摘要
目的研究草苁蓉环烯醚萜苷(iridoid glucosides from Boschniakia rosscica, IGBR)对二乙基亚硝胺(diethylnitrosamine, DEN)诱导的大鼠肝癌前病变的肝脏组织匀浆及线粒体的标志酶及抗氧化酶活力的影响,进而探索其抗化学致癌的可能机制。
方法将60只Wistar雄性大鼠随机分为5个组,各组为12只,分别为正常对照组(Saline-BD-PH)、模型组(DEN-AAF-PH)、草苁蓉环烯醚萜苷低剂量组(DEN-AAF+125mg/kg IGBR-PH)、草苁蓉环烯醚萜苷中剂量组(DEN-AAF+250mg/kg IGBR-PH)、草苁蓉环烯醚萜苷高剂量组(DEN-AAF+500mg/kg IGBR-PH)。模型组和草苁蓉环烯醚萜苷组按照Solt-Farber氏法制作大鼠肝癌前病变模型。实验开始第一周起给大鼠经腹腔注射DEN200mg/kg,第二周至第八周模型组和各草苁蓉环烯醚萜苷组给予0.008%乙酰氨基芴,同时草苁蓉环烯醚萜苷组各组灌胃草苁蓉环烯醚萜苷。第三周后进行肝部分切除术。第八周后处死大鼠,观察大鼠肝脏形态变化,制作肝脏组织匀浆及肝脏线粒体,测定天门冬氨酸氨基转肽酶(aspartate transaminase, AST)、丙氨酸氨基转肽酶(alanine transaminase, ALT)、谷酰胺转肽酶(γ-glutamyl transpeptidase,γ-GT)、过氧化氢酶(catalase, CAT)、超氧化物岐化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-PX)、谷胱甘肽-S-转移酶活性(glutathione-S-transferase,GST)及丙二醛(malondialdehyde,MDA)含量。
结果1.草苁蓉环烯醚萜苷促进大鼠食欲,能改善大鼠的精神状态、皮毛色泽。2.模型组肝癌前病变时大鼠肝脏组织匀浆AST、ALT、γ-GT、GST活性和MDA含量显著高于正常对照组,SOD、CAT、GSH-PX活性显著低于正常对照组;肝脏线粒体GST活性和MDA含量显著高于正常对照组,SOD、CAT、GSH-PX活性显著低于正常对照组。草苁蓉环烯醚萜苷组肝脏组织匀浆γ-GT、ALT、AST、GST活性和MDA含量显著降低,SOD、CAT、GSH-PX活性显著回升;肝脏线粒体GST活性和MDA含量显著降低,SOD、CAT、GSH-PX活性显著回升。
结论草苁蓉环烯醚萜苷对二乙基亚硝胺诱导的大鼠肝癌前病变肝脏组织具有明显的保护作用,防止脂质过氧化和增强抗氧化酶活性。
Objective:To study the effect of iridoid glucosides from Boschniakia rossica (IGBR) on liver tissue homogenate、Mitochondrial Marker Enzyme and antioxidative enzymes of rats with hepatic preneoplasia induced by diethylnitrosamine (DEN) and investigatc the possible mechanism of its anti-tumor.
Methods:Sixty male Wistar rats were randomly assigned into five groups, each groupHave 12 rats. control group [saline-basal diet (BD)-partial hepatectecomy (PH)], model group[(DEN-acetylaminoflofluorene(AAF)-PH)], IGBR low dose group (DEN-AAF+125mg/kgIGBR-PH), IGBR medium dose group (DEN-AAF+250mg/kg IGBR-PH) and IGBR high dose group (DEN-AAF+500mg/kg IGBR-PH). Observe the change of hepatic in rats, and make liver tissue homogenate and Hepatic mitochondria after the eight week execute rats, determination of the content of aspartate amino-transferdse (AST), alanine trasaminase (ALT), y-glutamy transpeptidase (y-GT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST), and malondialdehyde (MDA).
Result:IGBR obviously improved the weigh gain, mental state, color pattern for rats. the rats in model group liver tissue homogenate AST、ALT、γ-GT、GST activity and MDA level were increased,and the SOD,CAT, GSH-PX activities were dereased in model group before hepatic preneoplastic; compare with model group, the mitochondria in liver GST activity and MDA content were increased and SOD、CAT、GSH-PX activity were decreased. IGBR liver tissue homogenate reduced the activities of y-GT、ALT、AST、GST and MDA content, SOD、CAT、GSH-PX activity firm up; GST activity and MDA content were reduced, and SOD、CAT、GSH-PX activity have firm up in liver tissue homogenate.
Conclusion:IGBR exhibited obvious protection effect on DEN induced rats hepatic preneoplastic lesions, prevent its lipid peroxidation and enhance antioxidant enzymes activity.
引文
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