罗汉果皂苷对阿霉素心肌损伤大鼠氧化应激和凋亡调节作用研究
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摘要
目的 :从氧化应激和凋亡途径研究罗汉果皂苷对阿霉素心肌损伤大鼠的治疗作用,以为罗汉果皂苷治疗阿霉素心肌损伤提供基础实验理论。方法 :60只清洁级雄性SD大鼠采用一次性尾静脉注射阿霉素18 mg/kg构建阿霉素心肌损伤模型,模型构建成功后按照随机数字法将其分为正常组,模型组以及罗汉果皂苷低、中和高剂量治疗组,每组12只,罗汉果皂苷治疗4周后,收集血清和心脏,检测心肌病理学、心功能、血清SOD和MDA,同时采用Western Blotting和实时荧光定量检测心肌组织中Bax、Bcl-2蛋白和mRNA的表达特点。结果 :HE染色可见正常组心肌纤维排列整齐,模型组则有明显的心肌排列紊乱,与模型组相比,罗汉果皂苷低、中和高剂量有不同程度的减轻;与正常组相比,模型组AST、LDH、CK-MB和MDA明显升高(P<0.05),罗汉果皂苷3个剂量组均可以明显降低上述几个指标(P<0.05);与正常组相比,模型组SOD明显降低(P<0.05),罗汉果皂苷3个剂量组相较于模型组则明显升高(P<0.05);与正常组相比,模型组Bax蛋白和mRNA明显升高(P<0.05),Bcl-2蛋白和mRNA明显降低(P<0.05),与模型组相比,罗汉果皂苷3个剂量组均可以降低Bax(P<0.05),同时升高Bcl-2表达(P<0.05)。结论 :罗汉果皂苷可增强阿霉素心肌损伤大鼠抗氧化能力,抑制心肌细胞凋亡,进而改善心功能。
Objective :To study the therapeutic effect of mogmside on oxidative and apoptotic in adriamycin myocardium injury rat,in order to provide a basic theory for mogmside treating myocardial injury. Methods :60 clean grade male SD rats were established myocardial injury model by treated with a single intravenous injection of adriamycin(18 mg/kg),after the model successful construction,they were divided into the normal group,model group,and mogmside low,medium and high dose treatment group according to the random number method,each group was 12 cases. After 4 weeks of treatment,serum and heart tissue were collected to detect myocardial pathology,heart function,serum SOD and MDA. Meanwhile,Western Blotting and real-time fluorescence quantitative detected the mRNA and proteins expression of Bax and Bcl-2 in myocardial tissue. Results :HE staining showed that the myocardial fibers in the normal group were well-arranged,while in the model group had significant myocardial disorder,compared with the model group,the low,medium,and high doses of mogmside had varying degrees improvement;compared with the normal group,the AST,LDH,CK-MB and MDA in the model group were significantly increased(P<0.05),and the content of the above-mentioned several indexes was significantly reduced in the three mogmside groups(P<0.05);Compared with the normal group,the SOD in the model was significantly lower(P<0.05),with the model group,SOD in the mogmside groups was significantly higher(P<0.05). Compared with the normal group,the Bax protein and mRNA expression in the model group were significantly higher(P<0.05). Bcl-2 protein and mRNA expression were significantly lower(P<0.05),compared with the model group,mogmside could reduce Bax expression(P<0.05),while increase Bcl-2 expression(P<0.05). Conclusion :Mogmside could enhance the anti-oxidation ability and inhibit cardiomyocyte apoptosis in rats with adriamycin-induced myocardial injury,further improve cardiac function.
Objective :To study the therapeutic effect of mogmside on oxidative and apoptotic in adriamycin myocardium injury rat,in order to provide a basic theory for mogmside treating myocardial injury. Methods :60 clean grade male SD rats were established myocardial injury model by treated with a single intravenous injection of adriamycin(18 mg/kg),after the model successful construction,they were divided into the normal group,model group,and mogmside low,medium and high dose treatment group according to the random number method,each group was 12 cases. After 4 weeks of treatment,serum and heart tissue were collected to detect myocardial pathology,heart function,serum SOD and MDA. Meanwhile,Western Blotting and real-time fluorescence quantitative detected the mRNA and proteins expression of Bax and Bcl-2 in myocardial tissue. Results :HE staining showed that the myocardial fibers in the normal group were well-arranged,while in the model group had significant myocardial disorder,compared with the model group,the low,medium,and high doses of mogmside had varying degrees improvement;compared with the normal group,the AST,LDH,CK-MB and MDA in the model group were significantly increased(P<0.05),and the content of the above-mentioned several indexes was significantly reduced in the three mogmside groups(P<0.05);Compared with the normal group,the SOD in the model was significantly lower(P<0.05),with the model group,SOD in the mogmside groups was significantly higher(P<0.05). Compared with the normal group,the Bax protein and mRNA expression in the model group were significantly higher(P<0.05). Bcl-2 protein and mRNA expression were significantly lower(P<0.05),compared with the model group,mogmside could reduce Bax expression(P<0.05),while increase Bcl-2 expression(P<0.05). Conclusion :Mogmside could enhance the anti-oxidation ability and inhibit cardiomyocyte apoptosis in rats with adriamycin-induced myocardial injury,further improve cardiac function.
