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罗格列酮对非酒精性脂肪性肝病大鼠模型肝脏白细胞介素-18生成的抑制作用

Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease.

作者信息

Wang Hai-Ning, Wang Yan-Rong, Liu Guo-Qiang, Liu Zhe, Wu Pei-Xian, Wei Xiao-Ling, Hong Tian-Pei

机构信息

Department of Endocrinology, Peking University, Third Hospital, Beijing 100191, China.

出版信息

World J Gastroenterol. 2008 Dec 21;14(47):7240-6. doi: 10.3748/wjg.14.7240.

Abstract

AIM

To investigate the effects of rosiglitazone (RGZ) on expression of interleukin-18 (IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease (NAFLD) rats.

METHODS

Twenty-eight Sprague-Dawley (SD) rats were randomly divided into control, NAFLD, and RGZ treated NAFLD groups. A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk. The NAFLD animals were treated with RGZ or vehicle for the last 4 wk (week 9-12) and then sacrificed to obtain liver tissues. Histological changes were analyzed with HE, oil red O and Masson's trichrome staining. Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis.

RESULTS

The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group. Steatosis, inflammation and fibrosis, found in the liver of NAFLD rats, were significantly improved 4 wk after RGZ treatment. The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.

CONCLUSION

RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats. The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.

摘要

目的

探讨罗格列酮(RGZ)对非酒精性脂肪性肝病(NAFLD)大鼠肝脏中白细胞介素-18(IL-18)和半胱天冬酶-1表达的影响。

方法

将28只Sprague-Dawley(SD)大鼠随机分为对照组、NAFLD组和RGZ治疗的NAFLD组。通过给动物喂食高脂饮食12周建立NAFLD大鼠模型。在最后4周(第9 - 12周)对NAFLD动物用RGZ或赋形剂进行处理,然后处死以获取肝脏组织。用苏木精-伊红(HE)、油红O和Masson三色染色分析组织学变化。采用免疫组织化学染色和半定量逆转录聚合酶链反应(RT-PCR)分析检测IL-18和半胱天冬酶-1的表达。

结果

NAFLD组肝脏中IL-18和半胱天冬酶-1的表达水平均高于对照组。在NAFLD大鼠肝脏中发现的脂肪变性、炎症和纤维化在RGZ治疗4周后明显改善。RGZ治疗后,NAFLD组肝脏中升高的IL-18和半胱天冬酶-1表达也显著减弱。

结论

RGZ治疗可改善NAFLD大鼠肝脏中IL-18产生增加和组织学变化。RGZ对NAFLD的有益作用可能部分归因于其对肝脏IL-18产生的抑制作用。

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