芪附汤及其拆方干预阿霉素心脏毒性的药效学与作用机制研究
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摘要
目的:
通过考察芪附汤及其拆方对阿霉素心脏毒性模型大鼠的一般状态、体质量与心脏质量及其心脏指数、心电图、心肌组织形态的变化,了解芪附汤及其拆方干预阿霉素心脏毒性的效应;通过检测心肌SOD与GSH-Px活性与含量、MDA含量以及心肌细胞凋亡率和Bax、Bcl-2、P53、Caspaes-3的mRNA表达水平的变化,探讨芪附汤及其拆方干预阿霉素心脏毒性的抗氧化应激和抑制细胞凋亡的作用机制。
材料与方法:
本实验采用阿霉素(2mg/kg,每周1次)腹腔注射的方法复制阿霉素心脏毒性损伤大鼠模型,同时予以芪附汤及其拆方进行干预。除正常组、模型组外,正常大鼠给予附子水煎液灌胃为附子1组,中药对照组以生脉饮作为中药阳性对照药灌胃给药,以芪附汤及其拆方——黄芪组、附子2组、芪附汤组作为药物治疗组。造模与给药均共4周,同时观察大鼠的一般状态。4周后检测心电图;处死动物并摘取心脏进行指标检测。称取心脏质量,计算心脏指数(心脏质量/体质量),留取一部分心肌标本,通过光镜与电镜观察心肌组织形态变化及心肌细胞超微结构改变,采用化学比色法检测SOD、GSH-Px活性和MDA含量,采用ELISA法检测SOD和GSH-Px的含量,以流式细胞术检测心肌细胞凋亡率,实时定量PCR检测Bax与Bcl-2的mRNA表达水平,并计算其比值,实时定量PCR检测P53、Caspaes-3的mRNA表达水平。
结果:
1.大鼠一般状态:与正常组相比,模型组大鼠出现不同程度的精神萎靡,活动减少,喜蜷卧,抓取时反抗力减弱;毛发干枯、无光泽,伴有脱毛现象,有些大鼠口鼻可见明显血渍,腹水,个别出现腹泻等症状;与模型组大鼠相比,中药对照组、黄芪组、芪附汤组大鼠上述症状均较轻,其中黄芪组大鼠一般状态相对最好。附子2组大鼠一般状态不及模型组。附子1组大鼠一般状态与正常组基本一致。
2.大鼠体质量,心脏质量和心脏指数:与正常组比较,模型组大鼠体质量显著下降,有统计学意义(P﹤0.05);与模型组相比,中药对照组、黄芪组、芪附汤组大鼠体质量显著增长,有统计学意义(P﹤0.05)。与正常组比较,模型组心脏质量下降,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组心脏质量均有不同程度增长(P﹥0.05)。与正常组比较,其他各组心脏指数均有所下降(P﹥0.05);与模型组相比,各给药组心脏指数无明显变化(P﹥0.05)。附子1组大鼠体质量、心脏质量和心脏指数与正常组基本一致。
3.大鼠心电图变化:与正常组相比,模型组大鼠心率显著减慢(P﹤0.05),QRS波群电压和明显降低(P﹤0.05),与用药前心电图相比减低30%以上,Q-T间期明显延长(P﹤0.05),个别出现心律失常;与模型组相比,芪附汤组、黄芪组、中药对照组和附子2组大鼠心率增加显著,芪附汤组、黄芪组和附子2组大鼠QRS波群电压和明显增高,芪附汤组、黄芪组和中药对照组大鼠Q-T间期显著缩短,均有统计学意义(P﹤0.05)。附子1组大鼠心率、QRS波群电压和与Q-T间期和正常组基本一致。
4.光镜下和电镜下心肌组织形态学变化:光镜下观察模型组大鼠心肌细胞呈颗粒变性,肌间隙增宽,部分心肌纤维断裂,少数淋巴细胞侵润;电镜下观察模型组大鼠心肌细胞超微结构明显损伤,肌丝断裂溶解,Z线排列宽窄不一、部分溶解,线粒体肿胀,部分嵴断裂模糊不清,个别形成大小不等空泡。附子2组大鼠心肌病理改变较模型组更为严重,中药对照组、黄芪组与芪附汤组大鼠心肌组织形态有不同程度改善。附子1组大鼠心肌有轻微病理改变,接近正常心肌组织。
5.大鼠心肌细胞SOD活性和含量的变化:与正常组比较,模型组大鼠心肌细胞SOD活性减弱,含量降低,有统计学意义(P﹤0.05)。与模型组比较,中药对照组、黄芪组、芪附汤组大鼠心肌细胞SOD活性升高,均有统计学意义(P﹤0.05)。
