葱白提取物对非酒精性脂肪肝模型大鼠PGC-1α和线粒体生物合成的影响
摘要
目的观察葱白提取物对非酒精性脂肪肝(NAFLD)模型大鼠PGC-1α、核呼吸因子1(nuclear respiratory factor 1,NRF-1)、线粒体转录因子A(transcription factor A,TFAM)表达的影响,并探讨其作用机制。方法采用高脂饲料复制非酒精性脂肪肝大鼠模型,并应用小干扰RNA(SiRNA)技术抑制过氧化物酶体增殖物激活受体γ辅助激活因子-1α(peroxisome proliferator activated receptor-γcoactivator 1α,PGC-1α)的表达。将48只SD大鼠随机分为正常组、模型组、葱白组、转染组、空转组、转染加葱白组。光镜下观察肝组织HE染色组织结构;检测血清AST、ALT、TC、TG水平; Realtime PCR和Western-blot分别检测大鼠肝脏PGC-1αmRNA及PGC-1α、NRF-1、TFAM蛋白质的表达。结果模型组出现明显肝脏脂肪变性;血清ALT、AST、TC、TG水平也高于正常组(P <0. 05);相较于模型组,葱白组肝内脂肪变性明显减轻;血清ALT、AST、TC、TG水平均降低(P <0. 05)。PGC-1α、NRF-1、TFAM表达情况:与正常组比较,模型组的PGC-1α和NRF-1、TFAM蛋白的表达明显降低(P <0. 05);与模型组比较,葱白组的PGC-1α和NRF-1、TFAM蛋白表达升高(P <0. 05);与空转组比较,转染组的PGC-1α和NRF-1、TFAM蛋白表达水平下降(P <0. 05);与葱白组比较,转染加葱白组的PGC-1α和NRF-1、TFAM蛋白表达水平下降(P <0. 05)。结论辛温通阳中药葱白提取物可能通过提高PGC-1α的转录活化水平,促进NRF-1、TFAM的表达从而促进肝线粒体生物合成改善肝脂肪变性。
引文
[1] Yatsuji S,Hashimoto E,Kaneda H,et al. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease:is the International Autoimmune Hepatitis Group scoring system useful[J]. J Gastroenterol,2005,40(12):1130.
[2] Forbes S,Taylorrobinson S D,Patel N,et al. Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes[J]. Diabetologia,2011,54(3):641.
[3]郭洁,赵蕾,毛叶登,等.葱白提取物对非酒精性脂肪肝模型大鼠PGC-1α和脂肪酸β氧化限速酶CPT-1表达的影响[J].时珍国医国药,2016,27(7):1581.
[4]许思思,时昭红,郭洁.葱白提取物调节非酒精性脂肪肝脂质水平的机制研究[J].医学信息,2016,29(36):44.
[5]时昭红,张介眉,郑娅琼,等.鲜葱白提取物对实验性非酒精性脂肪肝的药效作用[J].现代消化及介入诊疗,2009,14(3):137.
[6]樊丽琳,陈东风.肝脏线粒体呼吸功能损伤在大鼠非酒精性脂肪性肝病中的作用[J].重庆医学,2007,36(15):1503.
[7]丁晓东,范建高,徐正婕,等.高脂饮食性脂肪性肝炎大鼠肝脏线粒体损伤和ATP储备改变[J].世界华人消化杂志,2005,13(13):1524.
[8] Nisoli E,Clementi E,Paolucci C,et al. Mitochondrial biogenesis in mammals:the role of endogenous nitric oxide[J]. Science,2003,299(5608):896.
[9] Cannon B,Nedergaard J. Brown adipose tissue:function and physiological significance.[J]. Physiol Rev,2004,84(1):277.
[10] Day C P. Pathogenesis of steatohepatitis[J]. Best Pract Res Clin Gastroenterol,2002,16(5):663.
[11] Short K R,Vittone J L,Bigelow M L,et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity[J]. Diabetes,2003,52(8):1888.
[12] Wu Z,Boss O. Targeting PGC-1αto control energy homeostasis[J].Expert Opin Ther Targets,2007,11(10):1329.
