基于NF-κB/IL-1β通路探讨金银花总皂苷对铅中毒大鼠的保肝作用

摘要/Abstract

摘要： 目的基于核转录因子-κB （nuclear factor kappa-B,NF-κB）/白介素-1β（interleukin-1β,IL-1β）通路探讨金银花总皂苷对铅中毒大鼠的保肝作用。方法清洁级SD大鼠100只分为正常对照组、模型对照组、金银花总皂苷低、中、高剂量组,除正常对照组外,其余各组大鼠每日腹腔注射醋酸铅溶液（10 mg/kg）,持续4周;期间,金银花总皂苷低、中、高剂量组大鼠每日予以相应剂量的金银花总皂苷灌胃,正常对照组、模型对照组给予等体积的生理盐水灌胃。试验结束后获取大鼠血清及肝脏,测定肝/体比值、肝铅含量、血清丙氨酸转氨酶（alanine aminotransferase,ALT）、天冬氨酸转氨酶（aspartate aminotransferase,AST）、γ-谷氨酰转移酶（gamma-glutamyltransferase,GGT）水平、肝丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（superoxide dismutase,SOD）和谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）水平,反转录-聚合酶链反应（reverse transcription-polymerase chain reaction,RT-PCR）法及蛋白印迹法测定肝NF-κB和IL-1β水平。结果与正常对照组比较,模型对照组体质量、SOD、GSH-Px水平降低,肝/体比值、肝铅含量、血清AST[（256.32±16.24）vs（46.81±15.24）μ/L]、ALT[（354.32±18.54）vs（35.36±15.85）μ/L]、GGT水平[（5.64±0.31）vs（0.94±0.24）μ/L]、肝MDA水平[（654.49±16.29）vs（266.54±15.52）ng/g]、肝NF-κB、IL-1β mRNA蛋白表达水平[0.82±0.28 vs 3.61±0.23,0.48±0.29 vs 3.71±0.32,0.49±0.12 vs 1.69±0.11, 0.38±0.16 vs 1.98±0.14]升高（P<0.05）;与模型对照组比较,金银花总皂苷低、中、高剂量组体质量、SOD、GSH-Px水平降低升高,肝/体比值、肝铅含量、血清AST[（88.32±15.74）vs（135.20±10.8）、（186.28±12.27）、（256.32±16.24）μ/L]、ALT[（154.68±19.78）vs（204.28±20.47）、（257.68±19.44）、（354.32±18.54）μ/L]、GGT水平[（2.23±0.27）vs（3.27±0.34）、（4.73±0.27）、（5.64±0.31）μ/L]、肝MDA水平[（358.58±15.41）vs（485.52±10.59）、（588.69±12.53）、（654.49±16.29）ng/g]、肝NF-κB、IL-1β mRNA蛋白表达水平降低（3.61±0.23 vs 2.89±0.25、2.29±0.21、1.65±0.27,3.71±0.32 vs 2.93±0.30、2.33±0.29、1.15±0.24,1.69±0.11 vs 1.39±0.10、0.95±0.14、0.74±0.13,1.98±0.14 vs 1.35±0.15、0.89±0.14、0.53±0.13）（P<0.05）;且随着金银花总皂苷剂量的增加,金银花总皂苷低、中、高剂量组体质量、SOD、GSH-Px水平逐渐升高,肝/体比值、肝铅含量、血清AST、ALT、GGT水平、肝MDA水平、肝NF-κB、IL-1β mRNA蛋白表达水平逐渐降低,具有明显剂量-效应关系（P<0.05）。结论金银花总皂苷能明显减轻铅中毒大鼠肝氧化损伤及炎症反应,具有明显肝保护作用,其机制可能与金银花总皂苷抑制铅中毒大鼠肝NF-κB/IL-1β通路的激活有关。