6.大鼠心肌细胞GSH-Px活性和含量的变化:与正常组比较,模型组大鼠心肌细胞GSH-Px活性降低,含量减少,有统计学意义(P﹤0.05);与模型组比较,中药对照组、黄芪组、芪附汤组大鼠心肌细胞GSH-Px活性升高,各用药组大鼠心肌细胞GSH-Px含量升高,均有统计学意义(P﹤0.05)。
7.大鼠心肌细胞MDA含量测检的变化:与正常组比较,模型组大鼠心肌细胞MDA含量升高,有统计学意义(P﹤0.05);与模型组比较,中药对照组,黄芪组,芪附汤组大鼠心肌细胞MDA含量降低,有统计学意义(P﹤0.05)。
8.心肌细胞凋亡率显示:与正常组比较,模型组大鼠心肌细胞凋亡率显著上升,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组大鼠心肌细胞凋亡率均有显著下降,有统计学意义(P﹤0.05)。
9.大鼠心肌Bax与Bcl-2的mRNA表达结果:与正常组比较,模型组大鼠心肌Bax的mRNA表达水平上调,Bcl-2的mRNA表达水平下调,Bcl-2/Bax降低,均有统计学意义(P﹤0.05)。与模型组比较,附子2组、黄芪组、芪附汤组大鼠心肌Bax的mRNA表达水平下调;中药对照组,黄芪组,芪附汤组大鼠心肌Bcl-2的mRNA表达水平上调,有统计学意义(P﹤0.05);中药对照组、黄芪组、芪附汤组Bcl-2/Bax升高,有统计学意义(P﹤0.05)。
10.大鼠心肌P53的mRNA表达结果:与正常组比较,模型组P53的mRNA表达水平上调,有统计学意义(P﹤0.05);与模型组比较,中药对照组、黄芪组、芪附汤组P53的mRNA表达水平下调,有统计学意义(P﹤0.05)。
11.大鼠心肌Caspase-3的mRNA表达显示:与正常组比较,模型组Caspase-3的mRNA表达水平上调,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组Caspase-3的mRNA表达水平下调,均有统计学意义(P﹤0.05)。
结论:
在本实验条件下,
1.附子与阿霉素合用具有心脏毒性叠加作用。
2.芪附汤和黄芪对阿霉素心脏毒性具有防护作用。
3.芪附汤和黄芪防护阿霉素心脏毒性损伤的机制与抗氧化应激、抑制凋亡相关。
Purpose:To observe the general conditions, the survival rate, body weight, heart weight and radio of heart/body weight, electrocardiogram changes, myocardial histomorphological changes in the rats with adriamycin-induceded cardiotoxicity, Qi-fu Decoction was given simultaneously, the effect of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity has been demonstrated. To measure the activity and content of superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px), the content of malondialdehyde (MDA), cardiomyocyte apoptosis rate, the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3, which might be related with antioxidant stress and the inhibiting apoptosis of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity.
