N-乙酰半胱氨酸对脓毒症大鼠急性肺损伤的影响及其与自噬的关系  

Effect of N-acetylcysteine on acute lung injury in sepsis rats and its relationship with autophagy

作　　者：蔡江红[1] 杨国辉[1] CAI Jianghong;YANG Guohui(Guizhou Medical University, Guiyang 550004, China)

机构地区：[1]贵州医科大学

出　　处：《山东医药》2019年第17期40-43,共4页Shandong Medical Journal

摘　　要：目的 观察N-乙酰半胱氨酸(NAC)对脓毒症大鼠急性肺损伤的影响,并分析其与自噬的关系。方法 取24只雄性大鼠,随机分为假手术组、模型组、NAC组和3-甲基腺嘌呤(3-MA)干预组。采用盲肠结扎穿孔(CLP)法制备脓毒症模型,假手术组仅取出盲肠,不结扎、穿孔。NAC组于术后1、4、8、12、16、20h分别给予NAC20mg/kg皮下注射,3-MA干预组于术后1h给予自噬抑制剂3-MA10mg/kg腹腔注射;3-MA干预组、假手术组、模型组、NAC组各时间点用等量生理盐水皮下注射。24h后测算肺组织湿/干比重(W/D)评价肺水肿程度,采用HE染色观察肺组织病理变化,ELISA法测定肺组织中TNF-α、IL-6水平,Western blotting法检测肺组织自噬相关蛋白微管相关蛋白1轻链3Ⅱ(LC3Ⅱ)、Beclin-1表达,qRT-PCR法检测肺组织LC3Ⅱ、Beclin-1 mRNA表达。结果 与假手术组比较,模型组肺组织W/D增加,肺损伤评分升高,肺组织中TNF-α、IL-6表达升高,肺组织中LC3Ⅱ、Beclin-1蛋白及mRNA表达升高(P均<0.05);与模型组比较,NAC组肺组织W/D下降,肺损伤评分降低,肺组织中TNF-α、IL-6表达下降,肺组织中LC3Ⅱ、Beclin-1蛋白及mRNA表达下降(P均<0.05)。3-MA干预组上述指标与NAC组比较,差异无统计学意义(P均>0.05)。结论 NAC能够减轻脓毒症所致急性肺损伤引起的肺水肿,抑制肺组织炎症反应;其机制可能是通过抑制自噬来发挥肺保护作用。Objective To investigate the effect of N-acetylcysteine (NAC) on the acute lung injury in sepsis rats and its relationship with autophagy. Methods Twenty-four male rats were randomly divided into 4 groups: sham operation control group (group S), sepsis model group (CLP group), NAC treatment group (NAC group), and 3-methyladenine intervention group (3-MA group). The septic model was established by cecal ligation and puncture (CLP). The rats in the NAC group were subcutaneously injected with NAC (20 mg/kg) at 1, 4, 8, 12, 16, and 20 h after surgery. After 1 h surgery, intervention was performed with 3-MA (10 mg/kg);rats in the 3-MA group, group S and CLP group were subcutaneously injected with the same amount of normal saline at each time point in the NAC group. After 24 h, wet to dry rate (W/D)was measured to evaluate the degree of pulmonary edema;pathological changes of lung tissues were observed by HE staining;TNF-α and IL-6 expression levels in the lung tissues were determined by ELISA;the protein expression of microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ) and Beclin-1 in the lung tissues was detected by Western blotting, and the mRNA expression of LC3Ⅱ and Beclin-1 was detected by qRT-PCR. Results Compared with the group S, W/D increased, the lung injury score increased, TNF-α, IL-6, and the protein and mRNA expression of LC3Ⅱ and Beclin-1 in lung tissues increased in the CLP group(all P <0.05). Compared with the CLP group, the W/D decreased, the lung injury score decreased, TNF-α, IL-6, and the protein and mRNA expression of LC3Ⅱ and Beclin-1 in the lung tissues decreased in the NAC group(all P <0.05).There were no significant differences in the above indexes between 3-MA group and NAC group (all P > 0.05 ). Conclusion NAC may alleviate the pulmonary edema in rats with acute lung injury caused by sepsis by inhibiting autophagy and reducing inflammation.

关 键 词：脓毒症 急性肺损伤 N-乙酰半胱氨酸 自噬 3-甲基腺嘌呤 微管相关蛋白1轻链3Ⅱ BECLIN-1 

分 类 号：R631[医药卫生—外科学]