双果喉乐汤通过调控ERK1/2-COX-2-PGE2信号通路对急性咽炎模型大鼠的影响

Effect of Shuangguo Houle Tang on Rat Models with Acute Pharyngitis by Regulating ERK1/2-COX-2-PGE2 Signaling Pathway

目的:探讨双果喉乐汤改善急性咽炎大鼠的作用机制。方法:将60只大鼠随机分为对照组、模型组、地塞米松组、双果喉乐汤高、中、低剂量组,每组10只。除对照组外,其他各组大鼠建立急性咽炎模型。造模成功后,模型组、对照组灌胃等体积0.9%氯化钠溶液,地塞米松组、双果喉乐汤高、中、低剂量组分别灌胃相应剂量的药物,给药7 d。观察各组大鼠病理状态,检测各组大鼠血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)含量,咽部组织中丝裂原活化蛋白激酶(ERK1/2)和环氧合酶-2(COX-2)mRNA表达及ERK1/2、p-ERK1/2和COX-2蛋白的表达。结果:与对照组比较,模型组大鼠咽部组织细胞排序紊乱,黏膜上皮有严重角化,可见大量炎性细胞浸润,上皮层增生明显,黏膜内血管扩张及出血,腺体数量增多;血清中TNF-α、IL-1β、IL-6、PGE2含量、咽部组织中ERK1/2 mRNA和COX-2mRNA表达及咽部组织中p-ERK1/2和COX-2蛋白表达水平升高(P<0.05)。与模型组比较,地塞米松组、双果喉乐汤高、中、低剂量组大鼠血清中TNF-α、IL-1β、IL-6、PGE2含量、咽部组织中ERK1/2 mRNA和COX-2 m RNA表达及咽部组织中p-ERK1/2和COX-2蛋白表达水平降低(P<0.05)。与地塞米松组比较,双果喉乐汤中、低剂量组大鼠血清中TNF-α、IL-1β、IL-6、PGE2含量、咽部组织中ERK1/2 mRNA和COX-2 mRNA表达较高(P<0.05);双果喉乐汤低剂量组大鼠咽部组织中p-ERK1/2及COX-2蛋白表达水平较高(P<0.05);双果喉乐汤高剂量组大鼠血清中IL-1β、IL-6、PGE2含量及咽部组织中ERK1/2 mRNA表达较高(P<0.05),COX-2 m RNA表达较低(P<0.05)。与双果喉乐汤低剂量组比较,双果喉乐汤高、中剂量组大鼠血清中TNF-α、IL-1β、IL-6、PGE2含量及咽部组织中ERK1/2 mRNA和COX-2 mRNA表达较低(P<0.05);双果喉乐汤高剂量组大鼠咽部组织中p-ERK1/2及COX-2蛋白表达水平较低(P<0.05)。结论:双果喉乐汤对氨水诱发的大鼠急性咽炎具有明显的改善作用,可能与调节ERK1/2-COX-2-PGE2信号通路有关。

Objective:To discuss the improvement mechanism of Shuangguo Houle tang on rats with acute pharyngitis.Methods:A total of 60 rats were randomly divided into the control group,the model group,the dexamethasone group,the Shuangguo Houle tang groups with high dose,medium dose,and low dose,10 rats in each group.Except for the control group,rat models with acute pharyngitis were established in the other groups.After successful modeling,the model group and the control group were given gastric perfusion with same volume of normal saline;the Shuangguo Houle tang groups with high dose,medium dose,and low dose as well as the dexamethasone group were respectively treated with gastric perfusion with the corresponding dose of medicines for seven days.The pathological condition was observed in each group.The contents of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and prostaglandinE2(PGE2)were detected in each group.The expression levels of mRNA of ERK1/2 and COX-2 in the pharynx were detected in each group.The expression levels of protein of ERK1/2 and p-ERK1/2 in the pharynx were detected in each group.Results:In comparison with those of the control group,the pathological conditions of the model group were as following:disorderly arrangement of the pharynx cells,severe keratosis of mucosal epithelium,infiltration of massive inflammatory cells,significant proliferation of epithelial layer,vasodilatation and hemorrhage in mucosa,and the increased number of glands.When compared with those in the control group,in the model group,the contents of TNF-α,IL-1β,IL-6,and PGE2 in serum,the expression levels of m RNA of ERK1/2 and COX-2 in the pharynx,as well as the expression levels of protein of COX-2 and p-ERK1/2 in the pharynx were increased(P<0.05).When compared with those in the model group,in the dexamethasone group as well as the Shuangguo Houle tang groups with high dose,medium dose,and low dose,the contents of TNF-α,IL-1β,IL-6,and PGE2 in serum,the expression levels of mRNA of ERK1/2 and COX-2 in the pharynx,as well as the expression levels of protein of COX-2 and p-ERK1/2 in the pharynx were decreased(P<0.05).When compared with those in the dexamethasone group,the contents of TNF-α,IL-1β,IL-6,and PGE2 in serum,and the expression levels of mRNA of ERK1/2 and COX-2 in the pharynx in the Shuangguo Houle tang groups with medium dose and low dose were higher(P<0.05);the expression levels of protein of COX-2 and p-ERK1/2 in the pharynx in the Shuangguo Houle tang group with low dose were higher(P<0.05).When compared with those in the dexamethasone group,in the Shuangguo Houle tang group with high dose,the contents of IL-1β,IL-6,and PGE2 in serum,and the expression level of mRNA of ERK1/2 in the pharynx were higher(P<0.05),and the expression level of m RNA of COX-2 was lower(P<0.05).When compared with those in the Shuangguo Houle tang group with low dose,the contents of TNF-α,IL-1β,IL-6,and PGE2 in serum,and the expression levels of m RNA of ERK1/2 and COX-2 in the pharynx in the Shuangguo Houle tang groups with high dose and medium dose were lower(P<0.05);the expression levels of protein of p-ERK1/2 and COX-2 in the pharynx in the Shuangguo Houle tang group with high dose were lower(P<0.05).Conclusion:Shuangguo Houle tang has a significant improvement effect on rats with acute pharyngitis induced by ammonia water,which may be related to regulation of ERK1/2-COX-2-PGE2 signaling pathway.