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探讨反式茴香脑(trans-anethol,ANE)对慢性阻塞性肺疾病(chronicobstructivepulmonarydisease, COPD)的治疗作用,以及对胆碱能抗炎途径的调节作用。通过香烟烟雾和脂多糖(lipopolysaccharide, LPS)诱导COPD Sprague-Dawley大鼠模型。每天按照100 mg/kg的剂量对大鼠灌胃ANE,另外,在ANE治疗前30 min对大鼠腹膜内注射选择性α7nAChR拮抗剂α-真菌毒素组(α-BGT, 1.0μg/kg),共治疗4周。治疗后,检查大鼠的肺功能和肺组织病理。酶联免疫吸附法测定肺组织中的乙酰胆碱(acetylcholine, ACh)、乙酰胆碱酯酶(acetylcholinesterase, AChE)、白细胞介素6 (interleukin-6, IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平。通过RT-PCR、蛋白质印迹和免疫组化观察大鼠肺组织中α7nAChR、JAK2、STAT3和NF-κB的表达。研究显示,ANE提高了COPD大鼠的用力肺活量(forced vital capacity, FVC)、第0.1秒用力呼气量(FEV 0.1)、第0.3秒用力呼气量(FEV 0.3)、FVC 0.1占FVC比值(FEV 0.1/FVC)、FEV 0.3占FVC比值(FEV 0.3/FVC)(p<0.05)。XANE升高了COPD大鼠肺组织中的ACh和AChE水平(p<0.05)。ANE降低了COPD大鼠肺组织中TNF-α和IL-6的水平(p<0.05)。ANE上调了COPD大鼠肺组织中α7nAChR的表达,但下调了JAK2、STAT3和NF-κB的表达(p<0.05)。α-BGT处理可逆转ANE对大鼠肺功能的保护作用(p<0.05)。反式茴香脑对COPD大鼠的治疗作用可能与其对胆碱能抗炎途径的激活有关。
Abstract：To explore the therapeutic effect of trans-anethole(ANE) on chronic obstructive pulmonary disease(COPD) and the regulatory effect of cholinergic anti-inflammatory pathway. COPD Sprague-Dawley rat model was induced by cigarette smoke and lipopolysaccharide. Rats were intragastrically fed ANE at a dose of 100 mg/kg daily. In addition, the selective α7 nAChR antagonist α-mycotoxin group(α-BGT, 1.0 μg/kg) was intraperitoneally injected into the rats 30 min before ANE treatment. A total of 4 weeks of treatment. After treatment, the lung function and lung tissue pathology of the rats were examined. ELISA was used to determine the levels of acetylcholine(ACh), acetylcholinesterase(AChE), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in lung tissue. The expressions of α7 nAChR, JAK2, STAT3 and NF-κB in rat lung tissue were observed by RT-PCR,Western blotting and immunohistochemistry. Studies showed that ANE increases forced vital capacity(FVC),forced vital capacity at 0.1 seconds(FEV 0.1), forced vital capacity at 0.3 seconds(FEV 0.3), FEV 0.1/FVC and FEV 0.3/FVC in COPD rats(p<0.05). ANE increased ACh and AChE levels in lung tissue of COPD rats(p<0.05).ANE reduced the levels of TNF-α and IL-6 in the lung tissue of COPD rats(p<0.05). ANE up-regulated the expression of α7 nAChR in the lung tissue of COPD rats, but down-regulated the expression of JAK2, STAT3 and NF-κB(p<0.05). α-BGT treatment reversed the protective effect of ANE on lung function in rats(p<0.05). The therapeutic effect of trans-anethole on COPD rats may be related to the activation of the cholinergic anti-inflammatory pathway.
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基本信息:
DOI：10.13417/j.gab.039.003256
中图分类号:R563.9;R-332
引用信息:
[1]白俊云,袁文云,张龙瑜,等.反式茴香脑对慢性阻塞性肺疾病大鼠模型胆碱能抗炎途径的调节作用[J].基因组学与应用生物学,2020,39(07):3256-3263.DOI:10.13417/j.gab.039.003256.
2020-07-25
2020-07-25