棉酚对糖尿病大鼠非酒精性脂肪性肝病纤维化的影响

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摘要目的：研究棉酚对糖尿病大鼠非酒精性脂肪性肝病（NAFLD）纤维化的影响及其可能机制。方法：雄性SD大鼠30只，随机均分成3组：正常对照（NC）组、2型糖尿病（T2DM）组、棉酚治疗（T2DMG）组。采用高脂饮食及低剂量链脲佐菌素（STZ）构建糖尿病大鼠模型，T2DMG组模型构建后用棉酚灌胃（15 mg·kg-1·d-1灌胃4周，再按每周15 mg·kg-1灌胃8周）。光镜及电镜下观察肝组织形态学改变；Masson染色观察肝组织纤维化病变；免疫组织化学检测肝组织α-平滑肌肌动蛋白（α-SMA）、11β-羟类固醇脱氢酶1（11β-HSD1）、糖皮质激素受体（GR）、核转录因子-κB（NF-κB）及转化生长因子β1（TGFβ1）蛋白的表达；RT-PCR法检测肝组织11β-HSD1、GR、NF-κB及TGFβ1 mRNA表达。结果：与NC组比较，T2DM组肝组织明显纤维化，α-SMA、11β-HSD1、GR、NF-κB、TGFβ1蛋白表达明显增多（P=0.001、0.004、0.001、0.001、0.002），GR、TGFβ1 mRNA表达明显增加（P=0.01、0.001）；与T2DM组比较，T2DMG组肝纤维化病变明显减轻，肝组织α-SMA、11β-HSD1、GR、NF-κB、TGFβ1蛋白表达明显减少（P=0.009、0.031、0.002、0.009、0.027），11β-HSD1、GR、TGFβ1 mRNA表达明显减少（P=0.003、0.038、0.014）。结论：棉酚可以有效改善NAFLD相关肝纤维化病变，其机制可能是抑制肝脏11β-HSD1、GR、NF-κB、TGFβ1的表达。

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	李秧秧
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	万丽
	陈国荣
	陈垒
	陈三妹
	王蓉蓉

关键词 ：肝纤维化, 糖尿病, 棉酚, 11&beta, -羟类固醇脱氢酶1, 糖皮质激素受体, 核转录因子-&kappa, B, 转化生长因子&beta, 1

Abstract：Objective: To investigate the effect of gossypol on nonalcoholic fatty liver disease (NAFLD) and its mechanism. Methods: Thirty male Sprague-Dawley rats were divided randomly into 3 groups: normal control (NC) group, type 2 diabetes mellitus (T2DM) group, type 2 diabetes mellitus treated with gossypol (T2DMG) group. After fed with a high-fat diet, the rats were injected with low-dose streptozotocin (STZ) intraperitoneally to induce type 2 diabetes mellitus. The T2DMG group were given 15 mg•kg-1•d-1 gossypol by gavage for 4 weeks, followed by 15 mg•kg-1•d-1 dose of gossypol every week for 8 weeks. The morphology of the liver was observed under light and transmission electronmicroscopy. Masson staining were used to observe the fibrosis of liver tissue. The protein expression of α-SMA, 11β-HSD1, GR, NF-κB and TGFβ1 were assayed by immunohistochemistry. The mRNA expression of 11β-HSD1, GR, NF-κB and TGFβ1 from rats livers were assayed by semi-quantitative RT-PCR. Results: Compare with NC group, T2DM group hapatic fibrosis was obvious, α-SMA, 11β-HSD1, GR, NF-κB and TGFβ1 protein expression was significantly enhanced (P=0.001, 0.004, 0.001, 0.001, 0.002), GR and TGFβ1 mRNA expression was significantly increased (P=0.01, 0.001). Compare with T2DM group, T2DMG group liver fibrosis was significantly ameliorated, α-SMA, 11β-HSD1, GR, NF-κB and TGFβ1 expression was significantly decreased (P=0.009, 0.031, 0.002, 0.009, 0.027), 11β-HSD1, GR and TGFβ1 mRNA expression was significantly reduced (P=0.003, 0.038, 0.014). Conclusion: Gossypol exerts the capacity to relieve hepatic fibrosis from NAFLD, inhibiting the expression of 11β-HSD1, GR and NF-κB, TGFβ1 may be involved in it.

Key words： liver fibrosis diabetes mellitus gossypol 11β-hydroxysteroid dehydrogenase 1 glucocorticoid receptor nuclear transcription factor-κB transforming growth factor-β1

收稿日期: 2017-04-24

基金资助:浙江省公益性技术应用研究计划项目（Y2011c23123）；温州市科技局科研基金资助项目（Y20120010，Y20130166）。

通讯作者: 王蓉蓉，副主任医师，Email：997683344@qq.com

作者简介: 李秧秧（1986-），女，浙江温州人，住院医师。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I11/786

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