连翘防治化疗性恶心呕吐及其抗炎活性研究

Study of Forsythia Suspensa on Chemotherapy-Induced Nausea and Vomiting and Its Anti-Inflammatory Activity

目的:采用化疗性大鼠异食癖模型,从抗炎角度探讨连翘防治化疗性恶心呕吐的作用机制,并初步探讨炎症与呕吐的关系。方法:取Wistar雄性大鼠随机分为正常对照组、连翘3. 5 g/kg正常对照组、顺铂模型组、地塞米松0. 94 mg/kg治疗组、连翘3. 5 g/kg治疗组。各组灌胃相应药物或蒸馏水,每天给药2次,连续给药6 d。给药第3 d第1次灌胃后1 h,除正常对照组和连翘正常对照组腹腔注射等容积生理盐水外,其余各组均腹腔注射顺铂6 mg/kg建立大鼠化疗性异食癖模型。计算各组大鼠造模后72 h高岭土摄入总量;ELISA法检测血清中TNF-ɑ、IL-1β、PGE2含量;HE法观察大鼠胃窦及回肠组织病理学改变,并测量胃黏膜厚度和小肠绒毛高度,免疫组化法检测胃窦和回肠组织COX-2及NF-κB p65阳性表达。结果:模型组大鼠摄食高岭土量显著高于正常对照组,造模后72 h,模型组大鼠胃肠黏膜可见炎性病理改变,胃黏膜厚度及小肠绒毛高度均显著降低,血清中TNF-ɑ、IL-1β、PGE2水平均显著升高,胃窦和回肠组织中NF-κB p65、COX-2阳性表达均显著上调。连翘3. 5 g/kg可显著抑制化疗大鼠摄食高岭土,改善胃肠黏膜病理损伤,降低化疗大鼠血清中TNF-ɑ、IL-1β、PGE2等炎症因子水平,下调胃窦及回肠组织中NF-κB p65及胃窦COX-2阳性表达。结论:连翘可显著改善顺铂导致的大鼠异食癖行为,具有防治化疗性恶心呕吐作用,该作用与其抗炎作用有关。

Objective: To explore the mechanism of Forsythia suspensa on preventing and treating chemotherapy-induced nausea and vomiting (CINV) from the perspective of its anti-inflammation. Methods: Wistar male rats were randomly divided into the normal control group,3. 5 g/kg Forsythia suspensa control group,cisplatin model group,0. 94 mg/kg dexamethasone group and 3. 5 g/kg Forsythia suspensa treatment group. Corresponding drugs or saline water was given twice a day for 6 days. One hour after 3 rd day administration,saline water was intraperitoneally injected to the normal control group and Forsythia suspensa control group,6 mg/kg cisplatin was intraperitoneally injected to the other groups,to establish the pica model. The total kaolin intake was calculated 72 h after modeled. The contents of TNF-α,IL-1β and PGE2 in serum were detected by ELISA. The pathological changes of gastric antrum and ileum were observed by HE staining,the thickness of gastric mucosa and the height of small intestinal villi were measured. The positive expressions of COX-2 and NF-κB p65 in gastric antrum and ileum was detected by immunohistochemical method. Results: The amount of kaolin intake in the model group was significantly increased. 72 hours after cisplatin injection,inflammatory pathological changes were observed in gastrointestinal mucosa of rats in model group. The thickness of gastrointestinal mucosa and the height of small intestinal villi were significantly reduced. The levels of TNF-α,IL-1β and PGE2 in serum were significantly increased. The positive expressions of NF-κB p65 and COX-2 in gastric antrum and ileum were also significantly up regulated. 3. 5 g/kg Forsythia suspensa significantly inhibited the ingestion of kaolin and improved the pathological damage of gastrointestinal mucosa in rats treated with cisplatin,it significantly reduced the serum levels of inflammatory factors such as TNF-α,IL-1β and PGE2,and reduced the positive expressions of NF-κB p65 and COX-2 in gastric antrum and ileum. Conclusion: Forsythia suspensa can significantly inhibit rat pica behavior induced by cisplatin,suggesting that it has the potential to treat CINV,which is related to its anti-inflammatory effect.