Material and method:The method of injecting adriamycin(ADR) intraperitoneally was adopted to duplicat the rat model of ADR-induced cardiotoxicity. Qi-fu Decoction and its decomposed recipes were given simultaneously.besides the the normal group and the model group, fuzi water solution was given intragastrically to the rats of fuzi 1 group without duplicating ADR-induced cardiotoxicity model. Shengmai Yin was given intragastrically to the rats of Chinese herb control group, Qi-fu Decoction and its decomposed recipes--- fuzi group, Huangqi group and Qifu decoction group were taken as drug treatment groups. There were 4 weeks in administrating ADR and giving medicine, in the same tiame, the general conditions of the rats were observed. After 4 weeks, the rats were sacrificed and their hearts were removed.the indexes about the heart were measured. heart weight, radio of heart/body weight, myocardial histomorphological changes observd by light and light and electron microscopy, the activity SOD, GSH-Px and the content of MDA measured by chemical colorimetric assay, and the content of SOD,GSH-Px and MDA by Enzyme-linked immunosorbent assay,the cardiomyocyte apoptosis rate by flow cytometry., the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3 by real time polymerase chain reaction.
Results:
1. The general condition: compared with the general condition of the normal group, that of the model group were manifested by listlessness, activity decreased, curl up lie, grabbed resistance weakened, hair without luster, accompanied depilate, blood in the mouth and nose of some rats can be obviously observed, individual occurrence of ascites, diarrhea. Compared with that of the model group, the symptoms of Chinese herb control, huangqi group, Qifu decoction group were better, that of fuzi group were worse. The general conditions of fuzi 1 group were similar to that of the normal group.
2.The body weight, the heart weight and the heart index of the rats: the body weight of the rats fell much than that of the model group, with statistical significance (P﹤0.01). Compared with the body weight of the rats in the model group, that of control Chinese medicin group, huangqi group, Qifu decoction group were increased, with statistical significance (P﹤0.05),that of huangqi group is the most. the heart weight of the rats fell much than that of the model group, with statistical significance (P﹤0.05). Compared with the heart weight of the rats in the model group, that of control Chinese medicin group,fuzi group, huangqi group, Qifu decoction group were increased in a degree(P﹥0.05).the heart index of the model group is decreased slightly compared with that of the normal group (P﹥0.05), compared with that of the model group, there were no obvious changes in the heart index of the other groups(P﹥0.05). The body weight, the heart weight and the heart index of the rats in fuzi 1 group were similar to that of the normal group.
3. Electrocardiogram: compared with that of the normal group, the heart rate group was slower(P﹤0.01), QRS volvage sum decreaced(P﹤0.05), Q-T interphase extended(P﹤0.05)of the model group, individual appeard arrhythmia. Compared with that of the model group, the heart rate was more quicker of all administrated groups, QRS volvage sum increased of huangqi group, qifu decoction group and fuzi2 group, Q-T interphase shorten of , huangqi group, qifu decoction group and chinese herb control,all with statistical significance(P﹤0.05). The heart rate, QRS volvage sum and Q-T interphase of the rats in fuzi 1 group were similar to that of the normal group.
4.Cardiac histomorphologic chang observed by light microscope and electron microscope: Observed by light microscope, there were flocular degeneration in cardiac myocytes, myocardial gap widened, part of myocardial fiber fractured, and a few lymphocytes penetration embellished in the rats’cardiomyocytes of the model group. Observed by electron microscope, there were myocardial filaments fractured and dissolved, Z line arrangement in disorder, part of Z line dissolved, mitochondrial swelling and its crista ruptured, vacuole foumed in the cardiac myocyte of the model group. The pathological changes of the rats’cardiomyocytes of fuzi group were worse than that of the model group, Cardiac histomorphologes were improved in different degree of Chinese herb controlgroup, huangqi group and qifu decoction group. There were slight pathological chang in the rats’cardiomyocytes of fuzi 1 group.
5. The activity and content of SOD of the rat’s cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of SOD of the model group, with statistical significance (P﹤0.05). Compared with that of the model group, SOD activity is enhanced of Chinese herb controlgroup, huangqi group and qifu decoction group, with statistical significance (P﹤0.05), qifu decoction group is the most, that of fuzi group is weakened (P﹥0.05). SOD content is increased of chinese herb control and huangqi group, with statistical significance (P﹤0.05).