[13]牟彩莹,王松. PGC-1α对线粒体生物合成功能的调控[J].四川解剖学杂志,2011,19(1):36.
[14] Choi Y S,Kim S,Kyu L H,et al. In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A[J]. Biochem Biophys Res Commun,2004,314(1):118.
[15]郝建军,张介眉,时昭红,等.张介眉教授运用“通阳法”异病同治的临床和实验研究[C].第二十四届全国中西医结合消化系统疾病学术会议专题报告及论文集,2012.
[16]户菲菲,张介眉,郝建军.痰瘀交阻与通阳[J].天津中医药,2010,27(4):303.
[17]户菲菲,张介眉,朱旭,等.通阳药葱白提取物对肝窦毛细血管化大鼠肝组织Ⅳ型胶原的影响[J].中西医结合肝病杂志,2010,20(1):32.
[18]户菲菲,张介眉,朱旭,等.通阳药葱白提取物对肝窦毛细血管化大鼠肝组织MMP-2,TIMP-2蛋白及mRNA表达影响的研究[J].成都中医药大学学报,2010,33(4):55.
[2] Forbes S,Taylorrobinson S D,Patel N,et al. Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes[J]. Diabetologia,2011,54(3):641.
[3]郭洁,赵蕾,毛叶登,等.葱白提取物对非酒精性脂肪肝模型大鼠PGC-1α和脂肪酸β氧化限速酶CPT-1表达的影响[J].时珍国医国药,2016,27(7):1581.
[4]许思思,时昭红,郭洁.葱白提取物调节非酒精性脂肪肝脂质水平的机制研究[J].医学信息,2016,29(36):44.
[5]时昭红,张介眉,郑娅琼,等.鲜葱白提取物对实验性非酒精性脂肪肝的药效作用[J].现代消化及介入诊疗,2009,14(3):137.
[6]樊丽琳,陈东风.肝脏线粒体呼吸功能损伤在大鼠非酒精性脂肪性肝病中的作用[J].重庆医学,2007,36(15):1503.
[7]丁晓东,范建高,徐正婕,等.高脂饮食性脂肪性肝炎大鼠肝脏线粒体损伤和ATP储备改变[J].世界华人消化杂志,2005,13(13):1524.
[8] Nisoli E,Clementi E,Paolucci C,et al. Mitochondrial biogenesis in mammals:the role of endogenous nitric oxide[J]. Science,2003,299(5608):896.
[9] Cannon B,Nedergaard J. Brown adipose tissue:function and physiological significance.[J]. Physiol Rev,2004,84(1):277.
[10] Day C P. Pathogenesis of steatohepatitis[J]. Best Pract Res Clin Gastroenterol,2002,16(5):663.
[11] Short K R,Vittone J L,Bigelow M L,et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity[J]. Diabetes,2003,52(8):1888.
[12] Wu Z,Boss O. Targeting PGC-1αto control energy homeostasis[J].Expert Opin Ther Targets,2007,11(10):1329.
[13]牟彩莹,王松. PGC-1α对线粒体生物合成功能的调控[J].四川解剖学杂志,2011,19(1):36.
[14] Choi Y S,Kim S,Kyu L H,et al. In vitro methylation of nuclear respiratory factor-1 binding site suppresses the promoter activity of mitochondrial transcription factor A[J]. Biochem Biophys Res Commun,2004,314(1):118.
[15]郝建军,张介眉,时昭红,等.张介眉教授运用“通阳法”异病同治的临床和实验研究[C].第二十四届全国中西医结合消化系统疾病学术会议专题报告及论文集,2012.
[16]户菲菲,张介眉,郝建军.痰瘀交阻与通阳[J].天津中医药,2010,27(4):303.
[17]户菲菲,张介眉,朱旭,等.通阳药葱白提取物对肝窦毛细血管化大鼠肝组织Ⅳ型胶原的影响[J].中西医结合肝病杂志,2010,20(1):32.
[18]户菲菲,张介眉,朱旭,等.通阳药葱白提取物对肝窦毛细血管化大鼠肝组织MMP-2,TIMP-2蛋白及mRNA表达影响的研究[J].成都中医药大学学报,2010,33(4):55.