经典复方防治化疗性恶心呕吐大鼠的作用及机制研究

Effects of Traditional Chinese Medicine Formulas on Prevention and Treatment of Chem-otherapy-induced Nausea and Vomiting in Rats and Its Mechanisms

目的探讨经典复方橘皮竹茹汤、丁香柿蒂汤、四君子汤对顺铂诱导的化疗性恶心呕吐(chemotherapy-induced nausea and vomiting,CINV)大鼠的作用及初步机制。方法48只雄性Wistar大鼠随机分为空白对照组、模型组、昂丹司琼组(2.6 mg·kg^(-1))、橘皮竹茹汤组(10.8 g·kg^(-1))、丁香柿蒂汤组(4.3 g·kg^(-1))和四君子汤组(5.9 g·kg^(-1)),每组8只。首次给药1 h后空白对照组腹腔注射等量生理盐水,其余各组腹腔注射顺铂6 mg·kg^(-1)建立大鼠CINV模型,造模后各组给予相应药物干预,每日2次,连续7次。期间每24 h进行体质量、摄食量和高岭土摄入量的监测。给药结束后比较各组动物的胃残留率和小肠推进率,观察胃窦、回肠组织的病理变化,采用ELISA法检测血清、延髓和回肠的5-HT含量。结果与空白对照组比较,模型组大鼠体重、摄食量显著降低、高岭土摄入量显著增加(P<0.05,P<0.01),胃残留率升高(P<0.01),小肠推进率下降(P<0.01),延髓和回肠5-HT含量升高(P<0.05,P<0.01);与模型组比较,橘皮竹茹汤和丁香柿蒂汤能显著增加体重和摄食量,降低胃残留率(P<0.01),增加小肠推进率(P<0.01),其中橘皮竹茹汤对延髓和回肠5-HT含量的降低作用更明显(P<0.01),四君子汤和橘皮竹茹汤对高岭土摄入具有较明显的抑制作用。结论三种经典复方对化疗性恶心呕吐大鼠均有改善作用,其中橘皮竹茹汤对体重、摄食量及恶心呕吐的综合改善作用较好,其机制可能与促进胃肠动力的恢复及抑制5-HT介导的呕吐中枢有关。

Objective To explore the effects of Jupi Zhuru decoction,Dingxiang Shidi decoction,Sijunzi decoction on chemother-apy-induced nausea and vomiting induced by cisplatin in rats.Methods 48 male Wistar rats were randomly divided into blank control group,model group,ondansetron group(2.6 mg·kg^(-1)),Jupi Zhuru decoction group(10.8 g·kg^(-1)),Dingxiang Shidi decoction group(4.3 g·kg^(-1))and Sijunzi decoction group(5.9 g·kg^(-1))(n=8).The CINV model of rats were established by single intraperitoneal injection of 6 mg·kg^(-1)cisplatin while the blank control with the saline one hour after the first treatment,then continued administration by twice daily for 7 times.Body weight,food intake and kaolin intake of all rats were monitored ev-ery 24 h.The gastric residual rate and small intestine propulsion rate of each group were compared,and the pathological changes of gastric antrum and ileum were observed.The contents of 5-HT in serum,medulla oblongata and ileum were measured by ELISA.Results Compared with the blank control group,body weight,food intake were significantly decreased and kaolin intake increased in model groups(P<0.05,P<0.01),gastric residual rate was increased(P<0.01),small intestine propulsion rate was decreased(P<0.01),the contents of 5-HT in medulla oblongata and ileum were increased(P<0.05,P<0.01).Com-pared with the model group,Jupi Zhuru decoction and Dingxiang Shidi decoction significantly increased body weight and food in-take,decreased the gastric residual rate(P<0.01)and increased the small intestine propulsion rate(P<0.01),among which Jupi Zhuru decoction had the obvious effect on the reduction of 5-HT contents in medulla oblongata and ileum(P<0.01).Si-junzi decoction and Jupi Zhuru decoction significantly reduced the intake of kaolin.Conclusion The three classic TCM formulas can ameliorate the nausea and vomiting induced by chemotherapy drugs,among which Jupi Zhuru decoction has a better compre-hensive regulation effect on body weight,food intake and nausea-vomiting.The possible mechanism is related to promoting the recovery of gastrointestinal motility and inhibiting 5-HT mediated vomiting center.