6. The activity and content of GSH-Px of the rat’s cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of GSH-Px of the model group, with statistical significance (P﹤0.05). Compared with that of the model group, GSH-Px activity is enhanced of chinese herb control, huangqi group and qifu decoction group, GSH-Px content is increased of all administrated group, all with statistical significance (P﹤0.05).
7. MDA content of the rat’s cardiac myocyte: Compared with that of the normal group, MDA content of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, MDA content of chinese herb control, huangqi group and qifu decoction group is decreased, with statistical significance (P﹤0.05).
8. Apoptosis rate of cardiac myocyte: Compared with that of the normal group, apoptosis rate of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, apoptosis rate is increased of chinese herb control, fizi group, huangqi group and qifu decoction group,all with statistical significance (P﹤0.05).
9. Bax mRNA and Bcl-2mRNA expression and Bcl-2/Bax of the myocardium of the rats: Compared with that of the normal group, BaxmRNA expression is increased, Bcl-2 mRNA expression is decreased, Bcl-2/ Bax decreased, of the model group, all with statistical significance (P﹤0.05). Compared with that of the model group, Bax mRNA expression is decreased of fizi group, huangqi group and qifu decoction group, Bcl-2 mRNA expression and Bcl-2/ Bax are increased of chinese herb control, huagnqi group and qifu decoction group, all with statistical significance (P﹤0.05).
10. P53 mRNA expression of the myocardium of the rats: Compared with that of the normal group, P53mRNA expression of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, P53mRNA expression is decreased, of all administrated group, all with statistical significance (P﹤0.05).
11. caspase-3mRNA expression of the myocardium of the rats: compared with that of the normal group, caspase-3 mRNA expression of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, caspase-3 mRNA expression is decreased, of all administrated group, all with statistical significance (P﹤0.05) and the huangqi group is the most.
Conclusion:
1.Fuzi can increase adriamycin-induced cardiotoxicity。
2.Qifu decoction and Huangqi can protect the rats from adriamycin-induced cardiotoxicity。
3.The mechanisms is related to antioxidant stress and inhibiting apoptosis.
通过考察芪附汤及其拆方对阿霉素心脏毒性模型大鼠的一般状态、体质量与心脏质量及其心脏指数、心电图、心肌组织形态的变化,了解芪附汤及其拆方干预阿霉素心脏毒性的效应;通过检测心肌SOD与GSH-Px活性与含量、MDA含量以及心肌细胞凋亡率和Bax、Bcl-2、P53、Caspaes-3的mRNA表达水平的变化,探讨芪附汤及其拆方干预阿霉素心脏毒性的抗氧化应激和抑制细胞凋亡的作用机制。
材料与方法:
本实验采用阿霉素(2mg/kg,每周1次)腹腔注射的方法复制阿霉素心脏毒性损伤大鼠模型,同时予以芪附汤及其拆方进行干预。除正常组、模型组外,正常大鼠给予附子水煎液灌胃为附子1组,中药对照组以生脉饮作为中药阳性对照药灌胃给药,以芪附汤及其拆方——黄芪组、附子2组、芪附汤组作为药物治疗组。造模与给药均共4周,同时观察大鼠的一般状态。4周后检测心电图;处死动物并摘取心脏进行指标检测。称取心脏质量,计算心脏指数(心脏质量/体质量),留取一部分心肌标本,通过光镜与电镜观察心肌组织形态变化及心肌细胞超微结构改变,采用化学比色法检测SOD、GSH-Px活性和MDA含量,采用ELISA法检测SOD和GSH-Px的含量,以流式细胞术检测心肌细胞凋亡率,实时定量PCR检测Bax与Bcl-2的mRNA表达水平,并计算其比值,实时定量PCR检测P53、Caspaes-3的mRNA表达水平。
