鹿茸对小鼠急性肝损伤的修复作用及相关机理研究
|
摘要
急性肝损伤是临床常见、多发的肝脏病患,是各种肝病共同的病理基础,其病理特点主要为肝细胞变性、坏死,甚至凋亡,其长期存在往往导致肝纤维化,甚至是肝硬化、肝癌发生的重要的使动因素。因此防治肝损伤是临床肝病治疗的主要环节之一,及时控制肝损伤的发生和发展对治疗肝病将有重要的临床意义。鹿茸含有多种生物活性成分,有广泛的药理作用和医疗保健功能。在现代医疗实践中,以鹿茸为主要原材料制作的药剂已经应用于多种疾病的治疗,并取得良好的效果,但在肝病治疗中尚未得以普遍应用。如果将鹿茸应用到肝病的治疗和保健中,不仅可解决医学上一大难题,而且也可以为鹿茸的开发带来巨大的经济效益和社会效益。
目前研究已经揭示鹿茸对肝损伤确有一定的修复作用,但对其抗肝损伤的具体作用及作用机理尚不十分清楚。本研究以小鼠为实验对象,利用CCl_4、APAP、56°白酒以及BCG+LPS几种毒物制造化学性、药物性、酒精性和免疫性四种不同类型的急性肝损伤模型,通过监测血清中ALT、AST、TP、ALB、TBil、TG的浓度和肝组织匀浆中MDA、SOD、NO、ADH的含量,来研究以马鹿茸为原料制备的鹿茸粉和鹿茸醇提物对不同类型肝损伤的修复作用及相关机理,旨在从肝细胞损伤、肝脏合成贮备功能、分泌排泄功能、脂代谢功能及脂质过氧化几个方面阐明鹿茸对肝脏的保护作用及部分作用机理,为充分开发鹿茸新的药用价值,研制鹿茸抗肝损伤的新型医疗保健药物提供生化药理学基础。
1.鹿茸对CCl_4所致化学性肝损伤修复作用的研究结果表明:
对肝细胞损伤的保护作用方面,鹿茸醇提物1.0g/kg、2.0g/kg均可以明显降低ALT、AST的含量(P＜0.01),其中醇提物2.0g/kg将ALT由204.08±72.00U/L降至55.21±7.93U/L,AST由234.77±7.71U/L降至80.57±10.80U/L,其降酶作用与联苯双酯(71.25±14.06、79.83±11.02U/L)相当。在提高肝脏蛋白合成储备功能方面,鹿茸醇提物1.0g/kg、2.0g/kg均能明显提高血清TP(56.94±5.96、59.90±3.89g/L)及ALB(31.80±0.92、31.30±0.72g/L)含量(P＜0.01),作用效果优于联苯双酯(37.94±5.80、29.18±2.78g/L),而鹿茸粉效果不显著。对肝脏排泄分泌功能的改善方面,鹿茸醇提物2.0g/kg能将血清TBil明显降低至6.35±0.22μmol/L(P＜0.01),效果与联苯双酯(6.33±0.29μmol/L)相当,而鹿茸醇提物1.0g/kg稍差(P＜0.05)。改善肝脏脂代谢功能方面,各治疗组均能降低血清TG含量,其中鹿茸醇提物2.0g/kg可将TG由1.03±0.09mmol/L降至0.70±0.12mmol/L,作用效果明显(P＜0.05)且与联苯双酯(0.87±0.06mmol/L)相当。在对抗肝脏自由基的脂质过氧化方面,鹿茸醇提物能显著提高SOD活力、降低MDA和NO水平(P＜0.01),鹿茸醇提物2.0g/kg作用效果稍好,可将SOD活力提高至78.75±0.56U/mgprot,MDA和NO含量降低至0.93±0.07nmol/mg和40.82±3.73umol/L,而鹿茸粉效果较差。此外,鹿茸能显著降低肝损伤小鼠的肝重系数(P＜0.01),醇提物1.0g/kg组肝重系数为5.01±0.12,其作用效果较2.0g/kg组(5.16±0.07)稍好,但差异不明显。
2.鹿茸对APAP所致药物性肝损伤修复作用的研究结果表明:
对受损肝细胞的保护作用方面,鹿茸醇提物2.0g/kg将ALT、AST分别降至38.38±2.19U/L、36.75±0.92U/L,作用效果优于1.0g/kg(41.67±11.56U/L、56.67±8.09U/L)。在蛋白合成储备功能方面,各治疗组TP含量均有小幅升高,其中醇提物1.0g/kg组TP升高至38.17±0.76g/L,鹿茸粉组升高至27.17±0.61g/L,两组效果均显著(P＜0.05),而ALB含量升高幅度较大,醇提物2.0g/kg治疗效果最好(P＜0.01),其ALB含量高达29.86±1.00g/L。在改善肝脏的胆汁瘀滞程度方面,各治疗组TBil含量均明显降低(P＜0.01),其中鹿茸醇提物2.0g/kg可将TBil降低至8.59±0.27μmol/L,作用效果优于醇提物1.0g/kg,但均低于联苯双酯(8.27±0.38μmol/L)。