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中药黄芪散对 N-亚硝二甲胺诱导肝癌生成过程中能量代谢酶表达的调控

Modulation of energy metabolic enzyme expression in N-nitrosodiethylamine-mediated hepatocarcinogenesis by Chinese herbs, Huqi San.

机构信息

Pathophysiological Department, Capital Medical University, You An Men, Beijing 100069, P.R. China.

出版信息

Biofactors. 2008;34(4):303-12. doi: 10.3233/BIO-2009-1084.

Abstract

AIM

To elucidate the anticancer mechanism of Huqi San by assessing the expression of G-6-Pase, SDH, ATPase and AFP in N-nitrosodiethylamine-mediated hepatocarcinogenesis in rats.

METHODS

A Solt-Farber two-step test model of hepatocarcino genesis was established by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) in rats to investigate the modifying effects of expression of 6-glucosephosphatase (G-6-Pase), succinodehydrogenase (SDH), adenosine triphosphatase (ATPase) in N-nitrosodiethylamine-mediated hepatocarcinogenesis. Hu Qisan compounded by eight medicinal herbs was prepared in glycoprival granules with wich 0.38 g crude herbs/mL solution was prepared for administration. gamma-Glutamy-transpeptidase (gamma-GT), G-6-Pase, SDH and ATPase were immunohistochemically determined. The activity of alpha-fetoglobulin (AFP) in the livers was measured with Immunofluorescence.

RESULTS

Huqi San treated rats showed significant decrease in areas of gamma-GT positive foci (P< 0.001). On the other hand, the expression of G-6-Pase, SDH and ATPase has obviously altered in Huqi San treated group. The activity of AFP also significantly decreased after the treatment with Huqi San (8 g/kg body weight or 4 g/kg body weight) or total alkali of mistletoe (0.12 g/kg body weight).

CONCLUSIONS

Huqi San can obviously increase these activities of G-6-Pase, SDH and ATPase, and at the same time significantly decrease the expression of gamma-GT and AFP. Therefore, it can obstruct or inhibit the rat's liver preneolastic lesion induced by DEN.

摘要

目的

通过评估 G-6-Pase、SDH、ATPase 和 AFP 在二乙基亚硝胺(DEN)诱导的大鼠肝癌发生中的表达,阐明黄芪散的抗癌机制。

方法

采用二乙基亚硝胺(DEN)和 2-乙酰氨基芴(AAF)两步法建立大鼠肝癌发生的 Solt-Farber 模型,研究黄芪散对 N-亚硝二乙胺(DEN)诱导的肝癌发生中 G-6-Pase、琥珀酸脱氢酶(SDH)、三磷酸腺苷酶(ATPase)表达的修饰作用。由 8 种草药组成的黄芪散制成甘糖酯颗粒,制备浓度为 0.38 g 粗草药/mL 的溶液用于给药。γ-谷氨酰转肽酶(γ-GT)、G-6-Pase、SDH 和 ATPase 用免疫组化法测定。用免疫荧光法测定肝脏中α-胎球蛋白(AFP)的活性。

结果

黄芪散治疗组大鼠的γ-GT 阳性灶面积明显减少(P<0.001)。另一方面,黄芪散治疗组 G-6-Pase、SDH 和 ATPase 的表达也明显改变。黄芪散(8 g/kg 体重或 4 g/kg 体重)或槲寄生总碱(0.12 g/kg 体重)治疗后 AFP 的活性也显著降低。

结论

黄芪散能明显增加 G-6-Pase、SDH 和 ATPase 的活性,同时显著降低γ-GT 和 AFP 的表达。因此,它可以阻止或抑制 DEN 诱导的大鼠肝前病变。

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