麦粒灸对阿霉素心肌病大鼠硫化氢信号分子的影响

肖燕; 丁亮; 陈昊; 顾一煌

麦粒灸对阿霉素心肌病大鼠硫化氢信号分子的影响

肖燕¹,
丁亮²,
陈昊¹,
顾一煌^1,

1.
南京中医药大学第二临床医学院，江苏南京 210023
2.
南京中医药大学中医药文献研究所，江苏南京 210023

计量
- 文章访问数: 916
- HTML全文浏览量: 2
- PDF下载量: 1059
- 被引次数: 0
出版历程
- 收稿日期: 2015-11-25
- 修回日期: 2016-01-15
- 刊出日期: 2016-09-10

Effects of Grain-Moxibustion on Signaling Molecule of Hydrogen Sulfide in Adriamycin-Induced Cardiomyopathy Rats

1.
The Second Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
2.
Literature Research Institute, Nanjing University of Chinese Medicine, Nanjing, 210023, China

摘要

摘要: 目的观察麦粒灸对阿霉素(Adriamycin，ADR）心肌毒性的抑制效应，从内源性硫化氢（H₂S）角度探讨麦粒灸对ADR心肌毒性的可能机制。方法将30只SPF级SD大鼠随机分为空白对照组、模型组和麦粒灸组，每组10只。模型组及麦粒灸组尾静脉注射ADR制备心肌毒性模型；空白组尾静脉注射等量的0.9%NaCl溶液，不施灸；麦粒灸组在给药造模的同时取关元、巨阙穴进行麦粒灸治疗，每穴灸5壮，每日1次，每周休息2 d，持续4周。末次干预结束后检测大鼠心率（HR）、左室收缩压（LVSP）、左室舒张压（LVDP）、左室内压最大上升速率（+dp/dt_max）、左室内压最大下降速率（-dp/dt_max）、左室内压变化时间（t-dp/dt_max）；取各组大鼠血清及心脏，测定血清乳酸脱氢酶（LDH）、磷酸肌酸激酶（CK）、心肌肌钙蛋白I（cTnI）及心肌组织中硫化氢（H₂S）含量，评估大鼠心功能。制备大鼠心肌组织切片，观察大鼠心肌形态学变化。结果与空白组和麦粒灸组比较，模型组HR、LVSP、+dp/dt_max、 -dp/dt_max降低（P<0.05），LVDP和t-dp/dt_max升高（P<0.05）。与空白组比较，模型组大鼠血清LDH、CK酶活性及cTnI表达水平升高（P<0.05），心肌组织H₂S含量降低（P<0.05）；与模型组比较，麦粒灸组大鼠血清LDH、CK酶活性及cTnI表达水平降低（P<0.05），心肌组织中的H₂S含量升高（P<0.05）。光镜下，空白对照组心肌细胞结构完整、无心肌破坏，细胞间隙正常，无病变发生；模型组心肌组织细胞肿胀、充血、排列紊乱；麦粒灸组心肌细胞充血肿胀情况则较模型组轻，心肌细胞轻微肿胀、出血。结论麦粒灸可改善ADR引起的心功能异常，减轻ADR引起的心肌细胞肿胀、充血。其机制可能与麦粒灸调控内源性H₂S的生成，增加了内源性H₂S的含量，最终调控以H₂S为介导的各种信号通路发挥心肌保护效应有关。
- 阿霉素 /
- 心肌毒性 /
- 麦粒灸 /
- 硫化氢
Abstract: OBJECTIVE To observe the inhibitory effect of grain-moxibustion on ADR-induced cardiotoxicity， and explore the possible mechanism from the perspective of endogenous hydrogen sulfide (H₂S). METHODS 30 SPF-grade SD rats were randomly divided into blank control group， model group and grain-moxibustion group， 10 cases in each one. Rats in the model group and the grain-moxibustion group were treated with tail vein of ADR to establish the ADR-induced cardiotoxicity models. Rats in the blank group were treated with an equal amount of saline. Rats in the grain-moxibustion group were treated with grain-moxibustion at a same time of dosing building every day at Guanyuan(CV4) and Juque(CV14)， 5 cones at each acupoint， once daily for 4 weeks，2 d of rest per week. At the end of the last intervention， we detected HR， LVSP)， LVDP， +dp/dt_max， -dp/dt_max and t-dp/dt_max. Serum were collected to test the activities of LDH and CK and the content of cTnI， and myocardium tissue were collected to measure the content of H₂S， to make a comprehensive assessment of the cardiac function in rats. Myocardial tissue biopsies were prepared to observe the morphological changes of myocardial pathology organization. RESULTS Compared with the blank group and grain-moxibustion group， the HR， LVSP， +dp/dt_max and -dp/dt_max of the model group were reduced， while LVDP and t-dp/dt_max were increased（P<0.05）. Compared with the blank group， the activity of LDH， CK and the content of cTnI of the model group and the grain-moxibustion group were increased(P<0.05)， the content of H₂S in myocardium was reduced (P<0.05). Compared with the model group， the activity of LDH， CK and the content of cTnI of the grain-moxibustion group were reduced(P<0.05)， the content of H₂S in myocardium was increased (P<0.05). In the blank group， structure of myocardial cells is complete， intercellular space was normal without myocardial cells damage. While swelling， hyperemia and disordered arrangement of myocardial cells were observed by optical microscopy in the model group. But the situation of swelling and hyperemia in the grain-moxibustion group were milder than that in the model group. CONCLUSION Grain-moxibustion can improve the abnormal cardiac function and alleviate myocardial cells swelling and hyperemia which caused by ADR. The mechanism may be related with the regulation of the generation of endogenous H₂S.
- adriamycin /
- cardiotoxicity /
- grain-moxibustion /
- hydrogen sulfide

