及己根、茎、叶醇提取物的心脏毒性和毒性机制
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摘要
目的比较及己根、茎、叶醇提取物对大鼠心脏毒性的差异,初步探讨其毒性机制。方法将大鼠随机分成空白组、根醇组、茎醇组和叶醇组,每组8只。连续灌胃给药14d后,绘制体质量变化曲线,计算心脏系数,检测各组大鼠血清中肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(lactate dehydrogenase,LDH)和α-羟丁酸脱氢酶(α-hydroxybutyrate dehydrogenase,α-HBDH)的含量及心脏组织中氧化应激指标[总超氧化物歧化酶(total superoxide dismutase,T-SOD)和丙二醛(malondialdehyde,MDA)]的含量变化,观察各组大鼠心脏的组织病理学改变,检测心肌组织中细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、血红素加氧酶-1(heme oxygenase-1,HO-1)的表达。结果体质量增长率为茎醇组最小,其次为叶醇组。心脏系数在各组间差异均无统计学意义(P>0.05)。茎醇组心肌组织损伤程度最严重,其次为叶醇组。茎醇组CK、CK-MB、LDH、α-HBDH含量均升高(P<0.05)。与空白组和根醇组相比,茎醇组MDA含量升高,T-SOD含量降低,叶醇组仅T-SOD含量较空白组降低(P<0.05)。不同提取物干预后,ICAM-1阳性表达均增强,HO-1蛋白表达均降低,变化趋势为茎醇组>叶醇组>根醇组。结论及己茎醇提取物的心脏毒性最大,其次为叶醇提取物,其毒性机制可能与氧化应激有关。
Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH) and α-hydroxybutyrate dehydrogenase(α-HBDH) as well as the content changes of oxidative stress indexes — total superoxide dismutase(TSOD) and malondialdehyde(MDA) in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule(ICAM-1) and heme oxygenase(HO-1) in myocardial tissue was detected. Results Body mass growth rate:stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance(P>0.05). The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB,LDH and α-HBDH in stem alcohol group increased(P<0.05). The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group(P<0.05). The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.
Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH) and α-hydroxybutyrate dehydrogenase(α-HBDH) as well as the content changes of oxidative stress indexes — total superoxide dismutase(TSOD) and malondialdehyde(MDA) in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule(ICAM-1) and heme oxygenase(HO-1) in myocardial tissue was detected. Results Body mass growth rate:stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance(P>0.05). The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB,LDH and α-HBDH in stem alcohol group increased(P<0.05). The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group(P<0.05). The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.
引文
[1]江苏新医学院.中药大辞典(上册)[M].上海:上海科学技术出版社,1986:234.
[2]周寰远,胡隆隆.中药及己中毒致死1例[J].中国中西医结合杂志,1996,16(2):110.
[3]张毓锵,马世明,陈德良,等.及己中毒鉴定1例[J].中国法医学杂志,2010,25(2):133.
[4]ZHANG M,WANG J,LUO J,et al.Labdane diterpenes from Chloranthus serratus[J].Fitoterapia,2013,91:95-99.
[5]魏伟,吴希美,李元建.药理实验方法学[M].4版.北京:人民卫生出版社,2010:1698.
[6]王丽苹,沈志滨,唐春萍.中药有效成分对心肌细胞毒性作用机制的研究进展[J].广东药科大学学报,2018,34(2):249-253.
[7]EL-AGAMY D S,ABO-HADED H M,ELK-ABLAWY M A.Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats[J].Exp Biol Med(Maywood),2016,241(14):1577-1587.
[8]GOYAL S N,MAHAJAN U B,CHANDRAYANG,et al.Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats[J].Am J Transl Res,2016,8(1):60-69.
[9]ZHAO P,LI F,GAO W,et al.Angiotensin1-7protects cardiomyocytes from hypoxia/reoxygenationinduced oxidative stress by preventing ROS-associated mitochondrial dysfunction and activating the Akt signaling pathway[J].Acta Histochem,2015,117(8):803-810.
[10]NIKI E.Lipid peroxidation products as oxidative stress biomarkers[J].Biofactors,2008,34(2):171-180.
[11]ADAMIAK M,MOORE JBⅣ,ZHAO J,et al.Downregulation of heme oxygenase 1(HO-1)activity in hematopoietic cells enhances their engraftment after transplantation[J].Cell Transplant,2016,25(7):1265-1276.
[12]陈吉炎,王雪芹,李聪,等.及己与类似品的本草考证[J].现代中药研究与实践,2012,26(4):76-79.
[13]陈芳有,陈俊杰,周健,等.及己根的化学成分研究[J].中草药,2015,46(20):3004-3008.
[14]滕菲.及己和多穗金粟兰化学成分的研究[D].青岛:青岛科技大学,2009.
[15]孙淑萍,李胜利.及己根醇提物抗炎作用的研究[J].中国中医药现代远程教育,2013,11(7):149-150.
[2]周寰远,胡隆隆.中药及己中毒致死1例[J].中国中西医结合杂志,1996,16(2):110.
[3]张毓锵,马世明,陈德良,等.及己中毒鉴定1例[J].中国法医学杂志,2010,25(2):133.
[4]ZHANG M,WANG J,LUO J,et al.Labdane diterpenes from Chloranthus serratus[J].Fitoterapia,2013,91:95-99.
[5]魏伟,吴希美,李元建.药理实验方法学[M].4版.北京:人民卫生出版社,2010:1698.
[6]王丽苹,沈志滨,唐春萍.中药有效成分对心肌细胞毒性作用机制的研究进展[J].广东药科大学学报,2018,34(2):249-253.
[7]EL-AGAMY D S,ABO-HADED H M,ELK-ABLAWY M A.Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats[J].Exp Biol Med(Maywood),2016,241(14):1577-1587.
[8]GOYAL S N,MAHAJAN U B,CHANDRAYANG,et al.Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats[J].Am J Transl Res,2016,8(1):60-69.
[9]ZHAO P,LI F,GAO W,et al.Angiotensin1-7protects cardiomyocytes from hypoxia/reoxygenationinduced oxidative stress by preventing ROS-associated mitochondrial dysfunction and activating the Akt signaling pathway[J].Acta Histochem,2015,117(8):803-810.
[10]NIKI E.Lipid peroxidation products as oxidative stress biomarkers[J].Biofactors,2008,34(2):171-180.
[11]ADAMIAK M,MOORE JBⅣ,ZHAO J,et al.Downregulation of heme oxygenase 1(HO-1)activity in hematopoietic cells enhances their engraftment after transplantation[J].Cell Transplant,2016,25(7):1265-1276.
[12]陈吉炎,王雪芹,李聪,等.及己与类似品的本草考证[J].现代中药研究与实践,2012,26(4):76-79.
[13]陈芳有,陈俊杰,周健,等.及己根的化学成分研究[J].中草药,2015,46(20):3004-3008.
[14]滕菲.及己和多穗金粟兰化学成分的研究[D].青岛:青岛科技大学,2009.
[15]孙淑萍,李胜利.及己根醇提物抗炎作用的研究[J].中国中医药现代远程教育,2013,11(7):149-150.