银杏叶提取物对非酒精性脂肪性肝病肝组织TGFβ1、NF-κB、FN表达的影响

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摘要目的：观察银杏叶提取物（EGB）对糖尿病大鼠非酒精性脂肪性肝病（NAFLD）的影响，并探讨其作用机制。方法：雄性SD大鼠30只随机均分成正常对照组、2型糖尿病组和EGB治疗组。采用高脂饮食加小剂量（30 mg/kg）链脲佐菌素（STZ）诱导2型糖尿病大鼠模型，EGB治疗组给予50 mg·kg-1·d-1的EGB连续灌胃12周。HE染色光镜下观察肝组织的形态学改变；VG染色光镜下观察肝脏组织的纤维化病变；免疫组织化学法检测肝组织核转录因子Kappa B（NF-κB P65）、转化生长因子β1（TGFβ1）、纤维连接蛋白（FN）以及α-平滑肌肌动蛋白（α-SMA）表达；RT-PCR法检测肝组织NF-κB、TGFβ1、FN mRNA表达。结果：糖尿病大鼠肝细胞出现脂肪变性、气球样变、炎症以及肝纤维化等NAFLD的病理变化；免疫组织化学染色结果显示糖尿病大鼠肝组织出现较多的α-SMA阳性表达的活化的肝星形细胞（HSC），NF-κB P65、TGFβ1、FN蛋白表达显著高于正常对照组（P＜0.05，P＜0.01，P＜0.05），部分肝细胞NF-κB P65呈核阳性表达；RT-PCR显示糖尿病大鼠肝组织TGFβ1、FN基因mRNA表达显著高于正常对照组（P＜0.01，P＜0.05）。经EGB治疗后，肝细胞脂肪变性、气球样变及炎症现象得到明显改善，纤维化程度明显减轻；肝组织α-SMA阳性表达的活化的HSC数量明显减少（P＜0.05）；NF-κB P65、TGFβ1、FN蛋白表达明显下降（均P＜0.05）；TGFβ1、FN基因mRNA表达也明显下降（均P＜0.05）。结论：EGB可明显减轻糖尿病大鼠NAFLD的程度，其机制可能与抑制肝脏NF-κB、TGFβ1、FN的表达有关。

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关键词 ：糖尿病, 2型；非酒精性脂肪性肝病；银杏叶提取物；大鼠

Abstract：Objective: To observe the effect of extract of ginkgo biloba (EGB) on hepatic tissue from DM rats with non-alcoholic fatty liver disease (NAFLD). Methods: Thirty male Sprague-Dauley rats were divided randomly into three groups: normal control group, type 2 diabetic group and EGB-treated group. After being fed with high-fat feeding for 4 weeks, the later groups were injected with low dosage strepozotocin (30 mg/kg) intraperitoneally to induce NAFLD model of type 2 diabetes mellitus. The EGB treated group was gavaged with EGB at the dosage of 50 mg·kg-1·d-1 for 12 weeks. The pathologic changes of liver was observed under light microscopy (LM) stained with HE and VG staining respectively. Additionally, the protein expression of NF-κB, TGFβ1, FN, α-SMA were assayed by immunohistochemistry (IHC), the mRNA expression of TGFβ1, NF-κB, FN from rats livers were assayed by semi-quantitative RT-PCR. Results: Liver specimen from diabetic rats stained by HE and VG showed obvious liver fatty degeneration, ballooning degeneration, dotty necrosis necrosis with accompanying inflammatory infiltration and fibrosis. Meanwhile, we discovered that there were a great number of α-SMA reactive hepatic stellate cells in diabetic rats liver tissue. In addition, the protein expression of NF-κB, TGFβ1, FN (P<0.05, P<0.01, P<0.05) and the TGFβ1, FN mRNA expression (P<0.01, P<0.05) of diabetic rats livers were significantly higher than that of the normal control group. After treatment with EGB, the pathological change of liver and proliferation of hepatic stellate cell in diatetic rats relieved (P<0.05).Meanwhile, the protein expression of NF-κB, TGFβ1, FN (P<0.05) and the TGFβ1, FN mRNA expression (P<0.05) of diabetic rats livers decreased significantly compared with type 2 diabetic group. Conclusion: EGB can relieve NAFLD from diabetic rats. Down regulation of expression of NF-κB, TGFβ1, FN may be involved in it

Key words： diabetes mellitus, type 2 non-alcoholic fatty liver disease extract of ginkgo biloba rats

收稿日期: 2015-09-16

基金资助:温州市科技局科研基金资助项目（Y20120010）。

通讯作者: 王蓉蓉，副主任医师，Email：hulangwang307@163.com。

作者简介: 王家员（1976-），男，浙江温州人，主管药师。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2016/V46/I4/267

[1] FARRELL G C, CHITTURI S, LAU G K, et al. Guidelinez for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary [J]. Gastroenterol Hepatol, 2007, 22(6): 775-777.
[2] TARGHER G, VALBUSA F, BONAPACE S, et al. Association of nonalcoholic fatty liver disease with QTc interval in patients with type 2 diabetes[J]. Nutr Metab Cardiovasc Dis, 2014, 24(6): 663-669.
[3] DIXON J B. Surgical management of obesity in patients with morbid obesity and nonalcoholic fatty liver disease[J]. Clin Liver Dis, 2014, 18(1): 129-146.
[4] GERTZ H J, KIEFER M. Review about Ginkgo bilkgo special extract EGb 761(Ginkgo)[J]. Curr Pharm Des, 2004, 10(3): 261-264.
[5] 郭啸华, 刘志红, 李恒, 等. 实验性2型糖尿病大鼠模型的建立[J]. 肾脏病与透析肾移植杂志, 2000, 9(4): 351-356.
[6] TOBLLI J E, FERDER L, STELLA I, et al. Enalapril prevents fatty liver in nephrotic rats[J]. J Nephrol, 2002, 15(4): 358-367.
[7] LO L, MCLENNAN S V, WILLIAMS P F, et al. Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse obesity model of non-alcoholic steatohepatitis[J]. J Hepatol, 2011, 55(2): 435-444.
[8] QU F, GAO H, ZHU S, et al. TRAF6-dependent Act 1 phosphorylation by the IκB Kinase–related kinases suppresses interleukin17-induced NF-κB activatin[J]. Mol Cell Biol,2012, 32(19): 3925-3937.
[9] QIU M, CHEN Y, CHU Y, et al. Zinc ionophores pyrithione inhibits herpes simplex virus replication through interfering with proteasome function and NF-κB activation[J] .Antiviral Res, 2013, 100(1): 44-53.
[10] BENARD C, CULTRONE A, MICHEL C, et al. Degraded carrageenan causing colitis in rats induces TNF Secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation[J]. PloS One, 2010, 5(1): e8666.
[11] CARDOZO A K, HEIMBEIG H, HEREMANS Y, et al. A comprehensive analysis of cytokine induced and nucler factor-kappa B-dependent genes in primary rat pancreatic beta-cells[J]. J Biol Chem, 2001, 276(52): 48879-48886.
[12] TANIGUCHI H, KATO N, OT SUKA M, et al. Hepatitis C virus core protein upregulates transforming growth factor-beta1 transcription[J]. J Med Virol, 2004, 72(1): 52-59.
[13] CHEN C S, WU C H, LAI Y C, et al. NF-kappaB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis[J]. Toxicology, 2008, 246(2-3): 148-157.
[14] WIERZBICKA-PATYNOWSKI I, SCHWARZBAUER J E. The ins and outs of fibronectin matrix assembly[J]. J Cell Sci, 2003, 116(Pt 16): 3269-3276.