藜芦与人参配伍连续8周给药对大鼠心脏毒性的影响

Effects of the combination of Veratrum nigrum L. and Panax ginseng on cardiac toxicity: An 8-week oral administration study in rats

目的:比较藜芦与人参配伍及藜芦单用对大鼠心脏毒性的差异。方法:SD大鼠分为空白对照组,藜芦单药组,人参配伍藜芦的低、中、高剂量组;每日灌胃给药1次,连续8周后取大鼠血清,测定血清天门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)及α-羟丁酸脱氢酶(α-HBDH)活性,同时取各组大鼠心脏进行组织病理学检查。结果:配伍低、中剂量组心肌酶学指标与藜芦单药组比较具有显著性差异(P<0.05,P<0.01);各组间心脏重量、心脏系数无统计学差异;配伍后大鼠心脏组织出现明显损伤,可导致心肌散在性坏死和炎细胞浸润灶,量效关系明显。结论:病理观察结合生化酶活性测定结果显示,配伍合用时,低、中、高3个剂量对大鼠心脏毒性影响程度均明显高于藜芦单药,显示藜芦人参配伍合用可明显增强藜芦的心脏毒性,提示临床两药合用应谨慎。

Objective： To compare the cardiac toxicity of the aqueous extract of Veratrum nigrum L. （VN） with that of Radix Ginseng-VN. combination （GVN） in rats. Methods： SD rats were divided into blank control group, single VN group, and low, medium, high dose of GVN groups. Drugs or 0.9% sodium chloride solution were administered to them once a day. After 8 weeks, serum was collected to analyze the activity of aspartate aminotransferase （AST）, creatine kinase （CK）, MB isoenzyme of creatine kinase （CK-MB）, lactic dehydrogenase （LDH） and alpha-hydroxybutyrate dehydrogenase （alpha-HBDH）. At the same time, heart tissues of each group were taken for histopathological analyses. Results： Significant differences between low GVN group/medium GVN group and single VN group were observed in enzymology indexes （P〈0.05, P〈0.01）. There was no statistical difference among all groups in heart weight and heart coefficient. After compatibility, histopathological changes such as scattered myocardial necrosis and infiltration foci of inflammatory cells in cardiac tissues were observed, with an obvious concentration- response relationship. Conclusion： The cardiac toxicity of high, medium and low doses of GVN was significantly higher than that of single VN, which indicated that combination of GVN could considerably enhance the cardiac toxicity of VN according to the evidences of histopathological examination and zymologic tests.