大蒜素对二甲基亚硝胺诱发的肝纤维化大鼠的保护作用

目的　研究大蒜素对实验性肝纤维化大鼠的保护作用。方法　 SD大鼠随机分为 5组 :正常对照组、模型组(给等量蒸馏水 )、大蒜素 (11、2 2 mg/ kg)组、秋水仙碱 (0 .15 g/ kg)组。二甲基亚硝胺 (DMN)诱发大鼠肝纤维化模型 ,各组在造模开始时 ig给药 ,实验共进行 4 2 d。腹主动脉取血 ,制备血清 ,进行肝功能、血脂、肝细胞病理学检查。结果　大蒜素各组均能明显降低实验性肝纤维化大鼠血清丙氨酸转氨酶 (AL T)、谷草转氨酶 (AST) (P<0 .0 5、0 .0 1)水平 ,以大蒜素 2 2 mg/ kg组作用明显 ,而秋水仙碱对肝功能没有明显的改善作用 (P>0 .0 5 )。大蒜素均能明显降低血清甘油三酯 (TG)、胆固醇 (TC)水平 ,提高血清白蛋白 (AL B)含量。病理学检查结果 ,大蒜素组肝细胞的坏死、空泡变性、出血及脂肪沉积较模型组和秋水仙碱组明显减轻 ,炎症细胞明显减少。电镜检查结果显示 ,大蒜素 11mg/ kg组肝细胞坏死、自溶较模型组明显减轻 ,大蒜素 2 2 mg/ kg组肝细胞接近正常。结论　大蒜素对 DMN所致肝损伤具有保护作用。     

小柴胡汤对鼠实验性肝纤维化的影响

目的:探讨小柴胡汤对鼠肝纤维化的抑制作用及该抑制作用与活性伊东细胞间的相互关系。方法:分别腹腔注射二甲基亚硝基胺和猪血清复制两种肝纤维化动物模型并投予小柴胡汤观察其预防与治疗作用。结果:小柴胡汤可促进肝维生素 A 含量恢复;降低肝胶原含量和明显抑制肝前α-Ⅰ型胶原的基因表达;显著减少Ⅰ、Ⅲ型胶原在肝脏沉积,明显减少。α-平滑肌原纤维阳性的伊东细胞的数目。结论:小柴胡汤可防治鼠肝纤维化的发生与发展。     

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats

Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.     

虫草菌丝提取物干预与治疗二甲基亚硝胺诱导大鼠肝硬化的实验研究

目的 明确虫草菌丝提取物（Cordyceps mycelia extract, CME）对二甲基亚硝胺（dimethylnitrosamine,DMN）诱导大鼠肝硬化的干预与治疗作用。 方法 采用DMN 10 μg/kg 剂量腹腔内注射,每日1次,每周前3日、持续4周的方法制备大鼠肝硬化模型。CME干预实验于造模即日起开始灌胃给药至造模4周末;治疗实验于造模4周、终止造模因素后开始给药至8周末;均以0.74 g/(kg·d)剂量给予CME,每日 1次。分别于造模后3天、2、4、6、8周处死动物取材进行动态效应观察。观测肝组织学、肝组织α平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原(ColⅠ)的免疫组织化学染色、肝羟脯氨酸（Hyp）含量以及肝功能的检测。 结果 与同期模型组比较,CME预防给药后2、4周的血清丙氨酸氨基转移酶（ALT）、血清门冬氨酸氨基转移酶（AST）活性和血清总胆红素（TBIL）含量均显著降低（P<0.05）,血清白蛋白（Alb）含量显著增加（P<0.05）;干预用药4周后的肝Hyp含量显著下降（P<0.05）,胶原纤维增生程度显著减轻（P<0.05）,肝组织内α-SMA、ColⅠ阳性表达显著减少（P<0.05）。与同期模型组比较,治疗给药2周后的血清ALT、AST活性和血清TBIL含量显著降低（P<0.05）,血清Alb含量有所升高(P＞0.05);治疗给药2、4周的肝Hyp含量均显著降低（P<0.05）,胶原纤维增生程度均显著减轻（P<0.05）,肝组织α-SMA表达均显著减少（P<0.05）; 治疗给药4周时肝组织ColⅠ表达显著减少（P<0.05）。 结论 CME既能显著抑制DMN大鼠肝硬化的形成,也可有效促进已成型的DMN大鼠肝硬化的逆转,具有良好的临床应用前景。     

