枸杞多糖通过调控PI3K/Akt/eNOS信号通路对去卵巢大鼠心肌产生抗氧化作用
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摘要
目的:观察枸杞多糖对去卵巢大鼠心肌PI3K/Akt/e NOS信号通路的影响。方法:将30只SD雌性大鼠随机分为假手术组、去卵巢组、补佳乐组、枸杞多糖高剂量组及枸杞多糖低剂量组,ELISA法比较各组血清雌激素、LDH及CK水平,检测心肌H_2S含量及氧化应激损伤相关指标,HE染色观察各组心肌的形态变化,Western blot法检测各组大鼠心肌e NOS蛋白及PI3K/Akt通路蛋白的表达。结果:与假手术组相比,去卵巢组大鼠血清雌二醇水平降低,心肌H_2S含量和GSH-Px活性下降,心肌e NOS蛋白及PI3K/Akt通路蛋白的表达均有所降低,心肌ROS活性和MDA含量升高(P<0.05),心肌细胞排列紊乱,细胞间隙增大,血清LDH和CK活性均增多;与去卵巢组比较,枸杞多糖高剂量组大鼠血清雌二醇含量增加(P<0.05),心肌H_2S含量、GSH-Px活性、e NOS蛋白及Akt磷酸化水平均提高,心肌ROS活性和MDA含量下降(P<0.05),血清LDH和CK活性均降低,并且改善大鼠心肌形态的变化。结论:枸杞多糖可以通过调控PI3K/Akt/e NOS通路改善去卵巢大鼠心脏变化防治绝经后心血管病变。
AIM: To observe the influence of Lycium barbarum polysaccharide(LBP) on the PI3K/Akt/e NOS signaling pathways in ovariectomized rat myocardium. METHODS: Female SD rats( n = 30) were divided into sham operation group,ovariectomized group,progynova group,high-dose LBP group and low-dose LBP group. The serum levels of estradiol,lactate dehydrogenase( LDH) and creatine kinase( CK) were measured by ELISA. The myocardial contents of H_2 S and oxidative stress injury-related indicators were also detected. The morphological changes of the myocardium were observed with HE staining. The expression of e NOS and PI3 K / Akt pathway-related proteins in the myocardium was determined by Western blot. RESULTS: Compared with sham operation group,the serum level of estradiol,the content of H_2 S,the activity of GSH-Px,and the expression of e NOS and PI3 K / Akt pathway-related proteins in the myocardium in ovariectomized group were all decreased,and the levels of ROS and MDA in the myocardium were increased( P < 0. 05).The serum levels of LDH and CK were also increased. The arrangement of the myocardial cells was disordered,and the intercellular space was also increased in the ovariectomized group. Compared with ovariectomized group,the serum level of estradiol,the myocardial levels of H2 S and GSH-Px,and the protein levels of e NOS and phosphorylated Akt were all increased in high dose group,while the levels of ROS and MDA in the myocardium were decreased( P < 0. 05). The serum levels of LDH and CK were also decreased. The morphological changes of the rat myocardium were improved in high dose group. CONCLUSION: LBP prevents and treats postmenopausal cardiovascular lesions through regulating PI3 K / Akt /e NOS signaling pathways in ovariectomized rats.
AIM: To observe the influence of Lycium barbarum polysaccharide(LBP) on the PI3K/Akt/e NOS signaling pathways in ovariectomized rat myocardium. METHODS: Female SD rats( n = 30) were divided into sham operation group,ovariectomized group,progynova group,high-dose LBP group and low-dose LBP group. The serum levels of estradiol,lactate dehydrogenase( LDH) and creatine kinase( CK) were measured by ELISA. The myocardial contents of H_2 S and oxidative stress injury-related indicators were also detected. The morphological changes of the myocardium were observed with HE staining. The expression of e NOS and PI3 K / Akt pathway-related proteins in the myocardium was determined by Western blot. RESULTS: Compared with sham operation group,the serum level of estradiol,the content of H_2 S,the activity of GSH-Px,and the expression of e NOS and PI3 K / Akt pathway-related proteins in the myocardium in ovariectomized group were all decreased,and the levels of ROS and MDA in the myocardium were increased( P < 0. 05).The serum levels of LDH and CK were also increased. The arrangement of the myocardial cells was disordered,and the intercellular space was also increased in the ovariectomized group. Compared with ovariectomized group,the serum level of estradiol,the myocardial levels of H2 S and GSH-Px,and the protein levels of e NOS and phosphorylated Akt were all increased in high dose group,while the levels of ROS and MDA in the myocardium were decreased( P < 0. 05). The serum levels of LDH and CK were also decreased. The morphological changes of the rat myocardium were improved in high dose group. CONCLUSION: LBP prevents and treats postmenopausal cardiovascular lesions through regulating PI3 K / Akt /e NOS signaling pathways in ovariectomized rats.
引文
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[11]Node K,Kitakaze M,Kosaka H,et al.Amelioration of ischemia-and reperfusion-induced myocardial injury by17β-estradiol:role of nitric oxide and calcium-activized potassium channels[J].Circulation,1997,96(6):1953-1963.