结果:
1.大鼠一般状态:与正常组相比,模型组大鼠出现不同程度的精神萎靡,活动减少,喜蜷卧,抓取时反抗力减弱;毛发干枯、无光泽,伴有脱毛现象,有些大鼠口鼻可见明显血渍,腹水,个别出现腹泻等症状;与模型组大鼠相比,中药对照组、黄芪组、芪附汤组大鼠上述症状均较轻,其中黄芪组大鼠一般状态相对最好。附子2组大鼠一般状态不及模型组。附子1组大鼠一般状态与正常组基本一致。
2.大鼠体质量,心脏质量和心脏指数:与正常组比较,模型组大鼠体质量显著下降,有统计学意义(P﹤0.05);与模型组相比,中药对照组、黄芪组、芪附汤组大鼠体质量显著增长,有统计学意义(P﹤0.05)。与正常组比较,模型组心脏质量下降,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组心脏质量均有不同程度增长(P﹥0.05)。与正常组比较,其他各组心脏指数均有所下降(P﹥0.05);与模型组相比,各给药组心脏指数无明显变化(P﹥0.05)。附子1组大鼠体质量、心脏质量和心脏指数与正常组基本一致。
3.大鼠心电图变化:与正常组相比,模型组大鼠心率显著减慢(P﹤0.05),QRS波群电压和明显降低(P﹤0.05),与用药前心电图相比减低30%以上,Q-T间期明显延长(P﹤0.05),个别出现心律失常;与模型组相比,芪附汤组、黄芪组、中药对照组和附子2组大鼠心率增加显著,芪附汤组、黄芪组和附子2组大鼠QRS波群电压和明显增高,芪附汤组、黄芪组和中药对照组大鼠Q-T间期显著缩短,均有统计学意义(P﹤0.05)。附子1组大鼠心率、QRS波群电压和与Q-T间期和正常组基本一致。
4.光镜下和电镜下心肌组织形态学变化:光镜下观察模型组大鼠心肌细胞呈颗粒变性,肌间隙增宽,部分心肌纤维断裂,少数淋巴细胞侵润;电镜下观察模型组大鼠心肌细胞超微结构明显损伤,肌丝断裂溶解,Z线排列宽窄不一、部分溶解,线粒体肿胀,部分嵴断裂模糊不清,个别形成大小不等空泡。附子2组大鼠心肌病理改变较模型组更为严重,中药对照组、黄芪组与芪附汤组大鼠心肌组织形态有不同程度改善。附子1组大鼠心肌有轻微病理改变,接近正常心肌组织。
5.大鼠心肌细胞SOD活性和含量的变化:与正常组比较,模型组大鼠心肌细胞SOD活性减弱,含量降低,有统计学意义(P﹤0.05)。与模型组比较,中药对照组、黄芪组、芪附汤组大鼠心肌细胞SOD活性升高,均有统计学意义(P﹤0.05)。
6.大鼠心肌细胞GSH-Px活性和含量的变化:与正常组比较,模型组大鼠心肌细胞GSH-Px活性降低,含量减少,有统计学意义(P﹤0.05);与模型组比较,中药对照组、黄芪组、芪附汤组大鼠心肌细胞GSH-Px活性升高,各用药组大鼠心肌细胞GSH-Px含量升高,均有统计学意义(P﹤0.05)。
7.大鼠心肌细胞MDA含量测检的变化:与正常组比较,模型组大鼠心肌细胞MDA含量升高,有统计学意义(P﹤0.05);与模型组比较,中药对照组,黄芪组,芪附汤组大鼠心肌细胞MDA含量降低,有统计学意义(P﹤0.05)。
8.心肌细胞凋亡率显示:与正常组比较,模型组大鼠心肌细胞凋亡率显著上升,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组大鼠心肌细胞凋亡率均有显著下降,有统计学意义(P﹤0.05)。
9.大鼠心肌Bax与Bcl-2的mRNA表达结果:与正常组比较,模型组大鼠心肌Bax的mRNA表达水平上调,Bcl-2的mRNA表达水平下调,Bcl-2/Bax降低,均有统计学意义(P﹤0.05)。与模型组比较,附子2组、黄芪组、芪附汤组大鼠心肌Bax的mRNA表达水平下调;中药对照组,黄芪组,芪附汤组大鼠心肌Bcl-2的mRNA表达水平上调,有统计学意义(P﹤0.05);中药对照组、黄芪组、芪附汤组Bcl-2/Bax升高,有统计学意义(P﹤0.05)。
10.大鼠心肌P53的mRNA表达结果:与正常组比较,模型组P53的mRNA表达水平上调,有统计学意义(P﹤0.05);与模型组比较,中药对照组、黄芪组、芪附汤组P53的mRNA表达水平下调,有统计学意义(P﹤0.05)。
11.大鼠心肌Caspase-3的mRNA表达显示:与正常组比较,模型组Caspase-3的mRNA表达水平上调,有统计学意义(P﹤0.05);与模型组比较,中药对照组、附子2组、黄芪组、芪附汤组Caspase-3的mRNA表达水平下调,均有统计学意义(P﹤0.05)。
结论:
在本实验条件下,
1.附子与阿霉素合用具有心脏毒性叠加作用。
2.芪附汤和黄芪对阿霉素心脏毒性具有防护作用。
3.芪附汤和黄芪防护阿霉素心脏毒性损伤的机制与抗氧化应激、抑制凋亡相关。
Purpose:To observe the general conditions, the survival rate, body weight, heart weight and radio of heart/body weight, electrocardiogram changes, myocardial histomorphological changes in the rats with adriamycin-induceded cardiotoxicity, Qi-fu Decoction was given simultaneously, the effect of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity has been demonstrated. To measure the activity and content of superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px), the content of malondialdehyde (MDA), cardiomyocyte apoptosis rate, the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3, which might be related with antioxidant stress and the inhibiting apoptosis of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity.