对脂代谢功能的调节方面,各治疗组TG含量都有大幅度的降低(P＜0.01),其中鹿茸醇提物2.0g/kg的疗效最好,其TG由1.68±0.05mmol/L降至0.86±0.03mmol/L,低于联苯双酯(0.61±0.02mmol/L)。鹿茸各治疗组均能在一定程度上提高SOD活力,降低NO和MDA水平,抑制APAP所致受损肝脏的脂质过氧化反应,但均未达到联苯双酯组中SOD(77.56±2.18U/mgprot)、MDA(0.77±0.06nmol/mg)和NO(45.24±4.39umol/L)水平。鹿茸还能能显著降低APAP急性肝损伤小鼠的肝重系数,其中醇提物2.0g/kg组与模型组相比差异极显著(P＜0.01),将肝重系数由6.52±0.23降至5.64±0.11,作用效果较1.0g/kg的明显。
3.鹿茸对酒精性肝损伤修复作用的研究结果表明:
对减轻肝细胞的损伤程度方面,各组ALT、AST均有不同程度的降低,其中鹿茸醇提物2.0g/kg对AST的降低效果极显著(P＜0.01),可将AST由56.00±2.31U/L降至36.42±1.45U/L,结合ALT和AST综合判断,鹿茸醇提物2.0g/kg效果最佳。对改善肝脏的合成储备功能方面研究发现,鹿茸对促进TP的合成作用不显著,而能显著增加肝脏对ALB的合成功能(P＜0.01),鹿茸醇提物2.0g/kg作用效果较好,能将其提高至28.71±1.12g/L,仅次于联苯双酯的29.15±0.95g/L。在肝脏对TBil的摄取、结合和排泄能力方面,鹿茸缓解急性酒精肝损伤小鼠肝脏胆汁瘀滞的程度,给药后各组TBil含量均大幅降低(P＜0.01),其中鹿茸醇提物1.0g/kg作用效果最好,使TBil达到10.99±1.55μmol/L,仅次于联苯双酯(9.46±0.11μmol/L)。鹿茸能有效抑制脂肪变性,调整脂代谢功能,鹿茸醇提物1.0g/kg组和鹿茸粉组可将TG降低至0.80±0.07mmo/L和0.94±0.02mmol/L,作用效果较差,而鹿茸醇提物2.0g/kg能将TG降低至0.65±0.28mmol/L,作用效果极显著(P＜0.01),且与联苯双酯(0.61±0.07mmol/L)相当。在抗急性酒精肝损伤脂质过氧化方面,鹿茸粉作用效果低于鹿茸醇提物,其中醇提物2.0g/kg效果最好,可将SOD活性提高至73.20±0.60U/mgprot,MDA和NO含量降低至1.05±0.07nmol/mg和50.00±3.19umol/L,但均低于联苯双酯。在肝脏对酒精的代谢能力方面,鹿茸能明显增加肝脏ADH活性,与模型组相比,鹿茸粉可使ADH活性由0.93±0.03U/mg提高至1.11±0.04U/mg(P＜0.05),其作用效果明显低于鹿茸醇提物1.0g/kg组的1.42±0.06U/mg和2.0g/kg组的1.52±0.03U/mg(P＜0.01)。此外,鹿茸能有效抑制大量饮酒造成的肝脏重量的增加,鹿茸醇提物2.0g/kg作用效果最好(P＜0.01),将肝重系数降至4.99±0.23,作用与联苯双酯相当。
4.鹿茸对BCG和LPS联合所致免疫性肝损伤修复作用的研究结果表明:
对肝细胞损伤的保护作用方面,鹿茸给药后ALT、AST均不同程度降低,鹿茸醇提物2.0g/kg可将ALT、AST分别由43.79±1.51U/L、53.50±1.72U/L降至33.33±2.78U/L、39.50±0.93U/L,其对于免疫性肝损伤的保护作用较1.0g/kg稍好而与联苯双酯相当,鹿茸粉(37.17±2.20U/L、50.83±5.92U/L)作用最差。在促进肝脏蛋白质的合成代谢功能方面,各组TP和ALB均有不同程度的提高,鹿茸醇提物效果高于鹿茸粉,其中醇提物2.0g/kg效果较好,可将TP、ALB分别提高至36.81±0.55g/L、26.62±0.54g/L,但低于联苯双酯(38.35±1.31g/L、27.61±0.65 g/L)。在改善摄取、转化和排泄TBil的能力方面,给药后各组TBil含量均极显著降低(P＜0.01),鹿茸醇提物2.0g/kg将TBil由17.42±0.74μmol/L降低至8.82±0.20μmol/L,作用效果优于其它组,仅次于联苯双酯(7.85±0.51μmol/L)。在调节脂代谢功能方面,各组TG含量在用药后均明显降低,鹿茸醇提物2.0g/kg降低幅度最大(P＜0.01),由1.23±0.07mmo/L降至0.87±0.03mmo/L,效果较联苯双酯(0.79±0.03mmo/L)稍差。