黄芪汤上调肝组织BAMBI表达改善CCl4诱导小鼠肝纤维化
Huangqi decoction attenuates CCl4-induced liver fibrosis in mice through up-regulation of liver BAMBI expression
- 上海中医药杂志 2021年55卷第3期 页码：74-80
- 作者机构：
1.上海中医药大学附属曙光医院，肝病研究所，肝肾疾病病证教育部重点实验室，上海市重点实验室（上海 201203）
2.上海中医药大学交叉科学研究院（上海 201203）
3.上海中医药大学研究生院（上海 201203）
- 作者简介：
蒋微，女，硕士研究生，主要从事中医药防治慢性肝病的临床与基础研究工作
蒋式骊，主治医师；E-mail：shilijiang@hotmail.com
- 基金信息：国家自然科学基金项目(81603532)
DOI：10.16305/j.1007-1334.2021.2010021
中图分类号：
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蒋微, 徐莹, 王晓柠, 等. 黄芪汤上调肝组织BAMBI表达改善CCl4诱导小鼠肝纤维化[J]. 上海中医药杂志, 2021,55(3):74-80.
Wei JIANG, Ying XU, Xiaoning WANG, et al. Huangqi decoction attenuates CCl4-induced liver fibrosis in mice through up-regulation of liver BAMBI expression[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(3):74-80.
蒋微, 徐莹, 王晓柠, 等. 黄芪汤上调肝组织BAMBI表达改善CCl4诱导小鼠肝纤维化[J]. 上海中医药杂志, 2021,55(3):74-80. DOI： 10.16305/j.1007-1334.2021.2010021.
Wei JIANG, Ying XU, Xiaoning WANG, et al. Huangqi decoction attenuates CCl4-induced liver fibrosis in mice through up-regulation of liver BAMBI expression[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(3):74-80. DOI： 10.16305/j.1007-1334.2021.2010021.
摘要
目的,2,探讨黄芪汤（HQD）对肝纤维化模型小鼠骨形成蛋白和激活素跨膜抑制剂（BAMBI）的作用。,方法,2,以10% CCl,4,橄榄油溶液2 g/kg腹腔注射建立C57BL/6小鼠肝纤维化模型；于第4周起将造模组小鼠随机分为模型组（M）和黄芪汤组（HQD），每组12只，干预3周；检测各组小鼠的肝功能、肝组织BAMBI及相关胶原基因表达。体外培养LX-2细胞，观察HQD有效组分黄芪总皂苷（AS）和甘草酸（GA）对转化生长因子-β（TGF-β）信号传导和基因表达的影响。,结果,2,与模型组比较，HQD组血清丙氨酸氨基转移酶、门冬氨酸氨基转移酶活性显著降低（,P,<,0.01）；肝组织炎症坏死、胶原沉积均显著减轻（,P,<,0.01）；肝组织I型胶原（Col1a1）和基质金属蛋白酶-12 mRNA水平显著降低（,P,<,0.05），而,Bambi, mRNA表达显著增加（,P,<,0.01）。体外实验结果表明，AS和GA可显著抑制TGF-β1诱导的LX-2细胞活化和胶原合成；显著降低脂多糖诱导LX-2细胞的肿瘤坏死因子-α表达（,P,<,0.01），且显著增加LX-2细胞BAMBI表达（,P,<,0.01）。,结论,2,黄芪汤抗肝纤维化的作用机制可能与抑制肝脏炎症反应及上调BAMBI表达有关。
Abstract
Objective,2,To explore whether BMP and activin membrane bound inhibitor(BAMBI), an endogenous "pseudo-receptor" of transforming growth factor β(TGF-β), could be involved in the anti-liver fibrotic effects of Huangqi decoction(HQD).,Methods,2,Liver fibrosis was induced in male C57BL/6 mice by 10% CCl,4,(2 g/kg body weight,ip,), three times per week, for 6 weeks. From the 4th week, the CCl,4, model mice were randomly divided into two groups: treated with vehicle(M)and HQD, respectively, for 3 weeks through gavage. ,In vitro, cultured LX-2 cells(a human hepatic stellate cell line)were used to detect the effect of HQD’s major effective components astragalosides(AS)and glycyrrhizic acid(GA)on TGF-β signaling and gene expression.,Results,2,HQD treatment significantly attenuated CCl,4,-induced abnormal increase of serum ALT and AST(,P,<,0.01). H,&,E staining and Sirius red staining on liver tissue sections revealed that HQD treatment significantly attenuated CCl,4,-induced liver tissue damage and inflammation, and reduced liver collagen deposition. Real-time PCR results revealed that HQD treatment reduced the abnormal overexpression of collagen-1(,Col,1α1) and matrix metalloproteinase-12(,Mmp,-12)mRNA(,P,<,0.05). Furthermore, compared with the M group, the liver expression of ,Bambi, mRNA was significantly enhanced in the HQD group(,P,<,0.01). Cell culture studies demonstrated that the treatment of LX-2 cells with AS and GA inhibited TGF-β1-induced LX-2 cell activation and collagen synthesis, inhibited lipopolysaccharide-induced tumor necrosis factor-α expression(,P,<,0.01), and enhanced BAMBI expression(,P,<,0.01).,Conclusion,2,These results revealed that inhibiting liver inflammation and upregulating the expression of BAMBI could be one of the important mechanisms for HQD to effectively reduce liver fibrosis.
关键词
黄芪汤黄芪总皂苷甘草酸肝纤维化小鼠骨形成蛋白和激活素跨膜抑制剂TGF-β1
Keywords
Huangqi decoctiontotal astragalus saponinsglycyrrhizic acidliver fibrosisbone morphogenetic protein and activin transmembrane inhibitor (BAMBI)TGF-β1
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