苦杏仁苷对二甲基亚硝胺诱导的大鼠肝纤维化的防治作用

目的：探讨苦杏仁苷对二甲基亚硝胺（DMN）诱导的大鼠肝纤维化的防治作用。方法：采用Wistar雄性大鼠,以腹腔注射DMN诱导大鼠肝纤维化模型。在造模4周后,将造模大鼠按体重分层随机分为模型组、苦杏仁苷组及对照药秋水仙碱组,每组10只,灌胃用药两周后取材。观察检测以下指标：①末次体重、肝脾比值;②肝组织羟脯氨酸含量;③肝功能指标：血清丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、谷胺酰转肽酶（GGT）活性;白蛋白（Alb）、总胆红素（TBil）含量;④肝组织天狼星红染色及HE染色;⑤肝组织脂质过氧化指标：超氧化物歧化酶（SOD）、丙二醛（MDA）、还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）。结果：①模型组大鼠肝组织羟脯氨酸含量与正常组相比显著升高（P〈0.01）;与模型组相比,苦杏仁苷及秋水仙碱治疗组大鼠肝组织羟脯氨酸含量显著降低（P〈0.01）;②天狼星红染色显示模型组大鼠窦周胶原沉积明显,肝小叶间形成较厚汇管区和中央静脉间的纤维间隔,可见较多完整的假小叶,HE染色结果显示模型组大鼠肝细胞水肿明显,汇管区结缔组织有不同程度增生,肝组织中有炎性细胞浸润,窦壁细胞增生明显;苦杏仁苷治疗组和秋水仙碱对照组与模型组相比炎症缓解、胶原纤维增生程度分期显著降低（P〈0.05）;③模型组大鼠血清ALT、AST、GGT活性及TBil含量显著升高,Alb含量显著降低（P〈0.01）;苦杏仁苷组与秋水仙碱组大鼠血清ALT、AST活性显著降低（P〈0.01或P〈0.05）;④与正常组比较,模型组大鼠肝组织SOD活性、GSH含量及GSH-Px活性显著降低,MDA含量显著升高（P〈0.05）;苦杏仁苷能显著升高模型大鼠肝组织GSH活性（P〈0.05）,秋水仙碱则能显著升高GSH、GSH-Px活性。结论：苦杏仁苷对DMN诱导的大鼠肝纤维化有显著改善作用。     

N-nitrosodimethylamine,nitrate and nitrate-reducing microorganisms in human milk

Of 54 milk samples from 54 healthy nursing women analysed for volatile N-nitrosamines, 42 appeared negative. Trace amounts (below the detection limit 0.5 μgl^?1) of N-nitrosodimethylamine were detected in the milk of 10 mothers and two samples contained this compound at 1.1 and 1.2 μgl^?1 respectively. Almost all samples investigated contained nitrate (mean 2.9 ± 2.3 mgl^?1) and nitrate reducing microorganisms (mean 4.2 ± 1.0 log ml^?1). The recent finding of N-nitrosodimethylamine in human milk gives evidence of the continuous endogenous formation of N-nitrosamines.     

The mutagenicity of dialkyl nitrosamines in the salmonella plate assay

N-nitrosodimethylamine (DMN) is not mutagenic in the standard Salmonella plate incorporation assay (Ames test) in the presence of an in vitro metabolic activation system (S-9) derived from rat liver. When the S-9 was derived from Aroclor- or phenobarbital-induced mouse or hamster liver or from uninduced hamster liver, mutagenic activity was observed. Increasing the amount of S-9 above the usual maximum level of 50 μ1 per plate increased the mutagenic response. Similarly, the mutagenicity of N-nitrosodiethylamine (DEN) and N-nitrosodi(n-butyl)amine (DBN) was greater in the presence of hamster liver S-9 than when mouse or rat liver was used. Data are also presented indicating that the ability of rat liver S-9 to mediate the mutagenic activity of DMN in the “preincubation” assay is due to the fact that the various components are present in this assay at several times the concentrations attained in the standard plate incorporation assay.     

Editorial

Mass cultures of primary rat kidney cells were exposed briefly to aqueous solutions of 20 chemicals and their subsequent growth rate and mitotic activity measured. Proximate carcinogens, and some chemicals with a defined inhibitory action biochemically, depressed the growth and division of the cultures. Non-carcinogenic compounds and precarcinogens did not interfere with the subsequent growth rate and mitotic activity of the cultures. It is suggested that the possession of growth inhibitory properties could give an indication of the carcinogenic activity of a chemical on a short-term basis.     

DNA repair synthesis in primary cultures of kidneys from BALB/c and C3H mice treated with dimethylnitrosamine

A combined 'in vivo--in vitro' autoradiographic method was employed to examine the DNA repair induced in the kidney by a single dose of dimethylnitrosamine (DMNA). Unscheduled DNA synthesis was found to be dose-dependent in primary kidney cultures of DMNA-treated mice, and practically not detectable in controls. Its amount was positively correlated with the different susceptibility of C3H and BALB/c mice to kidney tumor induction by DMNA. This experimental model appears sensitive and able to provide repeatable results. It may be useful to detect the organotropic activity of a carcinogen toward the kidney.     

丹参提取物对CCl4和DMN诱导的大鼠肝纤维化的影响

分别采用四氯化碳和二甲基亚硝胺诱导的大鼠肝纤维化模型,以秋水仙碱和丹参作对照,通过肝组织病理学及Ⅰ、Ⅲ型胶原免疫组化观察,肝组织羟脯氨酸、丙二醛及血清肝功能部分指标检测,探讨丹提取物和治疗肝纤维化的效果及部分作用机理。