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黄芪总黄酮对硫代乙酰胺诱导大鼠肝纤维化及NF-κB信号通路的影响

Effect of total flavonoids of astragalus on thioacetamide-induced liver fibrosis and NF-κB signaling pathway in rats
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摘要 目的探讨黄芪总黄酮(total flavonoids of astragalus,TFA)对硫代乙酰胺诱导大鼠肝纤维化及核因子-κB(nuclear factor-κB,NF-κB)信号通路的影响及其保护肝纤维化的可能作用机制。方法根据随机数字法将78只大鼠分为正常组、模型组、TFA低剂量组、TFA中剂量组、TFA高剂量组、阳性药物组,每组13只。全自动生化分析仪测定血清门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、谷丙氨酸氨基转移酶(alanine aminotransferase,ALT)水平。酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定羟脯氨酸(hydroxyproline,Hyp)、Ⅲ型前胶原氨基端肽(procollagen type III aminoterminal propeptide,PⅢNP)、Ⅰ型胶原(collagen type I,Col-Ⅰ)、IV型胶原(collagen type IV,Col-Ⅳ)水平。伊红-苏木素(hematoxylin-eosin,HE)染色和Masson染色测定肝组织病理学变化。Western blot测定各组大鼠肝组织肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)、基质金属蛋白酶(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制因子(tissue inhibitor of metalloproteinase,TIMP)蛋白水平。S-P免疫组化测定肝组织NF-κB P50、NF-κB P65蛋白表达。结果与模型组相比,TFA各剂量组大鼠体重增长量明显增加,肝指数明显降低,差异均有统计学意义[(131.50±27.90)g比(142.44±23.32)g比(155.65±22.88)g比(156.06±15.83)g,(6.28±0.53)%比(5.59±0.72)%比(5.55±0.52)%比(5.13±0.77)%,F值分别为23.66和46.41,P值均<0.05]。与模型组比较,TFA各剂量组大鼠血清AST、ALT水平明显降低,血清Hyp、PIIINP、Col-I、Col-IV含量明显降低,差异均有统计学意义[AST(U/L):(270.35±28.63)比(217.58±20.52)比(188.27±40.50)比(183.65±27.38),ALT:(432.30±39.24)比(294.36±47.49)比(290.30±49.41)比(267.78±45.34),Hyp(μg/L):(12.51±0.46)比(5.67±0.97)比(5.39±0.56)比(4.67±0.74),PIIINP(μg/L):(23.79±2.94)比(21.58±2.83)比(18.84±1.68)比(16.50±2.04),C Objective To explore the effect of total flavonoids of astragalus(TFA)on thioacetamide-induced liver fibrosis and nuclear factor-κB(NF-κB)signaling pathway and its possible mechanism of protecting liver fibrosis.Methods Total of 78 rats were randomly divided into normal group,model group,TFA low-dose group,TFA middle-dose group,TFA high-dose group and positive drug group accorded to the random number method,with 13 rats in each group.The aspartate aminotransferase(AST),alanine aminotransferase(ALT)levels were measured by an automatic biochemical analyser.Hydroxyproline(Hyp),procollagen type III aminoterminal propeptide(PIIINP),collagen type I(Col-I)and collagen type IV(Col-IV)levels were measured by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining and Masson staining were used to detect the pathological changes of liver tissue.Western blot were used to test the tumor necrosis factor-α(TNF-α),intercellular adhesion molecule-1(ICAM-1),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase(TIMP)protein levels in rats.S-P immunohistochemistry was used to determine the protein expression of NF-κB P50 and NF-κB P65 in liver tissue.Results Compared with the model group,mice in groups treated with various doses of TFA possessed an obviously increased weight and an apparent decreased liver index[(131.50±27.90)g vs(142.44±23.32)g vs(155.65±22.88)g vs(156.06±15.83)g,(6.28±0.53)%vs(5.59±0.72)%vs(5.55±0.52)%vs(5.13±0.77)%,F values were 23.66 and 46.41 respectively,both P values<0.05].Compared with the model group,serum AST、ALT levels and serum Hyp,PIIINP,Col-I and Col-IV contents were significantly decreased in groups treated with various doses of TFA[AST(U/L):(270.35±28.63)vs(217.58±20.52)vs(188.27±40.50)vs(183.65±27.38),ALT:(432.30±39.24)vs(294.36±47.49)vs(290.30±49.41)vs(267.78±45.34),Hyp(μg/L):(12.51±0.46)vs(5.67±0.97)vs(5.39±0.56)vs(4.67±0.74),PIIINP(μg/L):(23.79±2.94)vs(21.58±2.83)vs(18.84±1.68)vs(16.50±2.04),Col-I(μg/L):(825.32±43.97)vs(771.3
作者 黄睿 王倩 贾海英 Huang Rui;Wang Qian;Jia Haiying(Clinical Laboratory Center,People’s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)
出处 《国际免疫学杂志》 CAS 2022年第5期456-463,共8页 International Journal of Immunology
基金 新疆维吾尔自治区自然科学基金(2109D01C103)。
关键词 黄芪总黄酮 肝纤维化 炎症 核因子-ΚB Total flavonoids of astragalus Liver fibrosis Inflammation Nuclear factor-κB
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