Butyrate inhibits visceral allodynia and colonic hyperpermeability in rat models of irritable bowel syndrome
Butyrate inhibits visceral allodynia and colonic hyperpermeability in rat models of irritable bowel syndrome
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DOI：
10.1038/s41598-019-56132-4
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发表时间：
2019-12
影响因子：
4.6
通讯作者：
T. Nozu;Saori Miyagishi;Rintaro Nozu;K. Takakusaki;T. Okumura
中科院分区：
文献类型：
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作者：
T. Nozu;Saori Miyagishi;Rintaro Nozu;K. Takakusaki;T. Okumura
脂多糖（LPS）或重复避水应激（WAS）通过促肾上腺皮质激素释放因子（CRF）和促炎细胞因子诱导内脏异常性疼痛和肠道高通透性，建立大鼠肠易激综合征（IBS）模型。由于已知丁酸盐抑制促炎细胞因子的释放，我们假设丁酸盐在IBS模型中使这些结肠变化恶化。内脏痛通过电生理学测量对结肠扩张的反应的腹肌收缩阈值来评估。通过测量结肠组织中伊文思蓝的吸光度来确定结肠通透性。连续3天结肠滴注丁酸钠（SB; 0.37 - 2.9 mg/kg）可剂量依赖性地抑制LPS（1 mg/kg）诱导的内脏异常性疼痛和结肠通透性过高。SB可阻断WAS（1 h，3 d）或CRF（50 μg/kg）引起的内脏改变。SB在LPS模型中的这些作用可被AMPK抑制剂化合物C、PPAR-γ拮抗剂GW 9662、NO合成抑制剂NG-硝基-L-精氨酸甲酯、纳洛酮或舒必利消除。SB在IBS动物模型中减轻内脏异常性疼痛和结肠通透性过高。这些作用可能是AMPK和PPAR-γ依赖的，也可能是通过NO、阿片和中枢多巴胺D2通路介导的。丁酸盐可能是治疗IBS的有效药物。
Lipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral allodynia and gut hyperpermeabilityviacorticotropin-releasing factor (CRF) and proinflammatory cytokines, which is a rat irritable bowel syndrome (IBS) model. As butyrate is known to suppress the release of proinflammatory cytokine, we hypothesized that butyrate alleviates these colonic changes in IBS models. The visceral pain was assessed by electrophysiologically measuring the threshold of abdominal muscle contractions in response to colonic distention. Colonic permeability was determined by measuring the absorbance of Evans blue in colonic tissue. Colonic instillation of sodium butyrate (SB; 0.37−2.9 mg/kg) for 3 days inhibited LPS (1 mg/kg)-induced visceral allodynia and colonic hyperpermeability dose-dependently. Additionally, the visceral changes induced by repeated WAS (1 h for 3 days) or CRF (50 µg/kg) were also blocked by SB. These effects of SB in the LPS model were eliminated by compound C, an AMPK inhibitor, or GW9662, a PPAR-γ antagonist, NG-nitro-L-arginine methyl ester, a NO synthesis inhibitor, naloxone or sulpiride. SB attenuated visceral allodynia and colonic hyperpermeability in animal IBS models. These actions may be AMPK and PPAR-γ dependent and also mediated by the NO, opioid and central dopamine D2pathways. Butyrate may be effective for the treatment of IBS.