越鞠丸干预CUMS小鼠对抑郁样行为、功能性消化不良及PACAP/PAC1-R表达的影响

Effects of Yueju Pill on Depressive Behavior, Functional Dyspepsia and PACAP/PAC1-R Expression in CUMS Mice

目的探讨越鞠丸对抑郁共病功能性消化不良小鼠抑郁样行为和胃肠功能的影响。方法将C57BL/6J小鼠随机分为对照组、模型组、越鞠丸低剂量组、越鞠丸高剂量组和阳性药组,采用慢性不可预知温和应激(CUMS)构建共病模型,通过行为学检测、尼氏染色评估小鼠抑郁样行为和神经元损伤;胃肠组织病理、胃排空率、小肠推进率评估胃肠功能;ELISA法检测PACAP、VIP、IL-6、TNF-α、BDNF表达;Western blot检测PAC1-R、Vipr1、Vipr2蛋白表达。结果模型组小鼠表现出抑郁样行为,海马尼氏体数量减少,胃肠运动减慢,血清炎症因子IL-6、TNF-α水平升高(P<0.05,P<0.01),PACAP、VIP、BDNF表达降低(P<0.05,P<0.01),海马、胃窦、十二指肠组织PAC1-R、Vipr1、Vipr2表达降低(P<0.05,P<0.01)。与模型组比较,越鞠丸低、高剂量组可改善除Vipr1、Vipr2之外的其他上述指标(P<0.05,P<0.01)。结论越鞠丸可通过PACAP/PAC1-R降低炎症因子,升高BDNF水平,改善CUMS小鼠抑郁样行为和功能性消化不良。

OBJECTIVE To explore the effects of Yueju Pill on depression and gastrointestinal function in depressed co-morbid functional dyspepsia mice.METHODS C57BL/6J mice were randomly divided into control group,model group,Yueju Pill low-dose group,Yueju Pill high-dose group and positive drug group.A co-morbidity model was constructed using chronic unpredictable mild stress(CUMS),and the mice were assessed for depression-like behaviour and neuronal damage by behavioural tests and Nissl staining;gastrointestinal function was assessed by HE staining of gastric and intestinal tissues,gastric emptying rate,and small intestinal propulsive rate;PACAP,VIP,IL-6,TNF-α,and BDNF expression were detected by ELISA;PAC1-R,Vipr1,and Vipr2 protein expression were detected by protein immunoblotting.RESULTS Mice in the model group showed depression-like behaviour,reduced number of hippocampal nidus,slowed gastrointestinal motility,elevated serum inflammatory factors IL-6 and TNF-α(P<0.05,P<0.01),and reduced expression of PACAP,VIP,and BDNF(P<0.05,P<0.01),The PAC1-R,VPAC1-R,VPAC2-R expression decreased in the hippocampus and gastric sinus,duodenal tissue(P<0.05,P<0.01).Compared with the model group,the low and high dose groups of Yueju Pill improved the above indexes except for Vipr1 and Vipr2(P<0.05,P<0.01).CONCLUSION Yueju Pill can reduce inflammatory factors through PACAP/PAC1-R,increase the level of BDNF,and improve the depression-like behaviour and gastrointestinal dysfunction in CUMS mice.