PDGFRα^(+)细胞上P2Y1-SK3通路对功能性消化不良大鼠胃肠动力的调控机制  

Regulatory Mechanism of the P2Y1-SK3 Pathway on Gastrointestinal Motility in Functional Dyspepsia Rats with PDGFRα^(+) Cells

作　　者：杨德茜 陈琪 潘小丽 徐派的 Yang Deqian;Chen Qi;Pan Xiaoli(College of Acupuncture and Orthopedics,Hubei University of Chinese Medicine,Wuhan 430061,China;Yarin School of Nursing,Wuhan Institute Design and Sciences,Wuhan 430205,China)

机构地区：[1]湖北中医药大学针灸骨伤学院,武汉430061 [2]武汉设计工程学院亚心护理学院,武汉430205

出　　处：《华中科技大学学报（医学版）》2024年第5期599-607,共9页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2021CFB548)。

摘　　要：目的探究血小板衍生生长因子受体α^(+)(PDGFRα^(+))细胞上P2Y1-小电导Ca^(2+)激活K^(+)(SK3)通道对功能性消化不良(FD)大鼠胃肠动力的影响。方法将30只SD大鼠随机分为空白组、模型组、P2Y1受体抑制剂(MRS2500)组,每组10只。除空白组外,其余两组采用多因素干预法建立FD大鼠模型。造模成功后抑制剂组予以尾静脉注射P2Y1抑制剂MRS2500,其他组不采取干预措施。处理结束后进行行为学和胃肠动力学检测;用BL-420S生物信号系统采集并分析胃肠生物电信息;取胃窦组织评估病理变化;采用免疫印迹、实时荧光定量PCR技术检测各组大鼠胃窦PDGFRα、C-kit(卡介尔间质细胞特异性指标)、P2Y1和SK3的表达情况;采用免疫荧光法检测胃窦PDGFRα和C-kit、P2Y1、SK3的组织表达和共定位情况;用钙检测试剂盒检测胃窦组织中Ca^(2+)含量变化。结果FD模型建立后,大鼠活动度、体重增长速度和进食量都显著降低,胃肠动力减弱,胃窦内PDGFRα、C-kit、P2Y1和SK3表达水平降低。MRS2500干预后,P2Y1受体抑制剂组大鼠较模型组大鼠体重增长率和进食量升高,胃肠动力减弱情况改善,PDGFRα、P2Y1和SK3表达水平进一步降低,C-kit表达水平升高,Ca^(2+)含量降低。PDGFRα与C-kit在胃窦中不存在共表达,而PDGFRα与P2Y1、SK3共表达。结论长期的饮食和情绪失调会刺激肠神经系统释放抑制性神经递质,这一过程通过PDGFRα^(+)细胞上P2Y1受体引起SK3通道的Ca^(2+)敏感性降低,在多因素刺激诱导的FD模型大鼠胃肠动力障碍中起重要作用。Objective This study investigated the role of P2Y1-small conductance Ca^(2+)-activated K^(+)channel(SK3)channels in platelet-derived growth factor receptor-α-positive(PDGFRα^(+))cells in gastrointestinal motility in functional dyspepsia(FD).Methods Thirty rats were divided into control,model,and inhibitor groups(n=10 each group).The model and inhibitor groups were used to establish FD rat model,and the inhibitor group received MRS2500 via caudal injection.Behavioral and gastrointestinal assessments were conducted at the end of the experiment.Gastrointestinal electrophysiology was recorded,and gastric antrum samples were analyzed histopathologically.Western blotting and qPCR were used to measure PDGFRα,C-kit(a specificity indicator for interstitial cells of Cajal),P2Y1,and SK3 expression levels.Immunofluorescence staining was used to assess protein colocalization,and calcium assay kits were used to evaluate Ca^(2+)flux.Results Following model establishment,experimental rats presented reduced activity,weight gain,and food intake,accompanied by decreased gastrointestinal motility and decreased expression of PDGFRα,C-kit,P2Y1,and SK3 in the gastric antrum.After MRS2500 treatment,FD rats presented increased weight gain and food consumption,with improved gastrointestinal motility.The expression of PDGFRα,P2Y1,and SK3 continued to decrease,whereas C-kit expression and Ca^(2+)levels increased.Notably,there was no coexpression of PDGFRαwith C-kit,but significant coexpression of P2Y1 and SK3 was observed.Conclusion Stressors such as dietary factors and emotional distress may increase inhibitory neurotransmitter release in gastrointestinal tissues,leading to reduced Ca^(2+)sensitivity of the SK3 channel in PDGFRα^(+) cells,affecting gastrointestinal motility in FD.

关 键 词：功能性消化不良 血小板衍生生长因子受体α^(+)细胞 卡介尔间质细胞 P2Y1 小电导Ca^(2+)激活K^(+)通道 

分 类 号：R57[医药卫生—消化系统]