Lovastatin inhibits visceral allodynia and increased colonic permeability induced by lipopolysaccharide or repeated water avoidance stress in rats.
著者
野津, 司
(Nozu, Tsukasa)
宮岸, 沙織
(Miyagishi, Saori)
粂井, 志麻
(Kumei, Shima)
野津, 麟太郎
(Nozu, Rintaro)
高草木, 薫
(Takakusaki, Kaoru)
奥村, 利勝
(Okumura, Toshikatsu)
上位タイトル
European Journal of Pharmacology
Vol.818,
(2018.
1)
,p.228-
234
識別番号
ISSN
0014-2999
DOI
10.1016/j.ejphar.2017.10.056
その他
PMID：29107672
抄録
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 15min using a spectrophotometer. Subcutaneously (s.c.) injected LPS (1mg/kg) reduced the threshold of VMR after 3h. Pretreatment with lovastatin (20mg/kg s.c. daily for 3 days) abolished this response by LPS. Repeated WAS (1h 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.
