sepsis group and anti-inflammatory mixture group were given normal saline, anti-inflammatory mixture respectively. Normal saline (1.4 mL/100 g) was given once a day before sham operation, and normal saline(5 mg/kg) was intraperitoneally injected once a day for 3 consecutive days. Sham operation was performed on the fourth day; In the model group (sepsis group), CLP mice were given normal saline (1.4 mL/100 g) once a day and intraperitoneal injection of normal saline (5 mg/kg) once a day for 3 consecutive days. In the anti-inflammatory mixture group: anti-inflammatory mixture (1.4 mL/100 g) was given once a day before surgery, and normal saline(5 mg/kg) was given once a day for 3 consecutive days. Specimens were collected at 24 hours after operation in each group. HE staiing and TUNEL staining were used to observe the myocardial tissue damage, and serum levels of tumor necrosis factor-α (TNF-α) and inflammatory factor interleukin-1β (IL-1β) were detected. Results: Compared with the normal control group or sham group, significant damage of myocardial tissue was observed in CLP model group, a large number of inflammatory cells infiltrated, and myocardial cell apoptosis increased significantly (P<0.01); Compared with CLP model group, anti-inflammation mixture (AIM) group had less myocardial damage and the number of apoptotic myocardial cells significantly decreased (P<0.01). Compared with normal control group or sham group, serum levels of TNF-α and IL-1β in CLP model mice were significantly increased(P<0.001), and the levels of TNF-α and IL-1β in TCM AIM group were significantly decreased compared with model group(P<0.01). In addition, compared with normal control group and sham group, mRNA and protein expression levels of SIRT1 were significantly decreased in the model group, and AIM significantly improved SIRT1 transcription and protein expression levels. Conclusion: Anti-inflammation mixture could protect mice against sepsis-induced myocardial injury, which might be related to increase the expression of SIRT1 and decrease of inflammatory response.
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