科研之友
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摘要
Nonalcoholic fatty liver disease (NAFLD) is classically associated with insulin resistance and the inflammatory response, especially in the nonalcoholic steatohepatitis phase. The liver X receptors (LXRs) play a critical role in the regulation of cholesterol metabolism and inflammatory processes. @@@ Wild-type C57BL/6 mice were fed a normal diet (ND) or a high-fat (HF) diet for 8 weeks. Some ND- and HF-fed mice were treated (i.p.) with the LXR agonist T0901317 (30 mg/kg/day) for 7 days. Lipopolysaccharide (LPS, 50 mu g/mouse) was then injected intraperitoneally to induce liver injury. The activation of MAPKs, NF-kappa B and the PI3K pathway was evaluated using Western blot. Bone marrow-derived macrophages (MDMs) were isolated from the femurs of C57BL/6 mice and cultured with or without T0901317 (20 mu mol/l). The expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) was evaluated in vitro or in vivo using real-time PCR, immunohistochemistry, or Western blot. @@@ The LXR agonist T0901317 attenuated LPS-induced liver injury in a murine model of NAFLD, reflected by reduced serum alanine aminotransferase and aspartate aminotransferase levels, and reduced liver histology changes. Activation of LXRs reduced TNF-alpha and iNOS expression through inhibiting JNK and the PI3K signaling pathway. An in vitro study demonstrated that the activation of LXR inhibited the expression of TNF-alpha and iNOS in the MDMs of mice. @@@ Activation of LXRs attenuates LPS-induced liver injury in murine NAFLD through inhibiting the pro-inflammatory activity of macrophages.
- 出版日期2012-2
- 单位上海交通大学