对抑制脂质过氧化方面,鹿茸粉和鹿茸醇提物1.0g/kg提高SOD活力的效果较好,可使SOD值达到75.67±1.63U/mgprot和75.57±1.88U/mgprot,鹿茸醇提物降低MDA的效果优于鹿茸粉,其中醇提物2.0g/kg(1.22±0.07nmol/mg)效果略高于1.0g/kg(1.39±0.10 nmol/mg),而NO的降低效果以鹿茸醇提物1.0g/kg效果最为理想,由61.22±5.14umol/L降低至40.82±6.56umol/L,根据MDA、SOD和NO综合分析,鹿茸醇提物1.0g/kg抗脂质过氧化反应的效果较好,但较联苯双酯稍差。此外,鹿茸能抑制免疫性肝损伤造成的肝脏重量的增加,鹿茸粉效果最差,仅由6.22±0.10降至5.97±0.07,鹿茸醇提物2.0g/kg效果较好(P＜0.01),可将达5.74±0.10,但效果低于联苯双酯(5.61±0.11)。
The acute liver damage was a kind of common pathological changes of various liver diseases.A characteristic feature of the pathology was hepatocyte degeneration,necrosis, even apoptosis.Its long-term existence always leaded to hepatic fibrosis,cirrhosis and hepatoma.Therefore,preventing and curing liver damage were the key points of treating clinical liver diseases.Controlling the liver damage in time was particularly important to cure the liver diseases.Velvet has extensive pharmacological action and medical care function.In modern medical practice,the medicines with velvet as its main raw materials gained good effects on treating many diseases.But velvet wasn't used to treat the liver disease.If velvet could be applied to the treatment of liver diseases and the health care,that it could not only resolve a difficult medical problem,but also bring huge economic benefit and the social effect.Some studies showed that velvet had certain repair action for the liver damage,but the action mechanism was still not very clear.
In this study,we dealt the rats with CCl_4、APAP、alcohol and BCG+LPS,established the model of acute liver damage,such as chemical,medicamentosa and immune liver damage.By measuring the content of ALT、AST、TP、ALB、TBil、TG in serum and MDA、SOD、NO、ADH in liver homogenate,expounded the effects and mechanism of velvet powder and the EAV(extract by alcohol from velvet) for the liver damage,finally it could build the foundation of biochemistry and pharmacology for anti-liver damage of velvet.
