Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model

被引：27

作者：

Nozaki, Yuichi ^{[1
,2
]}

Fujita, Koji ^{[1
]}

Wada, Koichiro ^{[3
]}

Yoneda, Masato ^{[1
]}

Kessoku, Takaomi ^{[1
]}

Shinohara, Yoshiyasu ^{[1
]}

Imajo, Kento ^{[1
]}

Ogawa, Yuji ^{[1
]}

Nakamuta, Makoto ^{[4
]}

Saito, Satoru ^{[1
]}

Masaki, Naohiko ^{[5
]}

Nagashima, Yoji ^{[6
]}

Terauchi, Yasuo ^{[7
]}

Nakajima, Atsushi ^{[1
]}

机构：

[1] Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Natl Ctr Global Hlth & Med, Dept Gastroenterol, Shinjuku Ku, Tokyo 1628655, Japan

[3] Osaka Univ, Grad Sch Dent, Dept Pharmacol, Suita, Osaka 5650871, Japan

[4] Natl Hosp Org, Kyushu Med Ctr, Dept Gastroenterol, Chou Ku, Fukuoka 8108563, Japan

[5] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Ichikawa 2728516, Japan

[6] Yokohama City Univ, Grad Sch Med, Dept Mol Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[7] Yokohama City Univ, Grad Sch Med, Dept Endocrinol & Metab, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

来源：

BMC GASTROENTEROLOGY | 2015年 / 15卷

基金：

日本科学技术振兴机构;

关键词：

NOS; NASH; Inflammation; Fibrosis; NF-kB; NITRIC-OXIDE SYNTHASE; TRIGLYCERIDE TRANSFER PROTEIN; INSULIN-RESISTANCE; DAMAGE; INHIBITION; STEATOSIS; ENDOTOXIN;

D O I：

10.1186/s12876-015-0269-3

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Background: Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions. Methods: iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed. Results: Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions. Conclusions: iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.

引用

页数：14

共 36 条

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Deletion of Inducible Nitric-Oxide Synthase in Leptin-Deficient Mice Improves Brown Adipose Tissue Function [J].