野芭蕉多糖对自发性高血压大鼠血管平滑肌细胞增殖的影响及其与胆固醇调节元件结合蛋白表达的关系
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摘要
目的:探讨野芭蕉多糖对自发性高血压大鼠(SHR)血管平滑肌细胞(VSMC)增殖的抑制作用及其与胆固醇调节元件结合蛋白(SREBP)的关系。方法:分离SHR VSMC传代培养取得VSMC系后,分成4组:高、中、低浓度组(0.01、0.1、1.0μmol/L野芭蕉多糖)和对照组(纯化水),用第4代VSMC进行药物干预培养,于干预培养24、48、100、120h,分别检测VSMC细胞活力及增殖周期,取干预培养100h的标本检测SREBP mRNA相对表达量,并与对照组比较。结果:与对照组比较,中、高浓度野芭蕉多糖组VSMC细胞增殖率显著降低(P<0.01),增殖周期(G0+G1期)显著延长(P<0.01),SREBP mRNA相对表达量受到显著抑制(P<0.01)。药理效应与剂量呈正相关关系。结论:野芭蕉多糖可有效抑制SHR VSMC的过度增殖,其作用机制可能与下调SREBP mRNA表达、调节脂质代谢紊乱有关。
Objective: To study the inhibitory effect of Musa balbisiana polysaccharide on proliferation of vascular smooth muscle cells(VSMC) in SHR rats and their relationship with sterol regulating element binding protein(SREBP). Methods:Separation collaterals disease rat VSMC of subculture, VSMC medium could be divided into four groups: high-dose, mediumdose and low-dose groups and control group giving, the concentration of 0.01, 0.1, 1.0μmol/L and water for injection, with the fourth generation of VSMC drug intervention, the intervention training 24 h, 48 h, 100 h and 120 h specimen, VSMC proliferation rate was detected in proliferation cycle, take intervention training samples sterol regulation of 100 h element binding protein SREBP mRNA expression of relative quantity, and compared with the control group. Results: Compared with the control group,the proliferation rate of VSMC cells in the medium-dose, high-dose, group decrease(P<0.01), and the proliferation cycle(G0+G1)was prolonged(P<0.01), and the relative expression of SREBP mRNA was inhibited(P<0.01). The pharmacological effect and the dose relationship. Conclusion: Musa balbisiana polysaccharide can effectively inhibit the excessive proliferation of VSMC in the rats, and its mechanism may be related to down-regulation of SREBP mRNA expression and regulation of lipid metabolism disorder.
Objective: To study the inhibitory effect of Musa balbisiana polysaccharide on proliferation of vascular smooth muscle cells(VSMC) in SHR rats and their relationship with sterol regulating element binding protein(SREBP). Methods:Separation collaterals disease rat VSMC of subculture, VSMC medium could be divided into four groups: high-dose, mediumdose and low-dose groups and control group giving, the concentration of 0.01, 0.1, 1.0μmol/L and water for injection, with the fourth generation of VSMC drug intervention, the intervention training 24 h, 48 h, 100 h and 120 h specimen, VSMC proliferation rate was detected in proliferation cycle, take intervention training samples sterol regulation of 100 h element binding protein SREBP mRNA expression of relative quantity, and compared with the control group. Results: Compared with the control group,the proliferation rate of VSMC cells in the medium-dose, high-dose, group decrease(P<0.01), and the proliferation cycle(G0+G1)was prolonged(P<0.01), and the relative expression of SREBP mRNA was inhibited(P<0.01). The pharmacological effect and the dose relationship. Conclusion: Musa balbisiana polysaccharide can effectively inhibit the excessive proliferation of VSMC in the rats, and its mechanism may be related to down-regulation of SREBP mRNA expression and regulation of lipid metabolism disorder.
引文
[1]Monnerie H,Romer M,Jensen B K,et al.Reduced sterol regulatory element-binding protein(SREBP)processing through site-1protease(S1P)inhibition alters oligodendrocyte differentiation in vitro.J Neurochem,2017,140(1):53-67
[2]梁烨,李天资,陆高翔,等.野芭蕉治疗自发性高血压大鼠疗效机理的实验研究.时珍国医国药,2013,24(10):2324-2326
[3]Seo K,Shin S M.Induction of Lipin1 by ROS-dependent SREBP-2activation.Toxicol Res,2017,33(3):219-224
[4]樊凯芳,王欢,刘其.当归四逆汤对血管平滑肌细胞增殖及迁移的影响.中华中医药杂志,2018,33(8):3375-3379
[5]韦彤雁,李近都.腔隙性脑梗死中医理论及其野芭蕉治疗研究进展.中西医结合心脑血管病杂志,2013,11(9):1109-1110
