环磷酰胺联合柿叶乙酸乙酯部位对H22小鼠瘤组织抗氧化能力及Bcl-2,Bax蛋白表达的影响

目的: 通过研究环磷酰胺(CTX)联合柿叶乙酸乙酯部位(PE)对H22荷瘤小鼠瘤组织的抗氧化作用和对瘤组织凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关x蛋白(Bax)蛋白表达的影响,探讨两药联合应用的效果。 方法: 昆明种小鼠,取H22荷瘤鼠腹水接种于昆明种小鼠右前肢腋窝皮下,建立H22荷瘤小鼠模型,将荷瘤小鼠随机分为模型组,CTX组(0.1 g ·kg^-1),CTX联合PE高、中、低剂量组(2,1,0.5 g ·kg^-1),连续ig给药10 d,处死小鼠后计算抑瘤率,采用金氏q值法判断两者合用的效果,检测瘤组织中超氧化物歧化酶(SOD)活力,丙二醛(MDA)含量,采用免疫组化法检测瘤组织中Bcl-2和Bax蛋白表达情况。 结果: 与模型组比较,各给药组抑瘤率明显升高,SOD水平和Bax蛋白表达均明显升高,MDA水平和Bcl-2蛋白表达明显降低(P<0.05,P<0.01);CTX联合PE各剂量组的抑瘤率均高于CTX组,0.85<q<1.15,两药合用作用相加;与CTX组比较,联合用药各剂量组SOD水平和Bax蛋白表达均升高,MDA水平,Bcl-2蛋白表达及Bcl-2/Bax均降低(P<0.05,P<0.01)。 结论: CTX联合PE能使抑瘤作用相加,其机制可能与两药合用能明显增强H22小鼠机体抗氧化能力,下调Bcl-2蛋白及上调Bax 蛋白的表达有关。

Effect of CTX Combined with Ethyl Acetate Extracts from Persimmon Leaves on Antioxidant Capacity and Bcl-2 and Bax Expressions in H22 Bearing Mice

Objective: To study the antioxidant activity of cyclophosphamide (CTX) combined with ethyl acetate extracts from persimmon leaves (PE) on hepatoma H22 bearing mice and their effect on tumor tissue apoptosis-related proteins Bcl-2 and Bax expressions. Method: Kunming mice were selected and subcutaneously inoculated with H22 tumor at right fore armpit to establish the H22 bearing mouse model. The H22 bearing mice were randomly divided into the model group, the CTX group (0.1 g · kg^-1), the CTX combined with high, middle and low dose PE groups (2, 1, 0.5 g · kg^-1) and were orally given drugs for 10 days. After killing the rats, efforts were made to calculate the anti-tumor rate, detect the combined effect by Jin's formula q, superoxide dismutase(SOD) activity and malonaladehyde(MDA) content in tumor tissues, and analyze Bcl-2 and Bax protein expressions in tumor tissues by immunohistochemistry. Result: Compared with the model group, all treatment groups showed significantly higher tumor inhibition rate, SOD and Bax protein expression and lower MDA and Bcl-2 protein expression (P<0.05, P<0.01). The tumor inhibition rate of CTX combined with PE in each dose group was higher than that of the CTX group, with the Jin's formula q between 0.85 and 1.15, indicating their combined effect. Compared with the CTX group, the SOD activity and bax expression of CTX combined with PE in each dose group increased, but the MAD content, Bcl-2 expression and Bcl-2/Bax ratio decreased (P<0.05, P<0.01). Conclusion: CTX combined with PE had better antitumor effect. Its mechanism is probably related to their combined effect in notably strengthening the antioxidant capacity, down-regulating Bcl-2 expression and up-regulating bax expression of H22 bearing mice.