孕期应激诱发子代成年大鼠内脏痛高敏的分子神经机制分析-molecular neural mechanism analysis of visceral pain hypersensitivity induced by stress during pregnancy in offspring of adult rats.docxVIP

孕期应激诱发子代成年大鼠内脏痛高敏的分子神经机制研究英文摘要Neuronal and Molecular mechanisms of visceral hypersensitivity in adult rat offspring induced by prenatal maternal stressAbstractBackground Aims: Irritable bowel syndrome (IBS) ，is a disorder of unknown etiology，is characterized by widespread, and chronic abdominal pain associated with altered bowel movements. An increasing body of evidence indicates that stressorspresented during gestational periods could have long-term effects on the offspring’s tissure structure and function, which may perdispose to gastrointestinal diseases. The aim of the present study is designed to determine whether maternal psychological stress is a prenatanl factor affecting gastrointestinal sensitivity and to investigate possible mechanisms underlying prenatal maternal stress (PMS)-induced visceral hyperalgesia in adult male rat offspring.Methods: Pregnant Sprague Dawley rats were exposed to heterotypic intermittent stress from gestational day 6 to 22. Visceral motor responses to colorectal distension (CRD) were determined by recording electromyogram of abdominal external oblique muscles in adult male offspring. DiI was injected into the colon wall to label colon-specific thoracolumbar T13-L2 DRG neurons. Neuronal excitability was examined by patch clamp techniques. AOAA, an antagonist of the endogenous hydrogen sulfide producing enzyme cystathionine-β-synthase (CBS) was used intraperitoneally. The expression levels of CBS andtransientreceptorpotentialvanilloid1(TRPV1)proteinincolon-specific thoracolumbar (T13-L2) DRGs were analyzed by western blotting. H2S levels in blood samples were measured with spectrophotometry.Results: PMS significantly increased visceromoter response to colorectal distension in adult male offspring rats from 6 weeks to 10 weeks. PMS also enhanced the neuronal excitability by depolarizing resting membrane potentials, lowering rheobase and increasing the number of action potentials evoked by 2X and 3X rhe