本文關鍵詞： 薄荷酮 內毒素 炎癥因子 NLRP炎癥小體 cathepsin-B PXR　出處：《中國藥理學通報》2017年02期 　論文類型：期刊論文

【摘要】：目的觀察薄荷酮對內毒素(LPS)致炎癥模型小鼠的保護作用,并初步探討與NLRP3炎癥小體激活相關的調控作用機制。方法♂C57BL/6J小鼠按體質量分層隨機分為空白對照組、模型對照組、地塞米松組(5 mg·kg~(-1))、薄荷酮0.25 g·kg~(-1)及0.5 g·kg~(-1)劑量組。除地塞米松組實驗當日腹腔注射給藥1次外,其余各組小鼠連續(xù)灌胃給藥5 d,每天1次。各組小鼠末次給藥30 min后,除空白組小鼠外,其余各組小鼠腹腔注射LPS(15 mg·kg~(-1),10 m L·kg~(-1))制備炎癥反應模型,造模12 h后,小鼠取血分離血清,采用ELISA及液相蛋白芯片技術測定炎癥因子IL-18、IL-1β、IL-5、TNF-α、IFN-γ、粒細胞集落刺激因子(G-CSF)、粒細胞-巨噬細胞集落刺激因子(GM-CSF)及巨噬細胞炎性蛋白-1β(MIP-1β)的水平;取小鼠全血進行白細胞(WBC)計數(shù);剖取肺組織計算肺臟指數(shù),并測定肺組織中NO含量,進行肺組織病理組織學檢查;RT-PCR法檢測肺組織中NLRP3、caspase-1及IFN-α mRNA表達;免疫組化法觀察肺組織中cathepsin B、P2X7R蛋白表達。結果 0.5 g·kg~(-1)薄荷酮明顯降低內毒素致炎癥模型小鼠血清IL-18、IL-1β、IL-5、TNF-α、IFN-γ、G-CSF、GM-CSF、MIP-1β的水平(P0.05或P0.01),下調模型小鼠肺組織NLRP3、IFN-α mRNA表達及cathepsin-B、P2X7R蛋白表達(P0.05或P0.01),明顯降低模型小鼠肺組織中NO的含量(P0.05);0.25 g·kg~(-1)薄荷酮明顯降低模型小鼠血清中IL-1β、IL-5、TNF-α、MIP-1β含量(P0.05),下調肺組織中P2X7R蛋白表達及NO水平(P0.05或P0.01);病理組織學檢查顯示0.5、0.25 g·kg~(-1)薄荷酮能明顯減少肺組織切片中嗜中性粒細胞數(shù)量(P0.01),減輕肺泡膈的增厚;薄荷酮對模型小鼠全血白細胞計數(shù)與肺指數(shù)的升高表現(xiàn)出降低趨勢。結論薄荷酮對內毒素致炎癥模型小鼠有保護作用,能抑制血清多種炎性細胞因子的釋放而減輕肺部炎性損傷,該作用可能與干擾NLRP3炎癥小體的激活有關。
[Abstract]:Objective to observe the protective effect of menthone on inflammatory model mice induced by lipopolysaccharide (LPS), and to explore the regulatory mechanism related to the activation of NLRP3 inflammatory bodies. 鈾侰57BL / 6J mice were randomly divided into control group, model control group, dexamethasone group (5 mg 路kg ~ (-1)), menthol 0.25 g 路kg ~ (-1) and 0.5 g 路kg ~ (-1)). The other mice were given orally for 5 days, once a day. After the last administration for 30 min, the other groups were injected intraperitoneally with LPS(15 mg 路kg ~ (-1) and 10 mL 路kg ~ (-1) 路kg ~ (-1) LPS(15 for 30 min. After 12 hours, the serum samples were collected from the mice. ELISA and liquid-phase protein chip technique were used to detect the levels of IL-18, IL-1 尾, IL-5, TNF- 偽, G-CSF- 緯, G-CSF-, GM-CSFand macrophage inflammatory protein 1 尾 -MIP-1 尾, and WBCcount in whole blood of mice. Lung index was calculated and no content in lung tissue was measured. The expression of NLRP3caspase-1 and IFN- 偽 mRNA in lung tissue was detected by RT-PCR. Results 0. 5 g 路kg-1) menthone significantly decreased the level of IL-18, IL-1 尾, IL-5, TNF- 偽, IFN- 緯, G-CSFGM-CSFMIP-1 尾, P0.01, down-regulated the expression of NLRP3mIFN- 偽 IFN- 偽 and cathepsin-BP2X7R protein in lung tissue of model mice by immunohistochemical method, and down-regulated the expression of NLRP3- IFN- 偽 mRNA and cathepsin-BP2X7R protein by P05 or P0.01. P0.01A significantly decreased the content of no in the lung tissue of the model mice. (P0.05g 路kg-1) menthone significantly decreased the serum IL-1 尾 -IL-5TNF- 偽 -MIP-1 尾 content, down-regulated the expression of P2X7R protein and the level of no (P0.05 or P0.01A) in the lung tissue of the model mice, and the pathological examination showed that it was 0.5U 0.25 g 路kg-1) menthol could be used in the lung tissue of the model mice, and the expression of P2X7R protein and the level of no in the lung tissue were down-regulated (P0.05g 路kg-1, P0.05g 路kg-1). The number of neutrophilic granulocytes in lung tissue sections was significantly reduced (P 0.01), and the thickening of alveolar diaphragm was alleviated. Menthone showed a decreasing trend on the increase of whole blood leukocyte count and lung index in model mice. Conclusion menthone has protective effect on endotoxin-induced inflammatory model mice. It can inhibit the release of many inflammatory cytokines in serum and alleviate the pulmonary inflammatory injury, which may be related to interfering with the activation of NLRP3 inflammatory corpuscles.
【作者單位】： 成都中醫(yī)藥大學藥學院中藥材標準化教育部重點實驗室四川省中藥資源系統(tǒng)研究與開發(fā)利用省部共建國家重點實驗室培育基地;
【基金】：國家自然科學基金資助項目(No81473399) 國家基礎科學人才培養(yǎng)基金項目(NoJ1310034-09)
【分類號】：R285.5;R-332

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