祛风宣肺方通过背根神经反射降低咳嗽敏感性的作用机制研究
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国家自然科学基金面上项目(81373588);北京市自然科学基金项目(7192115,7184224);北京中医药大学东方医院“1166”人才培养项目(040204001001002012);中国民族医药学会科研项目(2021Z1215-510201)


Qufeng Xuanfei Decoction Reduces Cough Sensitivity via Dorsal Root Reflex
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    摘要:

    目的:探讨祛风宣肺方对咳嗽敏感性增高豚鼠背根神经节中瞬时受体电位香草酸亚型1(TRPV1)、P物质(SP)、降钙素基因相关肽(CGRP)蛋白及基因的作用,进一步研究祛风宣肺方在慢性咳嗽中的作用机制。方法:将48只SPF级雄性健康豚鼠随机分为正常对照组(生理盐水)、模型组(生理盐水)、西药组(Capsazepine)、中药组(祛风宣肺方),采用卵蛋白致敏的方法建立咳嗽敏感性增高豚鼠模型。药物干预1周后辣椒素雾化法测定各组豚鼠的咳嗽次数,实时PCR法测定背根节中TRPV1、SP、CGRP mRNA水平,蛋白印迹法测定背根节中TRPV1、NK1-R、CGRP蛋白表达。结果:与正常对照组比较,模型组咳嗽次数增加,背根节中TRPV1、SP、CGRP mRNA表达增加,TRPV1、NK-1R、CGRP蛋白表达升高(均P<0.01)。与模型组比较,西药组、中药组咳嗽次数降低(P<0.05),背根节中TRPV1、SP、CGRP mRNA表达下降(P<0.01),西药组背根节中TRPV1、NK-1R、CGRP蛋白表达下降(P<0.05),中药组背根节中NK-1R、CGRP蛋白表达下降(P<0.05),TRPV1蛋白表达与模型组比较,差异无统计学意义(P>0.05)。结论:抑制TRPV1通道,抑制背根神经反射进而降低气道神经源性炎症可能是祛风宣肺方的重要疗效机制之一。

    Abstract:

    To investigate the effects of Qufeng Xuanfei Decoction on the expression of transient receptor potential vanilloid subfamily 1(TRPV1),substance P(SP),and calcitonin gene-related peptide(CGRP) in the dorsal root ganglion(DRG) of the guinea pig model of cough hypersensitivity,and decipher the mechanism of Qufeng Xuanfei Decoction in relieving chronic cough.Methods:Forty-eight SPF-grade healthy male guinea pigs were randomized into normal control(normal saline),model(normal saline),Western medicine(capsazepine),and Chinese medicine(Qufeng Xuanfei Decoction) groups.The guinea pig model of cough hypersensitivity was established by sensitization with ovalbumin.After one week of drug intervention,the cough times of guinea pigs in each group were measured by capsaicin atomization.The mRNA levels of TRPV1,SP,and CGRP in the DRG were measured by RT-PCR,and the protein levels of TRPV1,NK-1 receptor(NK1-R),and CGRP in the DRG were measured by Western blotting.Results:Compared with the normal control group,the model group showed increased cough times,up-regulated mRNA levels of TRPV1,SP,and CGRP and up-regulated protein levels of TRPV1,NK-1R,and CGRP in the DRG(all P<0.01).Compared with the model group,both Western medicine and Chinese medicine reduced the cough times(P<0.05) and down-regulated the mRNA levels of TRPV1,SP,and CGRP in the DRG(P<0.01).In addition,the Western medicine down-regulated the protein levels of TRPV1,NK-1R and CGRP in the DRG(P<0.05) and the Chinese medicine down-regulated the protein levels of NK-1R and CGRP(P<0.05).The protein level of TRPV1 showed no significant difference between the Chinese medicine group and the model group(P>0.05).Conclusion:Qufeng Xuanfei Decoction may block the TRPV1 channel and inhibit the dorsal root reflex to reduce the neurogenic inflammation in the airway.

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李雅兰,马建岭,史利卿,王颖,罗敬月,罗景舒,李扭扭.祛风宣肺方通过背根神经反射降低咳嗽敏感性的作用机制研究[J].世界中医药,2023,(21).

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  • 收稿日期:2022-04-11
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  • 在线发布日期: 2023-12-29
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