1.The main results obtained from studies on the repair effects of velvet for the chemical liver damage are as follows:
In terms of protecting the liver cell damage,the EAV(1.0g/kg and 2.0g/kg) could reduce the content of ALT and AST in serum(P＜0.01) obviously.The rats were treated with EAV(2.0g/kg),then the content of ALT was reduced from 204.08±72.00U/L to 55.21±7.93U/L,and the content of AST was reduced from 234.77±7.71U/L to 80.57±10.80U/L;the same effects existed between BIF(71.25±14.06、79.83±11.02U/L ) and EAV(2.0g/kg).In terms of enhancing the function of protein synthesis and reserve, EAV(1.0g/kg and 2.0g/kg) could increase the content of TP(56.94±5.96、59.90±3.89g/L) and ALB(31.80±0.92、31.30±0.72g/L) in serum obviously(P＜0.01),the protective effects was superior to the BIF(37.94±5.80、29.18±2.78g/L);but the effects of velvet powder was not prominent.In terms of improving the liver excretory ability,EAV(2.0g/kg) could reduce the content of TBil(6.35±0.22μmol/L) obviously(P＜0.01) obviously,its effects were as good as BIF(6.33±0.29μmol/L);but the EAV(1.0g/kg) was a little worse(P＜0.05).In terms of improving the liver fat metabolism,the content of TG in each treatment group were reduced;the EAV(2.0g/kg) could reduce the content of TG form 1.03±0.09mmol/L to 0.70±0.12mmol/L,the same effects occurred between BIF(0.87±0.06mmol/L) and EAV(2.0g/kg).For reducing lipid peroxidation of free radicals in liver,the EAV could enhance the vitality of SOD obviously,and reduce the level of MDA and NO(P＜0.01);the EAV(2.0g/kg) could increase the content of SOD(78.75±0.56U/mgprot),and reduce the content of MDA(0.93±0.07nmol/mg) and NO(40.82±3.73umol/L);but the effects of velvet powder was bad.Besides these,velvet could reduce the rat's liver weight coefficient obviously(P＜0.01),but the difference was not significant in each group.
2.The main results obtained from studies on the repair effects of velvet for the medicamentosa liver damage by APAP are as follows:
For protecting the liver's damaged cell,EAV(2.0g/kg) could reduce the content of ALT(38.38±2.19U/L) and AST(36.75±0.92U/L),its effects were better than that of EAV(1.0g/kg).For enhancing the function of protein synthesis and reserve,the content of TP in each treatment group had a small rise;the difference between the effects(38.17±0.76g/L) of EAV(1.0g/kg)and that(27.17±0.61g/L) of velvet powder was significant;the content of ALB had a big rise,EAV(2.0g/kg) remarkable enhanced ALB's content(29.86±1.00g/L),its effects were the best(P＜0.01).For improving cholestasis of liver,the content of TBil reduced obviously,the effects of BIF(8.27±0.38μmol/L) were better than that(8.59±0.27μmol/L) of EAV(2.0g/kg).For adjusting lipid metabolism,the level of TG in each treatment group was reduced a lot(P＜0.01).EAV(2.0g/kg) reduced TG's level from 1.68±0.05mmol/L to 0.86±0.03mmol/L,the level was lower than BIF(0.61±0.02mmol/L).Velvet could enhance the vitality of SOD in each treatment group, and reduce the level of NO and MDA;inhibit the lipid per-oxidization of damaged liver of rats dealt with APAP,but their effects were worse than BIF.Velvet could reduce the rat's liver weight coefficient obviously,EAV(2.0g/kg) was the better than EAV(1.0g/kg),it could reduce the liver weight coefficient from 6.52±0.23 to 5.64±0.11.
