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作 者:万建华 孙登龙 余婧婷 程小英 詹扬 李颖萌 刘文君 WAN Jian-hua;SUN Deng-long;YU Jing-ting;CHENG Xiao-ying;ZHAN Yang;LI Ying-meng;LIU Wen-jun(Department of Research and Development,Jiangzhong Pharmaceutical Stock Co.,Ltd.,Nanchang 330029)
机构地区:[1]江中药业股份有限公司研发部,南昌330029
出 处:《中南药学》2024年第9期2286-2291,共6页Central South Pharmacy
摘 要:目的利用蛋白组学技术研究健胃消食片对小儿厌食的改善作用及作用机制。方法采用3周龄SD大鼠,除对照组外均采用高脂高蛋白饮食4周造模,造模成功后随机分为模型组,多潘立酮(10 mg·kg^(-1))组、健胃消食片2 g·kg^(-1)组和健胃消食片5 g·kg^(-1)组,给药1周,给药结束后检测大鼠体重和胃肠动力指标,并取血和胃部组织分别进行血浆激素水平检测和蛋白组学分析。结果口服健胃消食片使得小儿厌食模型大鼠的摄食量和胃肠动力显著提高,同时血浆胃动素(MTL)和β-内啡肽(β-EP)水平升高,生长抑制素(SST)水平下降;蛋白组学分析发现小儿厌食模型大鼠的发病过程以及健胃消食片的治疗过程与多个蛋白的差异表达有关,其中的胰蛋白酶原2(Prss2蛋白),主要参与消化及蛋白质的吸收;Ndufb2参与了内源性大麻素信号传导,在激活的状态下对摄食具有促进作用,这两种蛋白在模型诱导过程中下调,但在健胃消食片灌胃之后表达上调。同时多个信号通路参与到了健胃消食片的治疗,其中肌动蛋白细胞骨架的调节通路在治疗之后显著富集于胃组织,此通路具有促进胃肠平滑肌收缩的作用。结论健胃消食片通过增加小儿厌食模型大鼠的摄食量和胃肠动力改善厌食情况,调节MTL、β-EP和SST的分泌;Prss2和Ndufb2两个蛋白以及肌动蛋白细胞骨架调节通路不仅参与了小儿厌食的发病过程,同时也参与了健胃消食片对小儿厌食的治疗过程,推测可能是健胃消食片发挥治疗作用的重要靶点。Objective To determine the improvement effect and mechanism of Jianwei Xiaoshi tablets on infantile anorexia by proteomics.Methods 3-week-old SD rats were randomly divided into 5 groups after 4 weeks of high-fat and high-protein diet modeling:a control group,a model group,a domperidone 10 mg·kg^(-1 )group,a Jianwei Xiaoshi tablets 2 g·kg^(-1 )group and a Jianwei Xiaoshi tablets 5 g·kg^(-1 )group.After one-week administration,the body weight and gastrointestinal motility indicators of the rats were measured,and the blood and gastric tissues were collected for plasma hormone levels and proteomics analysis,respectively.Results Oral administration of Jianwei Xiaoshi tablets significantly increased the food intake and gastrointestinal motility in rats with infantile anorexia.While the plasma motilin(MTL)andβ-endorphin(β-EP)increased,the level of somatostatin(SST)decreased.Proteomic analysis revealed that the pathogenesis of infantile anorexia model rats,as well as the therapeutic process of Jianwei Xiaoshi tablets,was associated with differential expression of several proteins.Among these proteins,trypsinogen 2(Prss2)played a key role in digestion and protein absorption.Additionally,Ndufb2 was involved in endogenous cannabinoid signaling,facilitating ingestion in the activated state.During the model induction,the expression of both proteins was down-regulated,but after gavage with Jianwei Xiaoshi tablets,their expression was up-regulated.Furthermore,several signaling pathways might involved in the treatment with Jianwei Xiaoshi tablets.Notably,the regulatory pathway of actin cytoskeleton was obviously enriched in the gastric tissues after the treatment.This pathway promoted the contraction of the gastrointestinal smooth muscle.Conclusion Jianwei Xiaoshi tablets may improve infantile anorexia by increasing food intake and gastrointestinal motility,regulating the secretion of MTL,β-EP,and SST in infantile anorexic rats.Prss2 and Ndufb2 proteins,along with the actin cytoskeleton regulatory pathway,not only are invo
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