【摘要】 目的 探讨熊菊复方颗粒对急性咽炎伴发热大鼠的解热抗炎作用及机制。方法 采用合煎醇沉提取、β-环糊精包合工艺制备熊菊复方颗粒。将SD大鼠随机分为正常组、模型组、咽立爽+对乙酰氨基酚组(阳性药对照组，0.018+0.045 g·kg^-1)及熊菊复方颗粒低、高剂量组(0.54、1.08 g·kg^-1)；通过辣椒素结合脂多糖（LPS）诱导急性咽炎伴发热大鼠模型；造模后立即灌胃相应药物。大鼠造模给药后每0.5 h测体温1次，持续监测9 h，计算体温变化值（△T）；采用ELISA法检测大鼠血清前列腺素E2（PGE2）含量；HE染色法观察大鼠咽部组织病理变化；qPCR法检测咽部组织炎症[肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1β、IL-10]及瞬时受体电位（TRP）通道相关基因的表达水平；免疫荧光法检测咽部组织TRPV1蛋白表达水平；免疫组化法检测咽部组织TRPM8蛋白表达水平。结果 模型组大鼠注射LPS后0.5 h，体温升高1.03℃，造模成功；熊菊复方颗粒低、高剂量组大鼠各时间点△T均低于模型组。与正常组比较，模型组大鼠的血清PGE2水平显著升高（P<0.01）；咽部组织黏膜层中固有层明显增厚，下层腺体膨大，与固有层分界不清；咽部组织TNF-α、IL-6、IL-1β、TRPV1 mRNA表达水平显著升高（P<0.01）,IL-10、TRPM8 mRNA表达水平明显降低（P<0.05）,TRPV1蛋白表达显著上调（P<0.01）,TRPM8蛋白表达显著下调（P<0.01）。与模型组比较，各给药组大鼠的血清PGE2水平显著降低（P<0.01）；咽部组织病理损伤均有所改善，固有层厚度降低，部分腺体形态恢复正常；咽部组织TNF-α、IL-6、IL-1β、TRPV1 mRNA表达水平显著降低（P<0.01）,IL-10、TRPM8mRNA表达水平显著升高（P<0.01）,TRPV1蛋白表达显著下调（P<0.01）,TRPM8蛋白表达显著上调（P<0.05,P<0.01）。结论 熊菊复方颗粒对辣椒素结合LPS诱导急性咽炎伴发热大鼠具有明显的解热作用，并能抑制咽部组织炎症，改善病理损伤，具有防治急性咽炎的作用，其作用机制可能与TRP通道有关。更多还原

【Abstract】 Objective To investigate the antipyretic and anti-inflammatory effects of Xiongju Compound Granules on rats with acute pharyngitis accompanied by fever and elucidate the underlying mechanisms. Methods Xiongju Compound Granules were prepared using combined decoction with ethanol precipitation followed by β-cyclodextrin inclusion. SD rats were randomly divided into a normal group, a model group, a Yanlishuang + Paracetamol group(positive drug control,0.018 + 0.045 g·kg^-1),and low-dose and high-dose Xiongju Compound Granules groups(0.54 and 1.08 g·kg^-1). An acute pharyngitis with fever rat model was induced using capsaicin combined with lipopolysaccharide（LPS）. The corresponding drugs were administered immediately via intragastric gavage after model establishment. Body temperature was measured every 0.5 hours for 9 hours post-administration to calculate the change in body temperature （△T）. Serum prostaglandin E2（PGE2） levels were measured using ELISA. Pharyngeal tissue histopathological changes were observed using HE staining. The expression levels of inflammatory cytokines [tumor necrosis factor（TNF）-α,interleukin（IL）-6,IL-1β,IL-10] and transient receptor potential（TRP） channel-related genes in pharyngeal tissue were detected using qPCR. TRPV1 protein expression in pharyngeal tissue was detected using immunofluorescence,and TRPM8 protein expression was detected using immunohistochemistry. Results In the model group,body temperature increased by 1.03 ℃ at 0.5 hours post-LPS injection,indicating successful model establishment. The △T at various time points in both the low-dose and high-dose Xiongju Compound Granules groups was lower than that in the model group. Compared with the normal group, the model group exhibited significantly elevated serum PGE2 levels（P<0.01）;marked thickening of the lamina propria in the pharyngeal mucosal layer,with swollen glands in the submucosa and an indistinct boundary with the lamina propria;significantly increased mRNA expression levels of TNF-α,IL-6,IL-1β,and TRPV1 in pharyngeal tissue（P<0.01）;significantly decreased mRNA expression levels of IL-10 and TRPM8（P<0.05）;significantly upregulated TRPV1 protein expression（P<0.01）;and significantly downregulated TRPM8 protein expression（P<0.01）. Compared with the model group, all treatment groups showed significantly decreased serum PGE2 levels（P<0.01）;improved pharyngeal histopathological damage,characterized by reduced lamina propria thickness and partial restoration of normal glandular morphology; significantly decreased mRNA expression levels of TNF-α, IL-6, IL-1β, and TRPV1 in pharyngeal tissue（P<0.01）; significantly increased mRNA expression levels of IL-10 and TRPM8（P<0.01）;significantly downregulated TRPV1 protein expression（P<0.01）;and significantly upregulated TRPM8 protein expression（P<0.05,P<0.01）. Conclusion Xiongju Compound Granules exhibit significant antipyretic effects in rats with acute pharyngitis accompanied by fever induced by capsaicin combined with LPS, inhibit pharyngeal inflammation, and ameliorate histopathological damage, thereby exerting a therapeutic effect against acute pharyngitis. The underlying mechanism may involve modulation of TRP channels.更多还原