HTML全文

参考文献(14)

[1]	SHI Y， MOON M， DAWOOD S， et al. Mechanisms and management of doxorubicin cardiotoxicity[J]. Herz， 2011， 36(4):296-305.
[2]	CHATTERJEE K， ZHANG J， HONBO N， et al. Doxorubicin cardiomyopathy[J]. Cardiology， 2010， 115(2):155-162.
[3]	CALVERT JW， COETZEE WA， LEFER DJ．Novel insights into hydrogen sulfide-mediated cytoprotection[J]．Antioxid Redox Signal， 2010， 12(10):1203-1217.
[4]	LIU MH， LIN XL， YUAN C， et al. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells[J]. Mol Med Rep， 2016， 13(1):367-372.
[5]	XIE H， XU Q， JIA J，et al. Hydrogen sulfide protects against myocardial ischemia and reperfusion injury by activating AMP-activated protein kinase to restore autophagic flux[J]. Biochem Biophys Res Commun， 2015， 458(3):632-638.
[6]	LIU Y， LI Z， SHI X， et al. Neuroprotection of up-regulated carbon monoxide by electrical acupuncture on perinatal hypoxic-ischemic brain damage in rats[J]. Neurochem Res， 2014， 39(9):1724-1732.
[7]	刘洪智，高传玉，曹林生，等．阿霉素心肌病大鼠模型的建立与评价[J].武汉大学学报（医学版），2007，28(4)：500-503.
[8]	LIU HZ， GAO CY， CAO LS， et al. Establishment and evaluation of the adriamycin-induced dilated cardiomyopathy model in rats[J].Med J Wuhan Univ，2007，28(4)：500-503.
[9]	王欣君，王玲玲，张建斌．麦粒灸的灸量调控[J].上海针灸杂志，2013，32(6)：426-429．
[10]	WANG XJ， WANG LL， ZHANG JB. Quantity regulation in grain moxibustion[J].Shanghai J Acu mox，2013，32(6)：426-429．
[11]	LAGOA R， GANAN C， LOPEZ-SANCHEZ C， et al. The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity[J]. Biomarkers， 2014， 19(2):142-153.
[12]	GUO R， WU K， CHEN J， et al. Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK/NFκB pathway in H9c2 cardiac cells[J]. Cell Physiol Biochem， 2013， 32(6):1668-1680.
[13]	张海兵.艾灸治疗肿瘤放、化疗副作用举隅[J]. 湖南中医杂志，2010，26(6):82-83.
[14]	ZHANG HB. Side effects of moxibustion therapy for tumor radiotherapy and chemotherapy[J]. Hunan J Tradit Chin Med，2010，26(6):82-83.