半夏泻心汤对功能性消化不良大鼠抑郁状态及促肾上腺皮质激素释放因子相关通路的影响  

Effects of Banxia Xiexin decoction on depressive state and CRF-related pathways in rats with functional dyspepsia

作　　者：耿琦[1] 李敬伟[1] 凌江红 蒋健[1] GENG Qi;LI Jingwei;LING Jianghong;JIANG Jian(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)

机构地区：[1]上海中医药大学附属曙光医院消化内科,上海200021

出　　处：《陕西中医》2024年第2期147-152,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82174309);国家中医药管理局中医药传承与创新“百千万”人才工程(岐黄工程)岐黄学者项目[国中医药办人教函(2019)62号];国家中医药管理局全国名老中医药专家传承工作室建设项目“蒋健全国名老中医药专家传承工作室”[国中医药人教函(2022)75号];上海市卫生和计划生育委员会上海市名老中医学术经验研究工作室建设项目(SHGZS-2017024)。

摘　　要：目的:观察半夏泻心汤对功能性消化不良(FD)大鼠抑郁样行为、下丘脑促肾上腺皮质激素释放因子(CRF)及其受体CRF-R1、CRF-R2的影响。方法:48只SPF级Wistar大鼠随机分为空白组、模型组、氟西汀组、半夏泻心汤低、中、高剂量组,共六组,每组各8只。空白组正常饲养,其余五组采用不规则喂养+夹尾激惹刺激法造模,造模成功后半夏泻心汤低、中、高各剂量组分别给予0.62、1.24、2.48 g/ml剂量灌胃,氟西汀组给予2 mg/kg氟西汀,空白组及模型组均给予同等容积的蒸馏水,各组连续灌胃14 d。干预结束后采用糖水偏好实验和旷场实验测试各组抑郁样行为;HE染色观察大鼠胃窦组织基本形态;RT-qPCR和Western blot检测大鼠下丘脑中CRF、CRF-R1和CRF-R2 mRNA和蛋白的表达。结果:与空白组比较,模型组大鼠体重、糖水偏好度、旷场实验移动总距离和直立次数均明显下降(P<0.05);下丘脑中CRF、CRF-R1 mRNA和蛋白表达均明显升高(P<0.01),CRF-R2 mRNA和蛋白的表达均明显降低(P<0.01)。与模型组比较,半夏泻心汤各剂量组大鼠的体重、糖水偏好度、旷场实验移动总距离和直立次数均明显增加(P<0.05);半夏泻心汤各剂量组FD大鼠下丘脑中CRF、CRF-R1 mRNA的表达量均明显降低(P<0.01),CRF-R2 mRNA的表达明显升高;半夏泻心汤高剂量组FD大鼠下丘脑中CRF蛋白表达均明显降低(P<0.01),半夏泻心汤各剂量组FD大鼠下丘脑中CRF-R1蛋白表达明显降低(P<0.01),CRF-R2蛋白表达升高(P<0.05)。结论:半夏泻心汤可通过调控CRF通路,恢复CRF-R1和CRF-R2的平衡状态,发挥抗抑郁的作用。Objective:To observe the effects of Banxia Xiexin decoction on depression-like behavior,hypothalamic corticotrophin releasing factor(CRF),CRF-R1 and CRF-R2 in functional dyspepsia(FD) rats.Methods:A total of 48 SPF Wistar rats were randomly divided into blank group,model group,fluoxetine group,Banxia Xiexin decoction low-dose,medium-dose and high-dose groups,with 8 rats in each group.The blank group was fed normally,and the other 5 groups were treated with irregular feeding + clip-tail stimulation.After successful modeling,Banxia Xiexin decoction low,medium and high dose groups were given 0.62 g/ml,1.24 g/ml and 2.48 g/ml dose gavage,respectively,fluoxetine group was given 2 mg/kg fluoxetine,blank group and model group were given the same volume of distilled water.Each group was given continuous gavage for 14 days.After the intervention,the depression-like behavior was observed by sugar water preference experiment and open field experiment.The gastric antrum tissue was observed by HE staining.The mRNA and protein expressions of CRF,CRF-R1 and CRF-R2 in the hypothalamus of rats were detected by qPCR and Western blot.Results:Compared with the blank group,the body weight,sugar and water preference,the total distance of open field experiment and the number of upright times of rats in the model group decreased significantly.The mRNA and protein expressions of CRF and CRF-R1 in hypothalamus were significantly increased(P<0.01),while the mRNA and protein expressions of CRF-R2 were significantly decreased(P<0.01).Compared with model group,the body weight,sugar and water preference,the total distance of moving in open field and the number of upright times of rats in Banxia Xiexin decoction groups were significantly increased(P<0.05).The mRNA expressions of CRF and CRF-R1 in hypothalamus of FD rats in Banxia Xiexin decoction groups were significantly decreased(P<0.01),while the mRNA expression of CRF-R2 was significantly increased.The expression of CRF protein in hypothalamus of FD rats in Banxia Xiexin decoction high-dose

关 键 词：功能性消化不良 半夏泻心汤 抑郁状态 糖水偏好实验 旷场实验 促肾上腺皮质激素释放因子通路 

分 类 号：R256.3[医药卫生—中医内科学]