3.The main results obtained from studies on the repair effects of velvet for the alcoholic liver damage are as follows:
For alleviating the liver's damaged cell,the levels of ALT、AST all reduced, EAV(2.0g/kg) reduced the content of AST from 56.00±2.31U/L to 36.42±1.45U/L very significantly,its effects were the best.For enhancing protein synthesis and reserve of liver, velvet could not improved TP synthesis remarkably,but could improved ALB synthesis evidently(P＜0.01);but the remedial ability of EAV(2.0g/kg) was worse than BIF(29.15±0.95g/L).For adjusting the ability of liver with TBil ingested、combined and excreted,velvet could alleviate cholestasis of liver,the content of TBil was reduced in each treatment group obviously(P＜0.01) after dealt with velvet;the effects of BIF(9.46±0.11μmol/L) were better than EAV(1.0g/kg),was the best.Velvet could inhibit fatty degeneration and adjust its metabolism;the effects were good by BIF(0.61±0.07mmol/L) and EAV(2.0g/kg),the effects surpassed EAV(1.0g/kg) and velvet powder(0.94±0.02mmol/L) in remedial ability.For acuted lipid per-oxidation by alcohol in damaged liver,remedial ability of EAV(1.0g/kg、2.0g/kg) was better than velvet powder,EAV(2.0g/kg) could adjust the vitality of SOD(73.20±0.60U/mgprot),and reduce the level of MDA(1.05±0.07nmol/mg) and NO(50.00±3.19umol/L);but BIF had the best effects.For alcoholic metabolism in liver,the vitality of ADH was enhanced by velvet; EAV(1.0g,/kg、2.0g/kg) could enhanced the vitality of ADH(1.42±0.06U/mg、1.52±0.03U/mg),their effects both surpassed velvet powder(1.11±0.04U/mg).Velvet could effectively inhibit liver weight increasing caused by alcohol;EAV(2.0g/kg) reduced the liver weight coefficient to 4.99±0.23(P＜0.01),have as good effects as BIF.
4.The main results obtained from studies on the repair effects of velvet for the immune liver damage by APAP are as follows:
For protecting the liver's damaged cell,velvet could reduce content of ALT、AST; effects of BIF and EAV(2.0g/kg) were better,that of velvet powder(ALT:37.17±2.20U/L、AST:50.83±5.92U/L)was the worst.For enhancing the function of protein synthesis and reserve,the levels of TP、ALB were increased;the effects of BIF(38.35±1.31 g/L、27.61±0.65 g/L) was the best,and surpassed EAV;velvet powder was the worst.For adjusting the ability of liver with TBil ingested、combined and excreted,the level of TBil was increased in all groups(P＜0.01);the effects of BIF(7.85±0.51μmol/L) were the best,and surpassed EAV(2.0g/kg).For fatty metabolism in liver,TG's level was reduced obviously with velvet;EAV(2.0g/kg) could reduce the content of TG from 1.23±0.07mmo/L to 0.87±0.03mmo/L(P＜0.01),the effects were worse than BIF.For inhibiting lipid per-oxidation,the effects of heightening the vitality of SOD by velvet powder and EAV(1.0g/kg) were better,it was enhanced to 75.67±1.63U/mgprot and 75.57±1.88U/mgprot;the remedial effects of BIF were the best,and it was better than EAV(1.0g/kg) for reducing the level of MDA、NO.Velvet could obviously inhibit liver weight increasing(P＜0.01) caused by the immune liver damage;the effects of BIF(5.61±0.11)were the best,and EAV(2.0g/kg) was worse,the effects of velvet powder were the worst.