Material and method:The method of injecting adriamycin(ADR) intraperitoneally was adopted to duplicat the rat model of ADR-induced cardiotoxicity. Qi-fu Decoction and its decomposed recipes were given simultaneously.besides the the normal group and the model group, fuzi water solution was given intragastrically to the rats of fuzi 1 group without duplicating ADR-induced cardiotoxicity model. Shengmai Yin was given intragastrically to the rats of Chinese herb control group, Qi-fu Decoction and its decomposed recipes--- fuzi group, Huangqi group and Qifu decoction group were taken as drug treatment groups. There were 4 weeks in administrating ADR and giving medicine, in the same tiame, the general conditions of the rats were observed. After 4 weeks, the rats were sacrificed and their hearts were removed.the indexes about the heart were measured. heart weight, radio of heart/body weight, myocardial histomorphological changes observd by light and light and electron microscopy, the activity SOD, GSH-Px and the content of MDA measured by chemical colorimetric assay, and the content of SOD,GSH-Px and MDA by Enzyme-linked immunosorbent assay,the cardiomyocyte apoptosis rate by flow cytometry., the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3 by real time polymerase chain reaction.
Results:
1. The general condition: compared with the general condition of the normal group, that of the model group were manifested by listlessness, activity decreased, curl up lie, grabbed resistance weakened, hair without luster, accompanied depilate, blood in the mouth and nose of some rats can be obviously observed, individual occurrence of ascites, diarrhea. Compared with that of the model group, the symptoms of Chinese herb control, huangqi group, Qifu decoction group were better, that of fuzi group were worse. The general conditions of fuzi 1 group were similar to that of the normal group.
2.The body weight, the heart weight and the heart index of the rats: the body weight of the rats fell much than that of the model group, with statistical significance (P﹤0.01). Compared with the body weight of the rats in the model group, that of control Chinese medicin group, huangqi group, Qifu decoction group were increased, with statistical significance (P﹤0.05),that of huangqi group is the most. the heart weight of the rats fell much than that of the model group, with statistical significance (P﹤0.05). Compared with the heart weight of the rats in the model group, that of control Chinese medicin group,fuzi group, huangqi group, Qifu decoction group were increased in a degree(P﹥0.05).the heart index of the model group is decreased slightly compared with that of the normal group (P﹥0.05), compared with that of the model group, there were no obvious changes in the heart index of the other groups(P﹥0.05). The body weight, the heart weight and the heart index of the rats in fuzi 1 group were similar to that of the normal group.