[12]Beer S,Reincke M,Kral M,et al.Susceptibility to cardiac ischemia/reperfusion injury is modulated by chronic estrogen status[J].J Cardiovasc Pharmacol,2002,40(3):420-428.
[13]Pan TT,Feng ZN,Lee SW,et al.Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes[J].J Mol Cell Cardiol,2006,40(1):119-130.
[14]Giordano FJ.Oxygen,oxidative stress,hypoxia,and heart failure[J].J Clin Invest,2005,115(3):500-508.
[15]谢书阳,杨玲玲,陈浩,等.Aβ和氧自由基诱导的培养神经元凋亡及维生素E的保护作用[J].中国老年学杂志,2005,25(4):436-438.
[16]李政媛,张婷婷,陈宇豪,等.VE对去卵巢大鼠血清TSOD、GSH-Px活力与心肌细胞凋亡的影响[J].吉林医药学院学报,2009,30(3):133-135.
[17]Matsui T,Tao J,del Monte F,et al.Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo[J].Circulation,2001,104(3):330-335.
[18]董曦,孙桂波,罗云,等.间充质干细胞条件培养基激活Nrf2/ARE通路对抗H2O2致H9c2细胞的氧化应激损伤[J].中国病理生理杂志,2015,31(6):961-966.
[19]储佳佳,李积东,雷霖,等.柚皮苷对高糖诱导的血管内皮细胞损伤及PI3K/Akt/e NOS信号通路的影响[J].中国病理生理杂志,2015,31(4):625-629.
[2]林莉芬.小剂量雌激素治疗围绝经期综合征疗效分析[J].药物与临床,2012,19(6):65-67.
[3]闫丹,阮祥燕.不同雌孕激素对绝经妇女心血管影响的研究进展[J].中国药学杂志,2011,46(9):646-648.
[4]田秀娟,盛敏佳,刘俊宝,等.激素替代治疗对绝经后女性心脑血管疾病的影响[J].中国老年学杂志,2009,29(18):2376-2377.
[5]Ferrari R,Agnoletti L,Comini L,et al.Oxidative stress during myocardial ischaemia and heart failure[J].Eur Heart J,1998,19(Suppl B):B2-B11.
[6]Xin YF,Wana LL,Peng JL,et al.Alleviation of the acute doxorubicin-induced cardiotoxicity by Lycium barbarum polysaccharides through the suppression of oxidative stress[J].Food Chem Toxicol,2011,49(1):259-264.
[7]Yong QC,Lee SW,Foo CS,et al.Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning[J].Am J Physiol Heart Circ Physiol,2008,295(3):H1330-H1340.
[8]Nelson HD,Humphrey LL,Nygren P,et al.Postmenopausal hormone replacement therapy:scientific review[J].JAMA,2002,288(7):872-881.
[9]Babiker FA,De Windt LJ,van Eickels M,et al.Estrogenic hormone action in the heart:regulatory network and function[J].Cardiovasc Res,2002,53(3):709-719.
[10]Yildirir A,Yarali H,Aybar F,et al.Hormone replacement therapy to improve left ventricular diastolic functionsin healthy postmenopausal women[J].Int J Gynaecol Obstet,2001,75(3):273-278.
[11]Node K,Kitakaze M,Kosaka H,et al.Amelioration of ischemia-and reperfusion-induced myocardial injury by17β-estradiol:role of nitric oxide and calcium-activized potassium channels[J].Circulation,1997,96(6):1953-1963.
[12]Beer S,Reincke M,Kral M,et al.Susceptibility to cardiac ischemia/reperfusion injury is modulated by chronic estrogen status[J].J Cardiovasc Pharmacol,2002,40(3):420-428.
[13]Pan TT,Feng ZN,Lee SW,et al.Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes[J].J Mol Cell Cardiol,2006,40(1):119-130.
[14]Giordano FJ.Oxygen,oxidative stress,hypoxia,and heart failure[J].J Clin Invest,2005,115(3):500-508.
[15]谢书阳,杨玲玲,陈浩,等.Aβ和氧自由基诱导的培养神经元凋亡及维生素E的保护作用[J].中国老年学杂志,2005,25(4):436-438.
[16]李政媛,张婷婷,陈宇豪,等.VE对去卵巢大鼠血清TSOD、GSH-Px活力与心肌细胞凋亡的影响[J].吉林医药学院学报,2009,30(3):133-135.
[17]Matsui T,Tao J,del Monte F,et al.Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo[J].Circulation,2001,104(3):330-335.
[18]董曦,孙桂波,罗云,等.间充质干细胞条件培养基激活Nrf2/ARE通路对抗H2O2致H9c2细胞的氧化应激损伤[J].中国病理生理杂志,2015,31(6):961-966.
[19]储佳佳,李积东,雷霖,等.柚皮苷对高糖诱导的血管内皮细胞损伤及PI3K/Akt/e NOS信号通路的影响[J].中国病理生理杂志,2015,31(4):625-629.