Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
目的明确低压低氧环境对大鼠肠道功能的影响特征,探讨缺氧诱导因子‐1α(HIF‐1α)及肠道菌群在其中的作用。方法将20只SPF级Wistar大鼠随机分为常氧对照组(NC组,n=10)和低压低氧模型组(HH组,n=10)。HH组采用低压低氧箱模拟海拔4000 m环...目的明确低压低氧环境对大鼠肠道功能的影响特征,探讨缺氧诱导因子‐1α(HIF‐1α)及肠道菌群在其中的作用。方法将20只SPF级Wistar大鼠随机分为常氧对照组(NC组,n=10)和低压低氧模型组(HH组,n=10)。HH组采用低压低氧箱模拟海拔4000 m环境,每日持续暴露10 h,连续干预28 d;NC组置于常氧环境同步饲养。干预第14天及28天检测大鼠1 h排便粒数及粪便含水量;采用腹部回撤反射(AWR)压力阈值评估肠道敏感性;通过糖水摄取量判断大鼠情绪状态;28天16S rRNA测序分析粪便菌群结构变化;Western blot法检测结肠组织HIF‐1α蛋白表达水平;酶联免疫吸附法检测血清炎症因子(IL‐6、TNF‐α、IL‐10)含量。结果与NC组相比,HH组大鼠第28天排便量(1.8±0.4 vs 3.6±0.5,粒)及含水量(22.4±4.0 vs 44.6±7.7,%)均明显降低(P均<0.001)。HH组AWR值(37.0±4.6 vs 30.0±3.5,mmHg)高于NC组(P=0.001),蔗糖水摄取量(10.0±1.8 vs 15.2±2.2,mL)低于NC组(P<0.001)。NC组大鼠结肠组织HIF‐1α蛋白表达低于HH组,HH组大鼠血清促炎因子IL‐6(165.6±18.3 vs 92.6±10.5,pg/mL)、TNF‐α(134.5±13.6 vs 85.3±9.7,pg/mL)含量显著高于NC组(P均<0.001);抗炎因子IL‐10(31.3±4.7 vs 56.5±6.4,pg/mL)显著低于NC组(P<0.001)。16S rRNA测序显示,HH组肠道菌群多样性显著降低,毛螺科NK4A136组相对丰度(0.035±0.044 vs 0.150±0.090)明显低于NC组(P=0.002);普雷沃氏菌科UCG‐001相对丰度(0.040±0.023 vs 0.010±0.003)明显高于NC组(P=0.001),两组大鼠显著富集物种差异明显。结论低压低氧环境可诱导大鼠出现便秘倾向、肠道敏感性降低及抑郁样行为,其机制可能与HIF‐1α异常激活导致的炎症反应引起肠道菌群失调相关。展开更多
This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the ...This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the phenotypes of bile acid dysregulation in IBS-D patients,and the related pathogenic molecular mechanisms.A primary focus is placed on dissecting the interaction mechanisms between the gut microbiota and bile acids,specifically the regulatory role of the gut microbiota in bile acid transformation and the influence of bile acids on the structure of the gut microbiota.Based on current research evidence,this article proposes the gut microbiota-bile acid axis as a potential therapeutic target for IBS-D.It aims to provide theoretical insights and novel perspectives for exploring innovative treatment strategies for IBS-D and elucidating its pathogenesis.展开更多
腹泻型肠易激综合征(Irritable Bowel Syndrome with Diarrhea,IBS-D)是一种常见的功能性胃肠病,以反复发作的腹痛、腹胀、腹泻为核心症状,常伴随焦虑、抑郁等心理问题。低FODMAP饮食通过限制难吸收碳水化合物,可减少肠道产气与刺激,有...腹泻型肠易激综合征(Irritable Bowel Syndrome with Diarrhea,IBS-D)是一种常见的功能性胃肠病,以反复发作的腹痛、腹胀、腹泻为核心症状,常伴随焦虑、抑郁等心理问题。低FODMAP饮食通过限制难吸收碳水化合物,可减少肠道产气与刺激,有效缓解IBS-D腹泻症状;微正念训练则能调节自主神经功能,减轻焦虑情绪,改善脑-肠轴失衡。COM-B模型(CaPability-OPPortunity-Motivation-Behavior)从能力、机会、动机三个维度解析行为改变机制,为多维度干预方案的构建提供了科学框架。本研究基于COM-B模型,整合微正念训练与低FODMAP饮食指导,构建协同干预方案,通过精准识别患者行为改变障碍,实现个性化干预,旨在为IBS-D患者提供更有效的非药物干预策略。现将效果分析如下。展开更多
