3-巯基丙酮酸转硫酶在非酒精性脂肪性肝病中对脂肪变性的影响研究Effect of 3-mercaptopyruvate sulfur transferase on steatosis in non-alcoholic fatty liver disease
阙扬铭;朱华丽;周雪峰;李兵兵;吴佳燕;刘海燕;
摘要(Abstract):
目的探讨3-巯基丙酮酸转硫酶(MPST)在非酒精性脂肪性肝病(NAFLD)中对脂肪变性的影响。方法取20只C57BL/6小鼠,高脂饮食喂养,建立NAFLD模型,分为观察组和对照组(每组10只)。另以10只小鼠予以正常饮食用来参照NAFLD模型的成功建立。观察组小鼠注射重组腺病毒载体shRNA(AD-shRNA)对肝脏MPST进行干预,对照组小鼠注射重组腺病毒载体(AD-GFP)。小鼠处死后取肝组织进行HE染色,观察肝脏脂肪变性情况,并测定肝组织MPST、固醇调节元件结合蛋白-1(SREBP-1)、脂肪酸合成酶(FAS)、胱硫醚γ裂解酶(CSE)表达与肝脏中游离脂肪酸(FFA)、三酰甘油(TG)、总胆固醇(TC)、硫化氢(H_2S)的含量。结果观察组小鼠肝脏MPST的mRNA表达水平与对照组相比显著下调,FFA、TG、TC含量与对照组相比也显著降低,差异有统计学意义(P<0.05)。对照组小鼠肝脏内弥漫性肝细胞脂肪变性,且出现肝细胞炎性表现;观察组小鼠肝细胞脂肪变性的弥漫性减轻,炎性肝细胞减少。观察组小鼠肝脏SREBP-1、FAS的mRNA表达水平与对照组相比显著下调,CSE的mRNA表达水平及肝组织H_2S含量较对照组显著升高,差异有统计学意义(P<0.05)。结论 H_2S在MPST对脂肪肝的调节过程中起主要介导作用,且与SREBP-1相关通路抑制有关。
关键词(KeyWords): 非酒精性脂肪性肝病;3-巯基丙酮酸转硫酶;脂肪变性;游离脂肪酸;固醇调节元件结合蛋白-1
基金项目(Foundation): 浙江省科技计划项目(2014C33208)
作者(Authors): 阙扬铭;朱华丽;周雪峰;李兵兵;吴佳燕;刘海燕;
DOI: 10.14053/j.cnki.ppcr.202006011
参考文献(References):
- [1] 刘国旺,唐克诚.老年非酒精性脂肪肝研究进展[J].中国老年学杂志,2018,38(20):5117-5119.
- [2] 王梦瑶,黄志军.非酒精性脂肪肝治疗新药研究进展[J].中国临床药理学杂志,2018,34(20):2452-2455.
- [3] 郑乃汭.硫化氢对肥胖小鼠肝脂质蓄积的影响[J].中国药理学通报,2015,31(7):945-951.
- [4] 李檬,虞朝辉,厉有名,等.脂肪肝靶点新启示:关注3-巯基丙酮酸转硫酶/硫化氢通路[J].中华内科杂志,2019,58(3):220.
- [5] Spangler LC,Cline JP,Kiely CJ,et al.Low temperature aqueous synthesis of size-controlled nanocrystals through size focusing:a quantum dot biomineralization case study[J].Nanoscale,2018,10(44):20785-20795.
- [6] 李冉冉,徐忠金,王生轩,等.MEN1/Menin调控非酒精性脂肪肝的发生[J].农业生物技术学报,2019,27(12):2258-2264.
- [7] 李军汉,苏全生,孙君志,等.运动和饮食调整对内质网应激介导非酒精性脂肪肝大鼠模型肝细胞凋亡的影响[J].中国运动医学杂志,2017,36(1):36-43.
- [8] 潘磊,张金彪,崔荣岗,等.非酒精性脂肪肝C57BL/6小鼠模型的建立[J].中国组织工程研究,2016,20(40):6054-6059.
- [9] Maciejewska D,Lukomska A,Dec K,et al.Diet-induced rat model of gradual development of non-alcoholic fatty liver disease (NAFLD) with lipopolysaccharides (LPS) secretion[J].Diagnostics (Basel),2019,9(4):27-30.
- [10] 方婉军,陈旭,凌文华,等.内质网应激参与蛋氨酸-胆碱缺乏饮食诱导的小鼠非酒精性脂肪肝的形成[J].中山大学学报:医学科学版,2017,38(4):505-511.
- [11] Du X,Cai C,Yao J,et al.Histone modifications in FASN modulated by sterol regulatory element-binding protein 1c and carbohydrate responsive-element binding protein under insulin stimulation are related to NAFLD[J].Biochem Biophys Res Commun,2017,483(1):409-417.
- [12] Sarna LK,Sid V,Wang P,et al.Tyrosol attenuates high fat diet-induced hepatic oxidative stress:potential involvement of cystathionine β-synthase and cystathionine γ-lyase[J].Lipids,2016,51(5):583-590.
- [13] Gomaraschi M,Fracanzani AL,Dongiovanni P,et al.Lipid accumulation impairs lysosomal acid lipase activity in hepatocytes:evidence in NAFLD patients and cell cultures[J].Biochim Biophys Acta Mol Cell Biol Lipids,2019,1864(12):15823-15828.
- [14] Saghazadeh-Dezfuli M,Fanaei H,Gharib-Naseri MK,et al.Antidiarrheal effect of sodium hydrosulfide in diabetic rats:in vitro and in vivo studies[J].Neurogastroenterol Motil,2018,30(10):13273-13275.
- [15] 王明琦,李正强.硫化氢在肿瘤中的研究现状[J].医学分子生物学杂志,2018,15(5):357-362.
- [16] Kim HJ,Cho HJ,Kim B,et al.Accuracy and precision of proton density fat fraction measurement across field strengths and scan intervals:a phantom and human study[J].J Magn Reson Imaging,2019,50(1):305-314.
- [17] Li M,Xu C,Shi J,et al.Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfur transferase/hydrogen sulfide pathway[J].Gut,2018,67(12):2169-2180.
- [18] Chang TC,Chiang H,Lai YH,et al.Helminthostachys zeylanica alleviates hepatic steatosis and insulin resistance in diet-induced obese mice[J].BMC Complement Altern Med,2019,19(1):368-371.