抗支糖浆心脏毒性的安全性评价

Safety Evaluation of Kangzhi Syrup in Cardiac Toxicity

目的:通过抗支糖浆心脏毒性的安全性评价方法,验证制剂正常剂量下服用的安全性。方法:将40只SD大鼠随机分为4组:空白对照组、抗支糖浆低(4.40 g·kg^(-1))、中(17.60 g·kg^(-1))、高(35.20 g·kg^(-1))剂量组,每组10只。除空白对照组外,其余各组灌胃给药,2次/d,连续7 d。记录动物反应和体质量,进行心电图检测,测定心肌酶谱羟丁酸脱氢酶(HBDH)、肌酸激酶同功酶(CK-MB)、乳酸脱氢酶(LDH)、肌酸激酶(CK)的含量,测定心脏脏器系数,进行组织形态学检查。结果:空白对照组和抗支糖浆低、中剂量组大鼠外表及行为正常,体质量增长稳定;高剂量组大鼠给药后活动减少,食量减退,毛色暗淡且杂乱,大便黏稠。心电图变化结果显示,ST段的改变无显著性变化,给药第4天,中、高剂量组T波幅度发生显著性变化,高剂量组出现宽大的QRS波,出现心律失常,心率升高(P<0.05),但给药第7天均无显著性差异。与空白对照组比较,抗支糖浆中剂量组CK-MB、LDH活性明显上升,高剂量组LDH、HBDH、CK、CK-MB活性明显上升(P<0.05),心脏脏器系数无明显差异(P>0.05)。空白对照组和抗支糖浆低、中剂量组大鼠的心肌纤维排列规整,间隙规律,染色均匀,细胞质胞核清晰,但高剂量组大鼠的心肌纤维排列不规整,局部出现断裂,心肌细胞染色不均匀,心肌细胞间有炎细胞浸润。结论:正常剂量服用抗支糖浆对大鼠心脏无明显毒性,用药安全。

Objective: To validate the safety of Kangzhi syrup at normal dosage by evaluating the safety of Kangzhi syrup in cardiotoxicity. Methods: Totally 40 SD rats were randomly divided into 4 groups: the blank control group,and Kangzhi syrup low( 4. 40 g·kg^-1),medium( 17. 60 g·kg^-1),high( 35. 20 g·kg^-1) dosage groups with 10 ones in each. Except for the blank control group,the other groups were with intragastric administration,twice per day for 7 days. The animal response and body mass were recorded,the electrocardiogram was tested,the contents of myocardial enzymogram hydroxybutyrate dehydrogenase( HBDH),creatine kinase isoenzyme( CK-MB),lactate dehydrogenase( LDH) and creatine kinase( CK) were determined,the heart organ coefficient was determined,and the histopathological examination was performed. Results: The appearance and behavior of rats in the blank control group and Kangzhi syrup low and medium dose groups were normal,and their body weight increased steadily. In the high dose group,the activity decreased,the food intake decreased,the hair color was dim and disorderly,and the stool was thick. The results of electrocardiogram showed that there was no significant change in ST segment. On the 4 th day of administration,the T wave amplitude of the midium and high dose groups changed significantly,and the QRS wave,arrhythmia and heart rate increased in the high dose group( P< 0. 05),while there was no significant difference on the 7 th day of administration. Compared with those in the blank control group,CK-MB and LDH activities in the medium dose group of Kangzhi syrup increased significantly,LDH,HBDH,CK and CK-MB activities in the high dose group increased significantly( P < 0. 05),and there was no significant difference in cardiac organ coefficient( P >0. 05). The myocardial fibers of rats in the blank control group and Kangzhi syrup low and medium dose groups were arranged regularly with regular interstitial space,uniform staining and clear cytoplasmic nucleus. However,the myocardial fibers of rats in the high dose group were arranged irregularly with local rupture,uneven staining of myocardial cells and infiltration of inflammatory cells among myocardial cells. Conclusion: The results of the experiment verify that the normal dose of Kangzhi syrup has no obvious toxicity to the rat heart,and the medication is safe.