3. Electrocardiogram: compared with that of the normal group, the heart rate group was slower(P﹤0.01), QRS volvage sum decreaced(P﹤0.05), Q-T interphase extended(P﹤0.05)of the model group, individual appeard arrhythmia. Compared with that of the model group, the heart rate was more quicker of all administrated groups, QRS volvage sum increased of huangqi group, qifu decoction group and fuzi2 group, Q-T interphase shorten of , huangqi group, qifu decoction group and chinese herb control,all with statistical significance(P﹤0.05). The heart rate, QRS volvage sum and Q-T interphase of the rats in fuzi 1 group were similar to that of the normal group.
4.Cardiac histomorphologic chang observed by light microscope and electron microscope: Observed by light microscope, there were flocular degeneration in cardiac myocytes, myocardial gap widened, part of myocardial fiber fractured, and a few lymphocytes penetration embellished in the rats’cardiomyocytes of the model group. Observed by electron microscope, there were myocardial filaments fractured and dissolved, Z line arrangement in disorder, part of Z line dissolved, mitochondrial swelling and its crista ruptured, vacuole foumed in the cardiac myocyte of the model group. The pathological changes of the rats’cardiomyocytes of fuzi group were worse than that of the model group, Cardiac histomorphologes were improved in different degree of Chinese herb controlgroup, huangqi group and qifu decoction group. There were slight pathological chang in the rats’cardiomyocytes of fuzi 1 group.
5. The activity and content of SOD of the rat’s cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of SOD of the model group, with statistical significance (P﹤0.05). Compared with that of the model group, SOD activity is enhanced of Chinese herb controlgroup, huangqi group and qifu decoction group, with statistical significance (P﹤0.05), qifu decoction group is the most, that of fuzi group is weakened (P﹥0.05). SOD content is increased of chinese herb control and huangqi group, with statistical significance (P﹤0.05).
6. The activity and content of GSH-Px of the rat’s cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of GSH-Px of the model group, with statistical significance (P﹤0.05). Compared with that of the model group, GSH-Px activity is enhanced of chinese herb control, huangqi group and qifu decoction group, GSH-Px content is increased of all administrated group, all with statistical significance (P﹤0.05).
7. MDA content of the rat’s cardiac myocyte: Compared with that of the normal group, MDA content of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, MDA content of chinese herb control, huangqi group and qifu decoction group is decreased, with statistical significance (P﹤0.05).
8. Apoptosis rate of cardiac myocyte: Compared with that of the normal group, apoptosis rate of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, apoptosis rate is increased of chinese herb control, fizi group, huangqi group and qifu decoction group,all with statistical significance (P﹤0.05).
9. Bax mRNA and Bcl-2mRNA expression and Bcl-2/Bax of the myocardium of the rats: Compared with that of the normal group, BaxmRNA expression is increased, Bcl-2 mRNA expression is decreased, Bcl-2/ Bax decreased, of the model group, all with statistical significance (P﹤0.05). Compared with that of the model group, Bax mRNA expression is decreased of fizi group, huangqi group and qifu decoction group, Bcl-2 mRNA expression and Bcl-2/ Bax are increased of chinese herb control, huagnqi group and qifu decoction group, all with statistical significance (P﹤0.05).
10. P53 mRNA expression of the myocardium of the rats: Compared with that of the normal group, P53mRNA expression of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, P53mRNA expression is decreased, of all administrated group, all with statistical significance (P﹤0.05).
11. caspase-3mRNA expression of the myocardium of the rats: compared with that of the normal group, caspase-3 mRNA expression of the model group is increased, with statistical significance (P﹤0.05). Compared with that of the model group, caspase-3 mRNA expression is decreased, of all administrated group, all with statistical significance (P﹤0.05) and the huangqi group is the most.
Conclusion:
1.Fuzi can increase adriamycin-induced cardiotoxicity。
2.Qifu decoction and Huangqi can protect the rats from adriamycin-induced cardiotoxicity。
3.The mechanisms is related to antioxidant stress and inhibiting apoptosis.
引文
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