引文
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[2]Aramvash A,Chadegani A R,Lotfi S. Evaluation of Apoptosis in Multipotent Hematopoietic Cells of Bone Marrow by Anthracycline Antibiotics[J]. Iranian Journal of Pharmaceutical Research Ijpr,2017,16(3):1204-1213.
[3]?tenglová-NetíkováI R,Petru?elka L,?tastnyM,et al.Anthracycline antibiotics derivate mitoxantrone-Destructive sorption and photocatalytic degradation[J]. Plos One,2018,13(3):e0193116.
[4]Shuykova K V,Emelina E I,Gendlin G E,et al. Change of the left ventricle functioning in lymphoma treated with anthracycline antibiotics[J]. Russian Journal of Cardiology,2016,129(1):41-46.
[5]赵文英,陈冬云,邢文,等.磷酸肌酸钠对小鼠阿霉素心肌损伤的保护机制初探[J].中国临床药理学与治疗学,2011,16(3):259-262.
[6]陶辉宇,李丽,陈杰斌,等.纳米α-亚麻酸对大鼠阿霉素心肌损伤的保护作用及其抗氧化机制研究[J].中国现代医学杂志,2006,16(13):1978-1982.
[7]苏丹,刘鹏飞,张柳,等.阿霉素心肌损伤大鼠模型的制备与评价[J].中国实验动物学报,2009,17(6):442-444.
[8]朱帅.阿霉素致心肌损伤大鼠模型的制备与评价[D].吉林:吉林大学,2014.
[9]金凯,陈中军,罗华荣.盐酸阿霉素对大鼠心肌损伤的分子机制研究[J].同济大学学报:医学版,2002,23(3):191-194.
[10]牛婷.自噬在阿霉素诱导小鼠心肌损伤中的作用机制[D].济南:山东大学,2013.
[11]万艳娟,吴军林,吴清平.罗汉果降血糖作用及机理研究进展[J].食品研究与开发,2016,37(11):188-191.
[12]曾祥林.广西特产植物罗汉果研究进展[J].广西医学,2009,31(8):1182-1186.
[13]陈瑶,贾恩礼.罗汉果化学成分和药理作用的研究进展[J].解放军药学学报,2011,27(2):171-174.
[14]张俐勤,戚向阳,陈维军,等.罗汉果皂苷提取物对糖尿病小鼠血糖、血脂及抗氧化作用的影响[J].中国药理学通报,2006,22(2):237-240.
[15]邹健,陈秋平,刘合生,等.罗汉果皂苷类化合物的抗氧化活性研究[J].核农学报,2016,30(10):1982-1988.
[16]王勤,王坤,戴盛明,等.罗汉果甜苷对小鼠细胞免疫功能的调节作用[J].中药材,2001,24(11):811-812.
[17]Martín-Fernández B,Gredilla R. Mitochondria and oxidative stress in heart aging[J]. Age,2016,38(4):1-14.
[18]Li B,Chi R,Qin F,et al. Distinct changes of myocyte autophagy during myocardial hypertrophy and heart failure:association with oxidative stress[J]. Experimental Physiology,2016,101(8):1050-1063.
[19]郭金栋.益气活血方对阿霉素心肌损伤大鼠SOD、MDA、CK-MB影响的实验研究[D].昆明:云南中医学院,2016.
[20]陆晓濛.黄芪对阿霉素诱导扩张型心肌病大鼠心肌细胞凋亡的影响[D].南京:南京中医药大学,2016.
[21]庄华梅,陈秀娇,林灿,等.参附汤对心脏毒性损伤大鼠细胞凋亡相关基因的影响[J].莆田学院学报,2016,23(2):10-14.
[22]Zhang W Z,Li R,Liu S,et al. Effects of Renal Ischemic Postconditioning on Myocardial Ultrastructural Organization and Myocardial Expression of Bcl-2/Bax in Rabbits[J]. Biomed Research International,2016,2016(5):1-10.
[23]Zhou S,Wang Y,Zhu J J. Simultaneous Detection of Tumor Cell Apoptosis Regulators Bcl-2 and Bax through a Dual-SignalMarked Electrochemical Immunosensor[J]. Acs Appl Mater Interfaces,2016,8(12):7674-7682.