脂多糖致兔急性呼吸窘迫综合征机制及姜黄素保护作用的研究

张明月; 孙军平; 于海容; 韩欣洁; 王浚宇; 汪建新

doi:10.3969/j.issn.2095-5227.2023.01.007

脂多糖致兔急性呼吸窘迫综合征机制及姜黄素保护作用的研究

Lipopolysaccharide-induced acute respiratory distress syndrome and protective effects of curcumin in rabbits

摘要

摘要:
背景急性呼吸窘迫综合征(acute respiratory distress syndrome，ARDS)是一种以高致死率为特点的临床常见危重症，缺乏有效治疗手段，因此深入研究与ARDS发生发展相关的作用机制，从而找到有效的治疗药物尤为迫切。
目的应用脂多糖(lipopolysaccharide，LPS)复制兔ARDS模型，探讨炎症介质在ARDS发生发展过程中的致病机制及姜黄素的保护作用。
方法 28只新西兰白兔随机分为对照(control，C)组、模型(model，M)组、模型 + 溶媒(vehicle，V)组和治疗(treatment，T)组，每组7只。用一次性静注LPS(720 μg/kg)方法复制ARDS模型。建模后，M组经腹腔注射0.9%氯化钠注射液(0.8 mL/kg)，V组经腹腔注射等量二甲基亚砜，T组经腹腔注射姜黄素溶液(0.8 mL/kg)。于实验后6 h，采用ELISA检测支气管肺泡灌洗液(bronchoalveolar lavage fluid，BALF)和肺组织IL-17、IL-22含量变化。
结果 M组、V组BALF内IL-17含量较C组增高(P＜0.05)，T组IL-17含量虽高于C组升，但差异无统计学意义(P＞0.05)。M组、V组BALF内IL-22含量较C组有所下降，而T组IL-22含量较C组升高，但差异均无统计学意义(P＞0.05)。M组、V组肺组织内IL-17含量较C组显著升高(P＜0.05)；T组较C组亦有升高，但差异无统计学意义(P＞0.05)。T组肺组织内IL-22含量较C组升高(P＜0.05)；M组、V组IL-22含量较C组有所下降，但差异无统计学意义(P＞0.05)。病理结果显示M组、V组可见明显肺损伤改变，而T组损伤程度明显轻于M组、V组。
结论姜黄素可对LPS诱导的ARDS产生保护作用，这些作用可能是通过减少炎性浸润、减少促炎细胞因子在肺气道中的产生与释放、上调抗炎因子的表达来实现。

Abstract:
Background Acute respiratory distress syndrome (ARDS) is a clinically common critical disease characterized by high mortality. There is currently a lack of more effective drug treatments. Therefore, it is particularly urgent to discover more mechanisms related to the occurrence and development of ARDS, so as to find effective therapeutic drugs.
Objective To use lipopolysaccharide (LPS) to replicate ARDS model of rabbits and then discuss the pathogenic mechanism of inflammatory mediators in the development of ARDS and the protective effect of curcumin.
Methods Twenty-eight New Zealand white rabbits were randomly divided into the control group (C), model group (M), model + vehicle group (V), and treatment group (T). The ARDS model was replicated by one-off intravenous injection of LPS (720 μg/kg). After modeling, group M was intraperitoneally injected with normal saline (0.8 mL/kg), group V was intraperitoneally injected with the same amount of dimethyl sulfoxide, and group T was intraperitoneally injected with curcumin solution (0.8 mL/kg). Contents of IL-17 and IL-22 in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA at 6h after the experiment.
Results The content of IL-17 in BALF of the group M and the group V was higher than that of the group C (P<0.05), and the content of IL-17 in the group T was higher than that in the group C, but the differences were not statistically significant (P>0.05). The content of IL-22 in BALF of the group M and the group V decreased compared with that of the group C, while the content of IL-22 of group T was higher than that of the group C, but the differences were not statistically significant (P>0.05). The content of IL-17 in lung tissue of the group M and the group V was significantly higher than that of the group C (P<0.05); and it was higher in the group T than that in the group C, without significant difference (P>0.05). The content of IL-22 in lung tissue of the group T was significantly higher than that of the group C (P<0.05), however, it decreased in the group M and the group V, without significant difference (P>0.05). The pathology showed obvious lung injury in the group M and the group V, while the damage in the group T was significantly lighter than that in the group M and the group V.
Conclusion Curcumin can protect ARDS induced by LPS, which may be achieved by reducing inflammatory infiltration and the production and release of pro-inflammatory cytokines in the lung airways, and up regulating anti-inflammatory factors.

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