目前研究已经揭示鹿茸对肝损伤确有一定的修复作用,但对其抗肝损伤的具体作用及作用机理尚不十分清楚。本研究以小鼠为实验对象,利用CCl_4、APAP、56°白酒以及BCG+LPS几种毒物制造化学性、药物性、酒精性和免疫性四种不同类型的急性肝损伤模型,通过监测血清中ALT、AST、TP、ALB、TBil、TG的浓度和肝组织匀浆中MDA、SOD、NO、ADH的含量,来研究以马鹿茸为原料制备的鹿茸粉和鹿茸醇提物对不同类型肝损伤的修复作用及相关机理,旨在从肝细胞损伤、肝脏合成贮备功能、分泌排泄功能、脂代谢功能及脂质过氧化几个方面阐明鹿茸对肝脏的保护作用及部分作用机理,为充分开发鹿茸新的药用价值,研制鹿茸抗肝损伤的新型医疗保健药物提供生化药理学基础。
1.鹿茸对CCl_4所致化学性肝损伤修复作用的研究结果表明:
对肝细胞损伤的保护作用方面,鹿茸醇提物1.0g/kg、2.0g/kg均可以明显降低ALT、AST的含量(P＜0.01),其中醇提物2.0g/kg将ALT由204.08±72.00U/L降至55.21±7.93U/L,AST由234.77±7.71U/L降至80.57±10.80U/L,其降酶作用与联苯双酯(71.25±14.06、79.83±11.02U/L)相当。在提高肝脏蛋白合成储备功能方面,鹿茸醇提物1.0g/kg、2.0g/kg均能明显提高血清TP(56.94±5.96、59.90±3.89g/L)及ALB(31.80±0.92、31.30±0.72g/L)含量(P＜0.01),作用效果优于联苯双酯(37.94±5.80、29.18±2.78g/L),而鹿茸粉效果不显著。对肝脏排泄分泌功能的改善方面,鹿茸醇提物2.0g/kg能将血清TBil明显降低至6.35±0.22μmol/L(P＜0.01),效果与联苯双酯(6.33±0.29μmol/L)相当,而鹿茸醇提物1.0g/kg稍差(P＜0.05)。改善肝脏脂代谢功能方面,各治疗组均能降低血清TG含量,其中鹿茸醇提物2.0g/kg可将TG由1.03±0.09mmol/L降至0.70±0.12mmol/L,作用效果明显(P＜0.05)且与联苯双酯(0.87±0.06mmol/L)相当。在对抗肝脏自由基的脂质过氧化方面,鹿茸醇提物能显著提高SOD活力、降低MDA和NO水平(P＜0.01),鹿茸醇提物2.0g/kg作用效果稍好,可将SOD活力提高至78.75±0.56U/mgprot,MDA和NO含量降低至0.93±0.07nmol/mg和40.82±3.73umol/L,而鹿茸粉效果较差。此外,鹿茸能显著降低肝损伤小鼠的肝重系数(P＜0.01),醇提物1.0g/kg组肝重系数为5.01±0.12,其作用效果较2.0g/kg组(5.16±0.07)稍好,但差异不明显。
2.鹿茸对APAP所致药物性肝损伤修复作用的研究结果表明:
对受损肝细胞的保护作用方面,鹿茸醇提物2.0g/kg将ALT、AST分别降至38.38±2.19U/L、36.75±0.92U/L,作用效果优于1.0g/kg(41.67±11.56U/L、56.67±8.09U/L)。在蛋白合成储备功能方面,各治疗组TP含量均有小幅升高,其中醇提物1.0g/kg组TP升高至38.17±0.76g/L,鹿茸粉组升高至27.17±0.61g/L,两组效果均显著(P＜0.05),而ALB含量升高幅度较大,醇提物2.0g/kg治疗效果最好(P＜0.01),其ALB含量高达29.86±1.00g/L。在改善肝脏的胆汁瘀滞程度方面,各治疗组TBil含量均明显降低(P＜0.01),其中鹿茸醇提物2.0g/kg可将TBil降低至8.59±0.27μmol/L,作用效果优于醇提物1.0g/kg,但均低于联苯双酯(8.27±0.38μmol/L)。对脂代谢功能的调节方面,各治疗组TG含量都有大幅度的降低(P＜0.01),其中鹿茸醇提物2.0g/kg的疗效最好,其TG由1.68±0.05mmol/L降至0.86±0.03mmol/L,低于联苯双酯(0.61±0.02mmol/L)。