小半夏汤对1-PBG和P物质致异食癖大鼠脑干Fos蛋白表达的影响

Effect of Xiaobanxia Decoction on Fos Protein Expression in the Brainstem in 1-PBG and Substance P Induced Pica in Rats

目的:从5-HT3受体和NK1受体角度探讨小半夏汤防治化疗性恶心呕吐机制。方法:Wistar大鼠随机分为正常对照组、小半夏汤正常对照组、5-HT3受体激动剂1-phenylbiguanide(1-PBG)模型组、阳性药昂丹司琼2. 6 mg/kg组和小半夏汤0. 8 g/kg组、1. 6g/kg组、3. 2g/kg组;NK1受体激动剂P物质(SP)模型组及阳性药阿瑞吡坦11. 1mg/kg组和小半夏汤0. 8g/kg组、1. 6g/kg组、3. 2 g/kg组。分别注射1-PBG 25 mg/kg、SP 250 ng/kg建立两种大鼠异食癖模型。各组动物在造模前3天开始灌胃给药,直至造模后72 h。每24 h称量并计算摄食高岭土量。造模后24 h和72 h分两批处理动物,取脑,免疫组化法观察各组动物脑干最后区(area postrema,AP)和孤束核(Nucleus of solitary tract,NTS) Fos蛋白表达情况。结果:1-PBG和SP均可使大鼠摄食高岭土量增加,其中1-PBG造模后24 h,模型大鼠摄食高岭土量出现峰值;SP造模后72 h摄食高岭土量出现峰值,造模后48 h是次峰值。与模型组比较,小半夏汤各剂量治疗组及两种阳性药治疗组均可明显抑制模型大鼠摄食高岭土。造模后24 h和72 h,与空白组比较,模型组大鼠脑干AP和NTS的Fos蛋白表达均明显上调;小半夏汤各剂量组和阳性药组均能显著下调模型动物脑干AP和NTS的Fos蛋白表达。结论:小半夏汤可以拮抗5-HT3受体激动剂和NK1受体激动剂所致的大鼠异食癖、降低呕吐反射相关脑区的Fos蛋白表达,提示小半夏汤防治化疗性恶心呕吐作用与阻断5-HT3受体和NK1受体有关。

Objective: To investigate the mechanisms of Xiao-Ban-Xia Decotion (XBXD) on the role of 5-HT3 Receptor and NK1 Receptor in the prevention and treatment of chemotherapy-induced nausea and vomiting. Methods: Wistar rats were randomly divided into the normal control groups,XBXD normal control group,5 HT3 receptor agonist 1-PBG model group,2. 6 mg/kg ondansetron group,XBXD 1-PBG groups (0.8 g/kg,1. 6 g/kg,3. 2 g/kg),SP model group,11. 1 mg/kg aprepitant group and SP-XBXD groups (0. 8 g/kg,1. 6 g/kg,3. 2 g/kg). Rat pica models were established by intraperitoneal injection of 25 mg/kg 1-PBG or 250 ng/kg Substance P (SP) respectively. Drugs were orally given from 3 days before modeling to 72 h after model establishment. Kaolin consumption was weighed every 24 hours. Rats in each group were sacrificed for brain tissue detachment at the time points of 24 h and 72 h after modeled. Fos positive cells counts in area postrema (AP)and Nucleus of solitary tract (NTS) of brainstem were detected by immunohistochemisty method. Results: Kaolin consumptions in 1-PBG and SP model groups were significantly increased,the peak appeared at 24 h and 72 h respectively. Compared with the model group,all doses of XBXD and the positive drug significantly inhibited kaolin consumptions in 1-PBG or SP-treated rats. Compared with the control group,24 h and 72 h after modeled,Fos protein expression levels in AP and NTS of rats brainstem were obviously increased in the model group,all doses of XBXD and the positive drug significantly reduced Fos protein expression levels. Conclusion: XBXD can improve the selective agonist induced pica of rats and reduce Fos protein expression of AP and NTS,which may be related to the inhibition of 5-HT3 receptor and NK1 receptor. This may be one of main mechanisms of XBXD on the prevention and treatment of CINV.