麦粒灸对阿霉素心肌病大鼠硫化氢信号分子的影响

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

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2d,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/dtmax)、左室内压最大下降速率(-dp/dtmax)、左室内压变化时间(t-dp/dtmax);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/dtmax、-dp/dtmax降低(P<0.05),LVDP和t-dp/dtmax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。

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 30SPF-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),5cones at each acupoint,once daily for 4weeks,2dof rest per week.At the end of the last intervention,we detected HR,LVSP),LVDP,+dp/dtmax,-dp/dtmaxand t-dp/dtmax.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 H2 S,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.RESULTSCompared with the blank group and grain-moxibustion group,the HR,LVSP,+dp/dtmaxand-dp/dtmaxof the model group were reduced,while LVDP and t-dp/dtmaxwere 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 H2 S 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 H2 S 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 H2 S.