关键词: NF-κB, IL-1β, 金银花总皂苷, 铅, 保肝

Abstract: Objective To investigate the hepatoprotective effect of total saponins of honeysuckle on lead poisoning rats based on nuclear factor kappa-B（NF-κB）/interleukin-1β（IL-1β） pathway. Methods 100 clean SD rats were divided into normal control group,model control group,low,medium and high dose groups of total honeysuckle saponins. Except the normal control group,the other groups were injected with lead acetate solution（10 mg/kg） for four weeks. During this period,the rats in the low,medium and high dose groups of total honeysuckle saponins were given the corresponding doses of total honeysuckle saponins by gavage every day,and the normal control group and the model control group were given the same volume of normal saline by gavage. After the test,the rat serum and liver were obtained,and the liver/body ratio,liver lead content,serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,gamma-glutamyltransferase（GGT）,malondialdehyde（MDA）,superoxide dismutase（SOD） and glutathione peroxidase（GSH-Px） levels were determined. The reverse transcription-polymerase chain reaction（RT-PCR） and Western blotting were used to determine liver NF-κB and IL-1β levels. Results Compared with the normal control group,the body weight,SOD and GSH-Px levels of the model control group decreased,liver/body ratio,liver lead content,serum AST[（256.32±16.24）vs（46.81±15.24）μ/L],ALT[（354.32±18.54）vs（35.36±15.85）μ/L],GGT level[（5.64±0.31）vs（0.94±0.24）μ/L],liver MDA level[（654.49±16.29）vs（266.54±15.52）ng/g],liver NF-κB and IL-1β mRNA protein expression levels[0.82±0.28 vs 3.61±0.23, 0.48±0.29 vs 3.71±0.32,0.49±0.12 vs 1.69±0.11,0.38±0.16 vs 1.98±0.14]increased（P<0.05）. Compared with the model control group,the body weight,SOD,GSH-Px levels in the low,medium and high dose groups of total saponins of honeysuckle decreased,serum AST[（88.32±15.74）vs（135.20±10.8）,（186.28±12.27）,（256.32±16.24）μ/L],ALT[（154.68±19.78）vs（204.28±20.47）,（257.68±19.44）,（354.32±18.54）μ/L],GGT level[（2.23±0.27）vs（3.27±0.34）,（4.73±0.27）,（5.64±0.31）μ/L],liver MDA level[（358.58±15.41）vs（485.52±10.59）,（588.69±12.53）,（654.49±16.29）ng/g],liver NF-κB and IL-1β mRNA protein expression levels decreased（3.61±0.23 vs 2.89±0.25,2.29±0.21,1.65±0.27,3.71±0.32 vs 2.93±0.30,2.33±0.29. 1.15±0.24,1.69±0.11 vs 1.39±0.10,0.95±0.14,0.74±0.13,1.98±0.14 vs 1.35±0.15,0.89±0.14,0.53±0.13）（P<0.05）. With the increase of total honeysuckle saponin dose,the body weight,SOD and GSH-Px levels of the low,medium and high dose groups of total honeysuckle saponins gradually increased,and the liver/body ratio,liver lead content,serum AST,ALT,GGT levels,liver MDA level,liver NF-κB,IL-1β mRNA protein expression levels gradually decreased,with a significant dose-effect relationship（P<0.05）. Conclusion The total honeysuckle saponins can significantly reduce liver oxidative damage and inflammatory response in lead poisoning rats,and have obvious hepatoprotective effects,its mechanism may be related to the inhibition of liver NF-κB/IL-1β pathway activation by total honeysuckle saponins in lead poisoning rats.

Key words: NF-κB, IL-1β, Total honeysuckle saponins, Lead, Liver protection

中图分类号:

R-332

黄华, 郑冲, 张凯. 基于NF-κB/IL-1β通路探讨金银花总皂苷对铅中毒大鼠的保肝作用. [J]职业与健康, 2023, 39(5): 620-625.

HUANG Hua, ZHENG Chong, ZHANG Kai. Study on hepatoprotective effect of total honeysuckle saponins on lead poisoning rats based on NF-κB/IL-1β pathway. [J]OCCUPATION AND HEALTH, 2023, 39(5): 620-625.

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