[6]梁烨,李天资,陆高翔,等.野芭蕉通络汤对改善高血压患者氧化应激功能紊乱疗效观察.中华中医药杂志,2012,27(7):1967-1969
[7]李天资,梁烨,陆高翔,等.野芭蕉治疗高血压颈动脉斑块阳性患者疗效机制的临床研究.时珍国医国药,2012,23(9):2259-2260
[8]杨萃,袁卓,张军平.四妙勇安汤对血管平滑肌细胞迁移的影响.中华中医药杂志,2013,28(5):1480-1483
[9]Ren R,Gong J,Zhao Y,et al.Ulfated polysaccharides from enteromorpha prolifera suppress SREBP-2 and HMG-CoAreductase expression and attenuate non-alcoholic fatty liver disease induced by a high-fat diet.Food Funct,2017,8(5):1899-1904
[10]Miao J,Haas J T,Manthena P,et al.Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins.J Lipid Res,2014,55(4):659-667
[11]Aylon Y,Gershoni A,Rotkopf R,et al.The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.Genes Dev,2016,30(7):786-797
[12]Siculella L,Tocci R,Rochira A,et al.Lipid accumulation stimulates the cap-independent translation of SREBP-1a mRNA by promoting hn RNP A1 binding to its 5’-UTR in a cellular model of hepatic steatosis.Biochim Biophys Acta,2016,1861(5):471-481
[13]Vergnes L,Chin R G,de Aguiar Vallim T,et al.SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression.J Lipid Res,2016,57(3):410-421
[14]Tarling E J,Ahn H,de Aguiar Vallim T Q.The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2.Arterioscler Thromb Vasc Biol,2015,35(4):787-795
[15]董建勋,余胜,路广林,等.舒脉胶囊对血管紧张素Ⅱ诱导的血管平滑肌细胞增生及NO、SOD、MDA的影响.中华中医药杂志,2010,25(5):752-754
[16]Park J,Yeom M,Hahm D H.Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation.J Pharmacol Sci,2016,131(2):84-92
[17]凌福正,李近都,梁烨,等.超声波萃取野芭蕉总生物碱含量及其优化筛选.中国医药科学,2017,7(1):48-51
[18]江洪,梁烨,李近都,等.野芭蕉通络汤治疗对高血压患者miR-375调控的临床观察.中药药理与临床,2015,31(2):103-104
[19]潘兴寿,梁烨,李天资,等.野芭蕉辅助治疗高血压伴稳定劳力型心绞痛PCI术后患者炎症反应疗效观察.时珍国医国药,2014,25(9):2171-2173
[20]潘兴寿,何思陆,梁烨,等.地龙野芭蕉改善老年高血压伴腔隙性脑梗死患者纤溶内皮功能的临床观察.中国医药科学,2016,6(17):9-12,16
[2]梁烨,李天资,陆高翔,等.野芭蕉治疗自发性高血压大鼠疗效机理的实验研究.时珍国医国药,2013,24(10):2324-2326
[3]Seo K,Shin S M.Induction of Lipin1 by ROS-dependent SREBP-2activation.Toxicol Res,2017,33(3):219-224
[4]樊凯芳,王欢,刘其.当归四逆汤对血管平滑肌细胞增殖及迁移的影响.中华中医药杂志,2018,33(8):3375-3379
[5]韦彤雁,李近都.腔隙性脑梗死中医理论及其野芭蕉治疗研究进展.中西医结合心脑血管病杂志,2013,11(9):1109-1110
[6]梁烨,李天资,陆高翔,等.野芭蕉通络汤对改善高血压患者氧化应激功能紊乱疗效观察.中华中医药杂志,2012,27(7):1967-1969
[7]李天资,梁烨,陆高翔,等.野芭蕉治疗高血压颈动脉斑块阳性患者疗效机制的临床研究.时珍国医国药,2012,23(9):2259-2260
[8]杨萃,袁卓,张军平.四妙勇安汤对血管平滑肌细胞迁移的影响.中华中医药杂志,2013,28(5):1480-1483
[9]Ren R,Gong J,Zhao Y,et al.Ulfated polysaccharides from enteromorpha prolifera suppress SREBP-2 and HMG-CoAreductase expression and attenuate non-alcoholic fatty liver disease induced by a high-fat diet.Food Funct,2017,8(5):1899-1904
[10]Miao J,Haas J T,Manthena P,et al.Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins.J Lipid Res,2014,55(4):659-667
[11]Aylon Y,Gershoni A,Rotkopf R,et al.The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.Genes Dev,2016,30(7):786-797
[12]Siculella L,Tocci R,Rochira A,et al.Lipid accumulation stimulates the cap-independent translation of SREBP-1a mRNA by promoting hn RNP A1 binding to its 5’-UTR in a cellular model of hepatic steatosis.Biochim Biophys Acta,2016,1861(5):471-481
[13]Vergnes L,Chin R G,de Aguiar Vallim T,et al.SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression.J Lipid Res,2016,57(3):410-421
[14]Tarling E J,Ahn H,de Aguiar Vallim T Q.The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2.Arterioscler Thromb Vasc Biol,2015,35(4):787-795
[15]董建勋,余胜,路广林,等.舒脉胶囊对血管紧张素Ⅱ诱导的血管平滑肌细胞增生及NO、SOD、MDA的影响.中华中医药杂志,2010,25(5):752-754
[16]Park J,Yeom M,Hahm D H.Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation.J Pharmacol Sci,2016,131(2):84-92
[17]凌福正,李近都,梁烨,等.超声波萃取野芭蕉总生物碱含量及其优化筛选.中国医药科学,2017,7(1):48-51
[18]江洪,梁烨,李近都,等.野芭蕉通络汤治疗对高血压患者miR-375调控的临床观察.中药药理与临床,2015,31(2):103-104
[19]潘兴寿,梁烨,李天资,等.野芭蕉辅助治疗高血压伴稳定劳力型心绞痛PCI术后患者炎症反应疗效观察.时珍国医国药,2014,25(9):2171-2173
[20]潘兴寿,何思陆,梁烨,等.地龙野芭蕉改善老年高血压伴腔隙性脑梗死患者纤溶内皮功能的临床观察.中国医药科学,2016,6(17):9-12,16