灵芝多糖对阿霉素所致心肌损伤的作用及机制研究

Effect and mechanism of Ganoderma lucidum polysaccharide on myocardial injury induced by doxorubicin

摘要:

目的 探讨灵芝多糖对阿霉素（多柔比星）所致心肌损伤的作用及可能的机制。方法 腹腔注射阿霉素复制大鼠急性心肌损伤模型，观察低、高剂量灵芝多糖对大鼠血清心肌酶指标、心肌组织及抗氧化酶活力的影响；低、高剂量灵芝多糖预处理大鼠H₉C₂心肌细胞，再与阿霉素共培养，通过CCK-8法检测细胞活力，ELISA法检测H₉C₂大鼠心肌细胞和大鼠心肌组织中的肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-６）及白细胞介素-10（IL-10）水平。结果 灵芝多糖高剂量+阿霉素组和灵芝多糖低剂量+阿霉素组大鼠一般情况明显优于阿霉素组；阿霉素组大鼠心肌酶水平升高、心肌组织结构受损；灵芝多糖高剂量+阿霉素组和灵芝多糖低剂量+阿霉素组较阿霉素组心肌酶水平降低、心肌组织结构受损程度减轻（P <0.05）；阿霉素组H₉C₂心肌细胞存活率降低，灵芝多糖高剂量+阿霉素组和灵芝多糖低剂量+阿霉素组较阿霉素组升高（P <0.05）；灵芝多糖高剂量+阿霉素组和灵芝多糖低剂量+阿霉素组大鼠心肌组织及H₉C₂细胞与阿霉素组比较，抗氧化酶活力升高，促炎症因子减少，抗炎症因子增加（P <0.05）。结论 灵芝多糖在体内和体外均有减轻阿霉素所致心脏毒性的作用。

Abstract:

Objective To study the protective effect and possible mechanism of Ganoderma lucidum polysaccharide on myocardial injury caused by doxorubicin.Methods The rat model of acute myocardial injury was established by intraperitoneal injection of doxorubicin, and we observed the effects of low and high doses of Ganoderma lucidum polysaccharide intervention on myocardial enzyme spectrum, myocardial histopathology and antioxidase activity. For H₉C₂ cells treated with low or high doses of Ganoderma lucidum polysaccharide in advance and then cocultured with doxorubicin, we detected the cell viability via cell counting kit-8 (CCK-8). Besides, the concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10 in H₉C₂ cells and myocardial tissues of rats were determined by enzyme-linked immunoabsorbent assay (ELISA).Results The general condition of the rats in high-dose Ganoderma lucidum polysaccharide + doxorubicin group and low-dose Ganoderma lucidum polysaccharide + doxorubicin group was better than that of the rats in doxorubicin group (P < 0.05). The extents of the decline of antioxidase activity and the damage of myocardial tissues were reduced in high-dose Ganoderma lucidum polysaccharide + doxorubicin group and low-dose Ganoderma lucidum polysaccharide + doxorubicin group (P < 0.05). The survival rate of H9C2 cells was lower in doxorubicin group than that of the other two groups (P < 0.05). Besides, the antioxidase activity was increased, pro-inflammatory factors were downregulated, and anti-inflammatory factors were upregulated in H9C2 cells and myocardial tissues of the rats in high-dose Ganoderma lucidum polysaccharide + doxorubicin group and low-dose Ganoderma lucidum polysaccharide + doxorubicin group in comparison to doxorubicin group (P < 0.05).Conclusion Ganoderma lucidum polysaccharide plays roles in ameliorating the cardiotoxicity of doxorubicin both in vivo and in vitro.