摘要
目的探讨疏肝和胃方通过调控过氧化物酶体增殖物激活受体γ/类视黄醇X受体(PPAR-γ/RXR)信号通路缓解胃食管反流病(GERD)大鼠气道炎症的机制。方法采用食管下端盐酸灌注法构建GERD合并气道炎症大鼠模型。将50只SD雄性大鼠随机分为对照组、模型组、疏肝和胃方低剂量组(10.49 g/kg生药量)、疏肝和胃方高剂量组(20.98 g/kg生药量)和奥美拉唑组(3.67 mg/kg),每组10只,灌胃14 d。采用苏木精-伊红(HE)染色观察气管组织的病理学变化;采用RT-qPCR检测支气管肺泡灌洗液中炎症因子[白细胞介素(IL)-17、IL-33、诱导型一氧化氮合酶(iNOS)]以及抗炎因子[IL-10、克拉拉细胞蛋白16(CC16)、表面活性蛋白-D(SP-D)]的mRNA表达水平;采用免疫印迹法检测PPAR-γ、RXR-α、核因子-κB(NF-κB)、活化蛋白-1(AP-1)的蛋白相对表达量。结果HE染色结果显示,模型组可见大量炎症细胞浸润,疏肝和胃方低剂量组、高剂量组和奥美拉唑组炎症细胞浸润明显减少。与对照组比较,模型组支气管肺泡灌洗液中IL-17、IL-33、iNOS的mRNA表达水平升高,IL-10、CC16、SP-D的mRNA表达水平降低,PPAR-γ、RXR-α的蛋白相对表达量升高,NF-κB、AP-1的蛋白相对表达量降低,差异均有统计学意义(P<0.05)。与模型组比较,疏肝和胃方高剂量组和奥美拉唑组上述指标均有改善,差异有统计学意义(P<0.05)。结论疏肝和胃方可以有效缓解GERD大鼠气道炎症,其作用机制可能与激活PPARγ/RXR信号通路有关。
Objective To investigate the mechanism of liver-soothing and stomach-harmonizing recipe alleviating airway inflammation in rats with gastroesophageal reflux disease(GERD)by regulating peroxisome proliferator-activated receptorγ/retinoid X receptor(PPAR-γ/RXR)signaling pathway.Methods A rat model of GERD with airway inflammation was established by perfusion of hydrochloric acid into the lower esophagus.A total of 50 SD male rats were randomly divided into control group,model group,low-dose liver-soothing and stomach-harmonizing recipe group(10.49 g/kg crude drug dosage),high-dose liver-soothing and stomach-harmonizing recipe group(20.98 g/kg crude drug dosage),and omeprazole group(3.67 mg/kg),with 10 rats in each group.The rats were gavaged for 14 days.Hematoxylin and eosin(HE)staining was used to observe the pathological change in tracheal tissue.RT-qPCR was used to detect the mRNA expression levels of inflammatory cytokines[interleukin(IL)-17,IL-33,inducible nitric oxide synthase(iNOS)]and anti-inflammatory cytokines[IL-10,Clara cell 16-kDa protein(CC16),surfactant protein-D(SP-D)]in bronchoalveolar lavage fluid;the Western blot was used to detect the relative protein expression levels of PPAR-γ,RXR-α,nuclear factor-κB(NF-κB),and activator protein-1(AP-1).Results The HE staining results showed that a large number of inflammatory cell infiltrations were observed in the model group,while the inflammatory cell infiltrations were significantly reduced in the low-dose liver-soothing and stomach-harmonizing recipe group,high-dose liver-soothing and stomach-harmonizing recipe group,and omeprazole group.Compared with the control group,the mRNA expression levels of IL-17,IL-33 and iNOS in bronchoalveolar lavage fluid were significantly increased while the mRNA expression levels of IL-10,CC16 and SP-D were significantly decreased in the model group,and the relative protein expression levels of PPAR-γand RXR-αwere significantly increased,while the relative protein expression levels of NF-κB and AP-1 were significantly decreased in the model group(P<0.05).Compared with the model group,the above indicators were significantly improved in the high-dose liver-soothing and stomach-harmonizing recipe group and omeprazole group(P<0.05).Conclusion Liver-soothing and stomach-harmonizing recipe can effectively alleviate airway inflammation in rats with GERD,and its mechanism may be related to the activation of the PPAR-γ/RXR signaling pathway.
作者
郑有浩
传芸
郑加梅
ZHENG Youhao;CHUAN Yun;ZHENG Jiamei(Outpatient Department,Zunyi Hospital of Traditional Chinese Medicine,Zunyi,Guizhou,563000;Outpatient Department,Chishui Hospital of Traditional Chinese Medicine,Chishui,Guizhou,564700)
出处
《实用临床医药杂志》
2025年第2期80-85,共6页
Journal of Clinical Medicine in Practice
基金
2021年贵州省科教青年英才培训工程项目[黔省专合字(2021)513号]。
关键词
疏肝和胃方
胃食管反流病
过氧化物酶体增殖物激活受体
类视黄醇X受体
信号通路
liver-soothing and stomach-harmonizing recipe
gastroesophageal reflux disease
peroxisome proliferator-activated receptor
retinoid X receptor
signaling pathway
