Lovastatin inhibits visceral allodynia and increased colonic permeability induced by lipopolysaccharide or repeated water avoidance stress in rats.
Lovastatin inhibits visceral allodynia and increased colonic permeability induced by lipopolysaccharide or repeated water avoidance stress in rats.
复制标题
洛伐他汀可抑制大鼠脂多糖或反复回避水应激引起的内脏异常疼痛和结肠通透性增加。
DOI：
10.1016/j.ejphar.2017.10.056
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Okumura T
中科院分区：
文献类型：
--
作者：
Nozu T;Miyagishi S;Kumei S;Nozu R;Takakusaki K;Okumura T
据报道，他汀类药物可阻断炎性躯体疼痛，并具有抗细胞因子特性。脂多糖（LPS）或重复避水应激（WAS）诱导大鼠内脏高敏感性并增加肠道通透性，这是通过促炎性蛋白依赖性途径介导的。由于内脏高敏感性和肠道通透性增加在肠易激综合征（IBS）的病理生理学中起着至关重要的作用，因此认为上述动物模型可以模拟IBS。我们假设洛伐他汀通过减轻这些内脏变化来改善IBS患者的症状。用结肠球囊扩张法测定大鼠内脏感觉反应阈（VMR）。通过使用分光光度计定量结肠组织中吸收的伊文思蓝15分钟来体内测定结肠渗透性。皮下（皮下）注射LPS（1 mg/kg）3 h后，VMR阈值降低。用洛伐他汀（20 mg/kg s.c.每天一次，持续3天）通过LPS消除这种反应。重复WAS（1小时，每天3天）诱导内脏异常性疼痛，这也被重复注射洛伐他汀之前，每个应力会议。甲羟戊酸内酯、NG-硝基-L-精氨酸甲酯或纳洛酮可逆转洛伐他汀的镇痛作用。洛伐他汀还阻断LPS或重复WAS诱导的肠通透性增加。这些结果表明，洛伐他汀可能有助于治疗IBS。
Statins have been reported to block inflammatory somatic pain and have an anti-cytokine property. Lipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral hypersensitivity and increases gut permeability in rats, which are mediated through proinflammatory cytokine-dependent pathways. Since visceral hypersensitivity with increased gut permeability plays a crucial role in the pathophysiology of irritable bowel syndrome (IBS), these above animal models are considered to simulate IBS. We hypothesized that lovastatin improves symptoms in the patients with IBS by attenuating these visceral changes. The threshold of visceromotor response (VMR) induced by colonic balloon distention was measured for the assessment of visceral sensation in rats. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue in colonic tissue for 15 min using a spectrophotometer. Subcutaneously (s.c.) injected LPS (1 mg/kg) reduced the threshold of VMR after 3 h. Pretreatment with lovastatin (20 mg/kg s.c. daily for 3 days) abolished this response by LPS. Repeated WAS (1 h daily for 3 days) induced visceral allodynia, which was also blocked by repeated injection of lovastatin before each stress session. The antinociceptive effect of lovastatin on the LPS-induced allodynia was reversed by mevalonolactone, NG-nitro-L-arginine methyl ester or naloxone. Lovastatin also blocked the LPS- or repeated WAS-induced increased gut permeability. These results indicate the possibility that lovastatin can be useful for treating IBS.