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  

The effect of EGB on expression of TGFβ1, NF-κB, and FN in hepatic tissues from diabetic rats with non-alcoholic fatty liver disease

作　　者：王家员[1] 樊建霜[1] 吴亮[2] 黄卡特[2] 王蓉蓉[2] 

机构地区：[1]浙江中医药大学附属温州市中医院中药房,浙江温州325000 [2]温州医科大学附属第一医院病理科,浙江温州325015

出　　处：《温州医科大学学报》2016年第4期267-273,共7页Journal of Wenzhou Medical University

基　　金：温州市科技局科研基金资助项目(Y20120010)

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 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 m RNA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m RNA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m RNA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。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 m RNA 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 infl ammatory infi ltration and fi brosis. 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 m RNA 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 m RNA expression（P〈0.05） of diabetic rats livers decreased signifi cantly 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.

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 

分 类 号：R363[医药卫生—病理学]