当归多糖对顺铂化疗H22腹水瘤小鼠所致肝脏损伤的影响

Effect of Angelica Polysaccharide on liver injury induced by cisplatin chemotherapy in H22 ascites tumor mice

目的:研究当归多糖对顺铂化疗H22腹水瘤小鼠所致肝脏损伤的影响。方法:从90只雄性SPF级昆明小鼠中随机选取12只小鼠设为空白组,剩余小鼠全部腹腔注射H22细胞,7天后腹水瘤模型制备成功,剔除腹水过多和过少的腹水瘤小鼠后,随机分为模型组、顺铂治疗组、顺铂联合当归多糖低剂量组(25mg/kg)、顺铂联合当归多糖中剂量组(50mg/kg)、顺铂联合当归多糖高剂量组(100mg/kg),每组12只。每3天腹腔注射一次0.2ml/只顺铂(2.0mg/kg),当归多糖每天灌胃1次,每只0.4ml;每2天测量并记录各组小鼠体重,3周后,采血并处死小鼠。检测各组小鼠肝脏指数、肝脏功能、血常规的变化,倒置显微镜观察各组小鼠肝脏病理变化,并进行病理评分,Western Blot检测各组小鼠肝脏组织中凋亡相关蛋白Bax以及Bcl-2的表达情况。结果:与空白组和模型组小鼠比较,顺铂治疗组小鼠的体重及肝脏指数降低,AST、ALT含量升高,WBC、RBC、PLT明显降低,Bax表达明显上调,Bcl-2的表达显著下调;HE染色可见肝细胞核固缩,肝细胞核缩小、部分消失。与顺铂治疗组小鼠比较,顺铂联合当归多糖低剂量组(25mg/kg)、顺铂联合当归多糖中剂量组(50mg/kg)、顺铂联合当归多糖高剂量组(100mg/kg)小鼠的体重及肝脏指数有所升高,AST、ALT含量降低,WBC、RBC、PLT明显升高,Bax表达下调,Bcl-2表达升高;HE染色可见到固缩的肝细胞核减轻,细胞排列逐渐接近正常。结论:当归多糖可减轻顺铂化疗H22腹水瘤小鼠时所致的肝脏损伤,其机制可能是通过升高WBC、RBC、PLT来改善肝脏功能、并降低蛋白Bax、升高Bcl-2的表达来实现的。

Objective： To study the effect of Angelica Polysaccharide on liver injury induced by cisplatin chemotherapy in H22 ascites tumor-bearing mice. Methods： 12 mice from 90 male SPF Kunming mice were chosen randomly as the control group,and remaining mice were intraperitoneally injected H22 cells,then ascites tumor models had been successfully established 7 days later. Ascites tumor mice were randomly divided into the model group,Cisplatin group,low dose of Cisplatin combined with angelica polysaccharide（25 mg/kg） group,middle dose of Cisplatin combined with angelica polysaccharide（50 mg/kg） group,high dose of Cisplatin combined with angelica polysaccharide（100 mg/kg） group,with 12 mice in each group,after mice with too many or too few of ascites tumors were excluded. 2. 0 mg/kg Cisplatin was intraperitoneally injected once every 3 days with the dose of 0. 2 ml/mouse,and angelica polysaccharide was intraperitoneally injected once every day with the dose of 0. 4 ml/mouse. The body weight in each group was measured every 2 days,mice were killed and blood was collected after3 weeks. Changes of the liver index,the liver function and blood routine were detected,and pathological changes of the liver were observed by inverted microscope,pathological scores were also performed. Western Blot was used to detect expressions of apoptosis related protein Bax and Bcl-2 in each group. Results： Compared with the control group and model group,the body weight and liver index in Cisplatin group decreased,contents of AST and ALT increased,the number of WBC,RBC and PLT significantly decreased. The expression of Bax was significantly increased,and the expression of Bcl-2 was significantly down,differences were statistically significant. HE staining showed that liver karyopyknosis appeared,liver nuclei shrunk and partially disappeared. Compared with Cisplatin group,in low,middle,high doses of Cisplatin combined with angelica polysaccharide groups,body weights and liver indexes increased,contents of AST and ALT decreased,the number of WBC,RBC and PLT significantly increased,the expression of Bax was significantly decreased,and the expression of Bcl-2 significantly increased,differences were statistically significant. HE staining showed that liver karyopyknosis alleviated,cells arrangement gradually approached normal. Conclusion： Angelica polysaccharide can reduce liver injury induced by cisplatin chemotherapy in H22 ascites tumor-bearing mice,and the mechanism maybe improve the liver function through increasing the number of WBC,RBC and PLT,and decreasing the expression of protein Bax and increasing Bcl-2.