射干提取物抗豚鼠咳嗽模型气道炎症机制研究  

Study on Mechanism of Anti-Guinea Pig Airway Inflammation by Shegan(Belamcanda chinensis)

作　　者：汪天青 张颖[1] 姜鸿[1] 李国信[1] WANG Tianqing;ZHANG Ying;JIANG Hong;LI Guoxin(Liaoning Province Chinese Medicine Research Institute,Shenyang 110034,Liaoning,China)

机构地区：[1]辽宁省中医药研究院

出　　处：《中华中医药学刊》2019年第8期1880-1885,I0011,I0012,共8页Chinese Archives of Traditional Chinese Medicine

基　　金：国家“十三五”重大新药创制项目(2017ZX09301019);国家“十二五”重大新药创制项目(2012ZX09303-017);国家自然科学基金面上项目(81273927)

摘　　要：目的:研究射干提取物对呼吸道合胞病毒(RSV)感染豚鼠咳嗽模型肺组织中COX-2和5-LOX蛋白表达水平及相关通路代谢物的影响,探讨其对气道炎症的相关抗炎机制。方法:将40只豚鼠随机分为4组,每组10只:空白组、模型组、射干组和阳性组。采用烟熏配合RSV滴鼻,建立RSV感染豚鼠咳嗽模型;给予射干提取物和肺宁片进行干预治疗,采用Western-blot法检测模型动物给药治疗后肺组织中COX-2和5-LOX蛋白表达水平;采用HPLC-MS-MS法,检测花生四烯酸COX通路中的代谢产物TXB2、PGD2、PGE2,CYP通路中的代谢产物8,9-DHET、11,12-DHET、14,15-DHET及LOX通路中的代谢产物5HETE、15HETE的变化,进而探讨射干抗炎作用机制。结果:与正常对照组比较,模型组COX-2、5-LOX蛋白表达水平显著升高(P<0.05)。与模型组相比,射干组COX-2蛋白表达水平显著降低(P<0.05),而5-LOX蛋白表达无显著差异(P>0.05)。花生四烯酸代谢产物含量测定结果表明:在COX代谢途径研究中,模型组肺组织中PGD2、TXB2、11HETE含量与空白组相比显著升高(P<0.05),给予射干提取物治疗后各代谢产物含量均下降(P<0.05)。在LOX代谢途径研究中,模型组肺组织中5HETE和15HETE含量与空白组相比显著升高(P<0.05),给予射干提取物治疗后各代谢产物含量有降低趋势,但是没有统计学意义。在CYP450途径中,模型组肺组织中16HETE含量与空白组相比显著升高(P<0.05),给予射干提取物治疗后11,12-DHET、14,15-DHET含量显著降低(P<0.05),16HETE含量有降低趋势,但是没有统计学意义(P>0.05)。结论:射干主要通过干预花生四烯酸COX-2、CYP450信号通路达到对豚鼠咳嗽模型气道炎症的抗炎、止咳作用。Objective:To study the effects of the dried extract of Shegan(Belamcanda chinensis) on the expressions of COX-2 and 5-LOX protein and related pathway metabolites in lung tissue of respiratory syncytial virus(RSV) infected guinea pig cough modeland explore its anti-inflammatory mechanism related to airway inflammation. Methods:Forty guinea pigs were randomly divided into 4 groups, 10 in each group: control group, model group, Shegan(Belamcanda chinensis) group and positive group. RSV-infected guinea pig cough model was established by using smoked and RSV nasal drops. Shegan(Belamcanda chinensis) extract and Feining Tablets were used for interventional treatment. Expression levels of the COX-2 and 5-LOX proteins in lung tissue were measured by Western-blot method. HPLC-MS-MS method was used to detect metabolites TXB2, PGD2 and PGE2 in the arachidonic acid COX pathway, metabolites in the CYP pathway 8,9-DHET, 11,12-DHET, 14,15-changes in the 5 HETE and 15 HETE metabolites in the DHET and LOX pathways, and then explored the mechanism of the anti-inflammatory effect.Results:Compared with the control group, the expression levels of COX-2 and 5-LOX in the model group were significantly increased(P<0.05). Compared with the model group, the expression level of COX-2 protein in the Shegan(Belamcanda chinensis) group was significantly lower(P<0.05), while the expression of 5-LOX protein was not significantly different(P>0.05). The content of arachidonic acid metabolites showed that the contents of PGD2, TXB2 and 11 HETE in the lung tissue of the model group were significantly higher than those in the control group(P<0.05). The content of each metabolite decreased after treatment with the dried extract of(Belamcanda chinensis)(P<0.05). In the LOX metabolic pathway study, the levels of 5 HETE and 15 HETE in the lung tissue of the model group were significantly higher than those in the control group(P<0.05). The content of each metabolite decreased after treatment with the dried extract of Shegan(Belamcanda chinensis), but it

关 键 词：射干 炎症 机制 花生四烯酸 

分 类 号：R285.5[医药卫生—中药学]