选择性β3肾上腺素能受体激动剂对非酒精性脂肪性肝病大鼠血清氧化应激指标和肝组织纤维化的影响

doi:10.3969/j.issn.1672-5069.2018.03.017

摘要/Abstract

摘要： 目的探讨选择性β3肾上腺素能受体（β3-AR）激动剂对非酒精性脂肪性肝病（NAFLD）大鼠血清氧化应激反应和肝纤维化的影响。方法将30只SD大鼠随机分为对照组（NC组）、高脂模型（HC组）和β3-AR激动剂干预组（BRL组）,每组10只。采用ELISA法检测血清透明质酸（HA）和转化生长因子β1（TGF-β1）。使用分光光度计测定肝组织匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）水平。结果 BRL组血清TC、TG、ALT、AST、HA和TGF-β1水平分别为（1.95±0.43） mmol/L、（0.82±0.31） mmol/L、（71.02±11.34） U/L、（165.18±39.11） U/L、（159.64±32.50） ng/ml和（0.92±0.54） μg/ml,显著高于HC组【分别为（1.77±0.34） mmol/L、（0.59±0.23） mmol/L、（54.48±8.64） U/L、（134.12±37.16） U/L、（95.57±19.47） ng/ml和（0.75±0.51）μg/ml,P<0.05】,它们均显著高于对照组【分别为（1.19±0.25） mmol/L、（0.35±0.19） mmol/L、（32.26±7.13）U/L 、（119.64±35.16） U/L、（76.26±13.34） ng/ml 和（0.69±0.46） μg/ml,P<0.05];BRL组肝组织匀浆SOD和GSH-Px水平分别为（46.31±16.39）×103U/g protein和（98.64±19.33）mg/g protein,显著低于HC组的（79.26±15.34）×103U/g protein和（126.34±21.56） mg/g protein,而MDA水平为（8.16±0.92） μmol/L/g protein,显著高于HC组的（5.76±0.88）μmol/L/g protein（P<0.05）,而在NC组则分别为（113.34±12.26）×103U/g protein、（175.59±26.34）mg/g protein和（2.71±0.64）μmol/L/g protein ,与前两组比,差异显著（P<0.05）;BRL组肝组织脂肪变性、炎性浸润、气球样变和肝纤维化评分分别为（2.71±0.34）、（2.38±0.41）、（0.86±0.21）和（4.19±0.40,显著高于HC组【分别为（1.94±0.34）、（1.76±0.34）、（0.61±0.16）和（3.02±0.34）,P<0.05】。结论 β3-AR激动剂可加重NAFLD大鼠肝组织氧化应激损伤,促进肝纤维化进展。

关键词: 非酒精性脂肪性肝病, β, 3肾上腺素能受体激动剂, 氧化应激损伤, 肝纤维化

Abstract: Objective To investigate the effect of selective β3-adrenergic receptor（β3-AR） agonist on hepatic oxidative stress and liver fibrosis in rats with nonalcoholic fatty liver disease（NAFLD）. Methods 30 male SD rats were randomly divided into control （NC）,model and and β3-AR agonist （BRL 37344） intervention group （BRL） with ten in each. Serum hyaluronic acid （HA）and transforming growth factor-β1 （TGF-β1） were detected by ELISA. The superoxide dismutase （SOD）,malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） levels in liver tissue homogenates were detected by spectrophotometry. The liver tissues of rats were collected to examine the pathological changes and the degree of fibrosis. Results Serum TC,TG,ALT,AST,HA and TGF-β1 levels in BRL group were（1.95±0.43） mmol/L,（0.82±0.31） mmol/L,（71.02±11.34） U/L,（165.18±39.11） U/L, （159.64±32.50） ng/ml and（0.92±0.54） μg/ml,much higher than【（1.77±0.34） mmol/L,（0.59±0.23） mmol/L,（54.48±8.64）U/L,（134.12±37.16） U/L,（95.57±19.47） ng/ml and（0.75±0.51） μg/ml,respectively,P<0.05】 in model group,and they were all higher than 【（1.19±0.25） mmol/L,（0.35±0.19） mmol/L,（32.26±7.13）U/L,（119.64±35.16）U/L,（76.26±13.34）ng/ml and（0.69±0.46） μg/ml,respectively,P<0.05] in the NC group; hepatic SOD and GSH-Px levels in BRL were （46.31±16.39）×103U/g protein and（98.64±19.33） mg/g protein,much lower than （79.26±15.34）×103U/g protein and （126.34±21.56） mg/g protein,respectively in the model,while MDA level was（8.16±0.92）μmol/L/g protein,much higher than（5.76±0.88）μmol/L/g protein in the model （P<0.05）,and they were （113.34±12.26）×103U/g protein,（175.59±26.34）mg/g protein and（2.71±0.64） μmol/L/g protein in the control（P<0.05）;the scores of steatosis, inflammatory infiltration,ballooning degeneration and liver fibrosis in BRL were （2.71±0.34）,（2.38±0.41）,（0.86±0.21） and （4.19±0.40,much higher than【（1.94±0.34）,（1.76±0.34）,（0.61±0.16） and（3.02±0.34）,respectively,P<0.05】 in the model. Conclusion β3-AR agonist could aggravate hepatic oxidative stress and might improve liver fibrosis in rats with NAFLD,which warrants further investigation.

Key words: Nonalcoholic fatty liver disease, β3 adrenergic receptor agonist;, Oxidative stress, Liver fibrosis

王新伟, 吕柯, 孙晓, 张菊. 选择性β3肾上腺素能受体激动剂对非酒精性脂肪性肝病大鼠血清氧化应激指标和肝组织纤维化的影响[J]. 实用肝脏病杂志, 2018, 21(3): 384-387.

Wang Xinwei, Lyu Ke, Sun Xiao, et al. Effect of selective β3-adrenergic receptor agonist on hepatic oxidative stress and liver fibrosis in rats with nonalcoholic fatty liver disease[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 384-387.

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