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
文摘目的明确低压低氧环境对大鼠肠道功能的影响特征,探讨缺氧诱导因子‐1α(HIF‐1α)及肠道菌群在其中的作用。方法将20只SPF级Wistar大鼠随机分为常氧对照组(NC组,n=10)和低压低氧模型组(HH组,n=10)。HH组采用低压低氧箱模拟海拔4000 m环境,每日持续暴露10 h,连续干预28 d;NC组置于常氧环境同步饲养。干预第14天及28天检测大鼠1 h排便粒数及粪便含水量;采用腹部回撤反射(AWR)压力阈值评估肠道敏感性;通过糖水摄取量判断大鼠情绪状态;28天16S rRNA测序分析粪便菌群结构变化;Western blot法检测结肠组织HIF‐1α蛋白表达水平;酶联免疫吸附法检测血清炎症因子(IL‐6、TNF‐α、IL‐10)含量。结果与NC组相比,HH组大鼠第28天排便量(1.8±0.4 vs 3.6±0.5,粒)及含水量(22.4±4.0 vs 44.6±7.7,%)均明显降低(P均<0.001)。HH组AWR值(37.0±4.6 vs 30.0±3.5,mmHg)高于NC组(P=0.001),蔗糖水摄取量(10.0±1.8 vs 15.2±2.2,mL)低于NC组(P<0.001)。NC组大鼠结肠组织HIF‐1α蛋白表达低于HH组,HH组大鼠血清促炎因子IL‐6(165.6±18.3 vs 92.6±10.5,pg/mL)、TNF‐α(134.5±13.6 vs 85.3±9.7,pg/mL)含量显著高于NC组(P均<0.001);抗炎因子IL‐10(31.3±4.7 vs 56.5±6.4,pg/mL)显著低于NC组(P<0.001)。16S rRNA测序显示,HH组肠道菌群多样性显著降低,毛螺科NK4A136组相对丰度(0.035±0.044 vs 0.150±0.090)明显低于NC组(P=0.002);普雷沃氏菌科UCG‐001相对丰度(0.040±0.023 vs 0.010±0.003)明显高于NC组(P=0.001),两组大鼠显著富集物种差异明显。结论低压低氧环境可诱导大鼠出现便秘倾向、肠道敏感性降低及抑郁样行为,其机制可能与HIF‐1α异常激活导致的炎症反应引起肠道菌群失调相关。
文摘This article systematically reviews the characteristics of gut microbiota dysbiosis in IBS-D and associated therapeutic modulation strategies.It elaborates on the biosynthetic and metabolic pathways of bile acids,the phenotypes of bile acid dysregulation in IBS-D patients,and the related pathogenic molecular mechanisms.A primary focus is placed on dissecting the interaction mechanisms between the gut microbiota and bile acids,specifically the regulatory role of the gut microbiota in bile acid transformation and the influence of bile acids on the structure of the gut microbiota.Based on current research evidence,this article proposes the gut microbiota-bile acid axis as a potential therapeutic target for IBS-D.It aims to provide theoretical insights and novel perspectives for exploring innovative treatment strategies for IBS-D and elucidating its pathogenesis.
文摘腹泻型肠易激综合征(Irritable Bowel Syndrome with Diarrhea,IBS-D)是一种常见的功能性胃肠病,以反复发作的腹痛、腹胀、腹泻为核心症状,常伴随焦虑、抑郁等心理问题。低FODMAP饮食通过限制难吸收碳水化合物,可减少肠道产气与刺激,有效缓解IBS-D腹泻症状;微正念训练则能调节自主神经功能,减轻焦虑情绪,改善脑-肠轴失衡。COM-B模型(CaPability-OPPortunity-Motivation-Behavior)从能力、机会、动机三个维度解析行为改变机制,为多维度干预方案的构建提供了科学框架。本研究基于COM-B模型,整合微正念训练与低FODMAP饮食指导,构建协同干预方案,通过精准识别患者行为改变障碍,实现个性化干预,旨在为IBS-D患者提供更有效的非药物干预策略。现将效果分析如下。
