当归贝母苦参丸对顺铂化疗H22荷瘤小鼠的抑瘤作用及对血清HIF-1α和LDH的影响

Tumor-inhibitory role of Danggui Beimu Kushen Pills in cisplatin chemotherapy to H22 tumor-bearing mice and effect on serum levels of HIF-1α and LDH

目的探讨当归贝母苦参丸(当归、浙贝母和苦参)对顺铂化疗H22荷瘤小鼠的抑瘤作用及其对血清低氧诱导因子HIF-1α和乳酸脱氢酶(LDH)的影响。方法将雌雄各32只荷H22肝癌移植瘤小鼠随机分为模型组、顺铂组、当归贝母苦参丸组、当归贝母苦参丸与顺铂联合组,另设正常对照组(n=16)。观察各组小鼠一般状况,检测有效体质量变化及抑瘤率、q值、肿瘤指数、肝脏、脾脏、胸腺、和肾脏的器官指数。血常规检测白细胞计数,ELISA检测血清HIF-1α的水平,血生化检测LDH活力。结果当归贝母苦参丸组与联合组的一般状况优于模型组和顺铂组;各治疗组瘤体质量均低于模型组瘤体质量(P<0.05),联合组的抑瘤率高于单用当归贝母苦参丸或顺铂的抑瘤率,联合用药疗效具有相加效应;当归贝母苦参丸组有效体质量增加、脾脏和胸腺指数高于顺铂组(P<0.05);当归贝母苦参丸组和联合组血清HIF-1α水平低于模型组(P<0.05),两组血清LDH活性低于顺铂组(P<0.05)。结论当归贝母苦参丸具有抑瘤作用和对顺铂化疗的增效减毒作用,抑瘤作用可能与降低小鼠血清中HIF-1α水平和降低顺铂引起的LDH活性升高所致的组织损伤。

AIM To study tumor-inhibitory role of Danggui Beimu Kushen Pills（ Angelicae sinensis Radix,Fritillariae thunbergii Bulbus,Sophorae flavescentis Radix） in cisplatin chemotherapy to H22 tumor-bearing mice and its effect on serum levels of hypoxia inducible factor 1α（ HIF-1α） and lactate dehydrogenase（ LDH）.METHODS H22 hepatocarcinoma xenograft models were established to be randomly divided into the model group,cisplatin group,Danggui Beimu Kushen Pills group,Danggui Beimu Kushen Pills plus cisplatin group. Normal group was also established. General state of KM mice was observed. Effective changes of body weight,tumor inhibition rate,q value,as well as indexes of tumor,liver,spleen,kidney,and thymus were calculated. Blood routine was done to determine white blood cell count. Serum HIF-1α and LDH were determined by ELISA and biochemistry method,respectively. RESULTS The general state of Danggui Beimu Kushen Pills plus cisplatin group and Danggui Beimu Kushen Pills group was better than that of cisplatin group. The effective body weight of Danggui Beimu Kushen Pills group and Danggui Beimu Kushen Pills plus cisplatin group was higher than that of cisplatin group（ P〈 0. 05）. The mass of tumor in Danggui Beimu Kushen Pills group,cisplatin group,and Danggui Beimu Kushen Pills plus cisplatin group was lighter than that in the model group（ P 〈0. 05）. The tumor inhibiting rate of Danggui Beimu Kushen Pills plus cisplatin group was better than that of both Danggui Beimu Kushen Pills group and cisplatin group. Danggui Beimu Kushen Pills and cisplatin had cooperative effect. The indexes of spleen and thymus in Danggui Beimu Kushen Pills group were higher than those in cisplatin group（ P 〈 0. 05）.The numbers of Neutro-phils and monocyte in Danggui Beimu Kushen Pills group and Danggui Beimu Kushen Pills plus cisplatin group were higher than those in cisplatin group（ P〈 0. 05）. Serum level of HIF-1α in model group was higher than that of Danggui Beimu Kushen Pills group and Danggui Beimu Kushen Pills plus cisplatin group.Cisplatin group showed higher LDH activity than Danggui Beimu Kushen Pills group and Danggui Beimu Kushen Pills plus cisplatin group（ P 〈 0. 05）. CONCLUSION Danggui Beimu Kushen Pills can inhibit the growth of transplanted tumor in mice and add positive effect to cisplatin without a little side effect. Its tumor inhibitory effect might be related to reducing serum HIF-1α and lowering the tissue injury from increased activity of LDH caused by cisplatin.