甜菜碱对脓毒症小鼠心脏保护作用及其抗炎机制
Protective effect of betaine on hearts of mice with sepsis and itsanti-inflammatory mechanisms
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摘要: 目的 初步探讨甜菜碱(Betaine)对脓毒症小鼠的心脏保护作用及潜在抗炎机制。方法 采用盲肠结扎穿刺术(CLP)构建小鼠脓毒症模型,将雄性C57BL/6小鼠随机分为5组,生存率检测每组20只,其余指标检测每组10只,包括假手术组(Ctrl)、脓毒症模型组(CLP)及脓毒症+Bet低、中、高剂量干预组(CLP+Bet-L, 50 mg/kg; CLP+Bet-M, 100 mg/kg; CLP+Bet-H, 200 mg/kg)。造模前1 h对干预组小鼠腹腔注射Bet,并于术后24、48、72 h补药维持药效。于造模后特定时间,分别检测小鼠心功能、血清肌酸激酶同工酶(CK-MB)水平、心肌组织病理及炎症因子mRNA表达,连续7 d观察小鼠生存率。结果 与对照组相比,CLP组小鼠7 d生存率降低,心功能指标左心室射血分数(LVEF)、二尖瓣口舒张早期/晚期血流速度(E/A)比值下降,血清CK-MB水平、心肌组织白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)、IL-1β mRNA表达升高(均P<0.05),心肌出现炎症浸润及病理损伤。与CLP组相比,各Bet干预组小鼠生存率提升、心功能改善、CK-MB水平及促炎因子表达下调,心肌病理损伤减轻,且改善效果呈剂量依赖性(P<0.05)。结论 Bet通过抑制脓毒症小鼠心肌过度炎症反应,减少炎症因子释放与心肌损伤,进而改善心功能、提高小鼠生存率,且保护作用具有剂量依赖性。Abstract: OBJECTIVE To preliminarily explore the protective effect of betaine on hearts of the mice with sepsis and observe the potential anti-inflammatory mechanisms. METHODS The sepsis mice models were constructed by cecal ligation and puncture (CLP). The male C57BL/6 mice were randomly divided into 5 groups, the survival rate was detected for 20 mice of each group, and the rest of indicators were detected for 10 mice of each group, including the sham surgery group (Ctrl), the sepsis model group (CLP), and the sepsis plus low-dose, medium-dose and high-dose Bet intervention groups (CLP+Bet-L, 50 mg/kg; CLP+Bet-M, 100 mg/kg; CLP+Bet-H, 200 mg/kg). The intervention group was treated with abdominal injection of Bet 1 hour before the modeling and was given additional booster injections to maintain the therapeutic effect after the surgery for 24, 48, and 72 hours. The cardiac function, serum creatine kinase MB (CK-MB) level, pathological characteristics of myocardial tissues and expression of inflammatory factor mRNA were detected respectively at certain time points after the modeling. The survival rates of the mice were observed for 7 consecutive days. RESULTS The 7-day survival rate of the mice was lower in the CLP group than in the control group; the cardiac function indicators such as left ventricular ejection fraction (LVEF) and ratio of early to late diastolic blood flow velocity at the mitral valve orifice (E/A) were lower in the CLP group than in the control group; the serum CK-MB level and the expression levels of myocardial tissue interleukin (IL)-6, tumor necrosis factor-α(TNF-α) and IL-1β mRNA were higher in the CLP group than in the control group (all P<0.05). The mice of the CLP group had myocardial inflammatory infiltration and pathological damage. The Bet intervention groups had the higher survival rate, more improve cardiac function, lower CK-MB level and expression levels of proinflammatory factors, and milder pathological damage of myocardial tissues than the CLP group did, and the improvement effect was dose-independent (P<0.05). CONCLUSIONS Bet improves the cardiac function and raises the survival rate of the mice by inhibiting the excessive myocardial inflammatory response of the mice, reducing the release of inflammatory factors and myocardial damage. The protective effect is dose-independent.
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