CAJ | 학술논문

目的:探讨银杏叶提取物(extract 761 from Ginkgo biloba,EGb761)对黄曲霉毒素B_1(aflatoxin B_1,AFB_1)在大鼠体内代谢的影响.方法:经AFB_1和EGb761不同处理,获得AFB_1组、AFB_1+EGb761组和空白对照组3组大鼠,分别于实验第14、28及42周给予抽血及肝活检,并于第64周全部处死.观察大鼠肝癌发生率,用分光光度法检测肝组织Ⅰ相酶CYP450和Ⅱ相酶GST活性,用高效液相色谱法检测血清AFB_1-赖氨酸加合物水平,以及应用免疫组织化学法检测8-羟基脱氧鸟嘌呤核苷(8-hydroxydeoxyguanosine,8-OHdG)蛋白表达情况.结果:肝癌诱发率在AFB_1+EGb761组明显低于AFB_1组(P<0.001),而对照组无肿瘤发生;EGb761对Ⅰ相代谢酶CYP450及Ⅱ相代谢酶GST活性无明显影响.血清AFB_1-赖氨酸加合物的最高水平(4 356.01 pg/mg albumin)发生于实验第14周的AFB_1组.在实验第14、42周时EGB761显著抑制了血清AFB_1-赖氨酸加合物的形成,抑制率分别为13.07% (P＝0.033)、73.63% (P＝0.002).在各检测点的8-OHdG蛋白表达强度显示,AFB_1+Egb 761组均显著低于AFB_1组(P<0.05).结论:EGb761阻断AFB_1致肝癌发生的主要机制可能不完全是通过影响肝脏Ⅰ、Ⅱ相代谢酶活性的途径实现的.EGb761能够抑制AFB_1-赖氨酸加合物的形成,降低8-OHdG蛋白的表达,减轻DNA的氧化损伤,这可能是其最终抑制或延缓AFB_1诱发肝癌发生、发展的机制之一.
목적:탐토은행협제취물(extract 761 from Ginkgo biloba,EGb761)대황곡매독소B_1(aflatoxin B_1,AFB_1)재대서체내대사적영향.방법:경AFB_1화EGb761불동처리,획득AFB_1조、AFB_1+EGb761조화공백대조조3조대서,분별우실험제14、28급42주급여추혈급간활검,병우제64주전부처사.관찰대서간암발생솔,용분광광도법검측간조직Ⅰ상매CYP450화Ⅱ상매GST활성,용고효액상색보법검측혈청AFB_1-뢰안산가합물수평,이급응용면역조직화학법검측8-간기탈양조표령핵감(8-hydroxydeoxyguanosine,8-OHdG)단백표체정황.결과:간암유발솔재AFB_1+EGb761조명현저우AFB_1조(P<0.001),이대조조무종류발생;EGb761대Ⅰ상대사매CYP450급Ⅱ상대사매GST활성무명현영향.혈청AFB_1-뢰안산가합물적최고수평(4 356.01 pg/mg albumin)발생우실험제14주적AFB_1조.재실험제14、42주시EGB761현저억제료혈청AFB_1-뢰안산가합물적형성,억제솔분별위13.07% (P＝0.033)、73.63% (P＝0.002).재각검측점적8-OHdG단백표체강도현시,AFB_1+Egb 761조균현저저우AFB_1조(P<0.05).결론:EGb761조단AFB_1치간암발생적주요궤제가능불완전시통과영향간장Ⅰ、Ⅱ상대사매활성적도경실현적.EGb761능구억제AFB_1-뢰안산가합물적형성,강저8-OHdG단백적표체,감경DNA적양화손상,저가능시기최종억제혹연완AFB_1유발간암발생、발전적궤제지일.
Objective:To study the effect of Ginkgo biloba extract (EGb761) on metabolism of aflatoxin B_1(AFB_1) in Wistar rats. Methods:Seventy one Wistar rats were divided into three groups at random: group A (AFB_1 group), group B (AFB_1+EGb761 group), and group C (control group). The rats in groups A and B were given AFB_1(intraperitoneal injection, 100-200 μg/ kg body weight, 1-3 times/week). The rats in group B were fed the food containing EGb761 while the rats in groups A and C were given normal food. Blood samples were collected and liver biopsy was performed on the 14th, 28th and 42nd week. All the rats were sacrificed at the 64th week. The incidence of hepatoma was observed. The hepatic phase Ⅰ drug-metabolizing enzyme CYP450 and phase Ⅱ enzyme GST were detected by spectrometry. The serum AFB_1-lysine adduct was determined by high performance liquid chromatography (HPLC). The expression of 8-hydroxydeoxyguanosine(8-OHdG) was measured by immunohistochemistry. Results:The incidence of hepatocellular carcinoma (HCC) in group B was significantly lower than that in group A (26.92% vs 76.00%,P<0.001). No hepatocellular carcinoma developed in group C. EGb761 had no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB_1-lysine adduct reached the peak (4 356.01 pg/mg albumin) at the 14th week in group A. EGb761 significantly inhibited the formation of AFB_1-lysine adducts in serum by 13.07% at the 14th week (P＝0.033), and 73.63% at the 42nd week (P＝0.002). The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week (P<0.05). Conclusion:The main mechanism underlying the effect of EGb761 in blocking hepatogenesis induced by AFB_1 may not be fully related with its influence on the activity of liver phase Ⅰ and phase Ⅱ metabolizing enzymes. EGb761 inhibites the production of AFB_1-lysine addcuts, decreases the expression of 8-OHdG protein, and finally alleviates the DNA oxidative injury, which may be one of the mechanisms for the effects of EGb761 in inhibiting or delaying hepatogenesis induced by AFB_1.