鹿茸各治疗组均能在一定程度上提高SOD活力,降低NO和MDA水平,抑制APAP所致受损肝脏的脂质过氧化反应,但均未达到联苯双酯组中SOD(77.56±2.18U/mgprot)、MDA(0.77±0.06nmol/mg)和NO(45.24±4.39umol/L)水平。鹿茸还能能显著降低APAP急性肝损伤小鼠的肝重系数,其中醇提物2.0g/kg组与模型组相比差异极显著(P＜0.01),将肝重系数由6.52±0.23降至5.64±0.11,作用效果较1.0g/kg的明显。
3.鹿茸对酒精性肝损伤修复作用的研究结果表明:
对减轻肝细胞的损伤程度方面,各组ALT、AST均有不同程度的降低,其中鹿茸醇提物2.0g/kg对AST的降低效果极显著(P＜0.01),可将AST由56.00±2.31U/L降至36.42±1.45U/L,结合ALT和AST综合判断,鹿茸醇提物2.0g/kg效果最佳。对改善肝脏的合成储备功能方面研究发现,鹿茸对促进TP的合成作用不显著,而能显著增加肝脏对ALB的合成功能(P＜0.01),鹿茸醇提物2.0g/kg作用效果较好,能将其提高至28.71±1.12g/L,仅次于联苯双酯的29.15±0.95g/L。在肝脏对TBil的摄取、结合和排泄能力方面,鹿茸缓解急性酒精肝损伤小鼠肝脏胆汁瘀滞的程度,给药后各组TBil含量均大幅降低(P＜0.01),其中鹿茸醇提物1.0g/kg作用效果最好,使TBil达到10.99±1.55μmol/L,仅次于联苯双酯(9.46±0.11μmol/L)。鹿茸能有效抑制脂肪变性,调整脂代谢功能,鹿茸醇提物1.0g/kg组和鹿茸粉组可将TG降低至0.80±0.07mmo/L和0.94±0.02mmol/L,作用效果较差,而鹿茸醇提物2.0g/kg能将TG降低至0.65±0.28mmol/L,作用效果极显著(P＜0.01),且与联苯双酯(0.61±0.07mmol/L)相当。在抗急性酒精肝损伤脂质过氧化方面,鹿茸粉作用效果低于鹿茸醇提物,其中醇提物2.0g/kg效果最好,可将SOD活性提高至73.20±0.60U/mgprot,MDA和NO含量降低至1.05±0.07nmol/mg和50.00±3.19umol/L,但均低于联苯双酯。在肝脏对酒精的代谢能力方面,鹿茸能明显增加肝脏ADH活性,与模型组相比,鹿茸粉可使ADH活性由0.93±0.03U/mg提高至1.11±0.04U/mg(P＜0.05),其作用效果明显低于鹿茸醇提物1.0g/kg组的1.42±0.06U/mg和2.0g/kg组的1.52±0.03U/mg(P＜0.01)。此外,鹿茸能有效抑制大量饮酒造成的肝脏重量的增加,鹿茸醇提物2.0g/kg作用效果最好(P＜0.01),将肝重系数降至4.99±0.23,作用与联苯双酯相当。
4.鹿茸对BCG和LPS联合所致免疫性肝损伤修复作用的研究结果表明:
对肝细胞损伤的保护作用方面,鹿茸给药后ALT、AST均不同程度降低,鹿茸醇提物2.0g/kg可将ALT、AST分别由43.79±1.51U/L、53.50±1.72U/L降至33.33±2.78U/L、39.50±0.93U/L,其对于免疫性肝损伤的保护作用较1.0g/kg稍好而与联苯双酯相当,鹿茸粉(37.17±2.20U/L、50.83±5.92U/L)作用最差。在促进肝脏蛋白质的合成代谢功能方面,各组TP和ALB均有不同程度的提高,鹿茸醇提物效果高于鹿茸粉,其中醇提物2.0g/kg效果较好,可将TP、ALB分别提高至36.81±0.55g/L、26.62±0.54g/L,但低于联苯双酯(38.35±1.31g/L、27.61±0.65 g/L)。在改善摄取、转化和排泄TBil的能力方面,给药后各组TBil含量均极显著降低(P＜0.01),鹿茸醇提物2.0g/kg将TBil由17.42±0.74μmol/L降低至8.82±0.20μmol/L,作用效果优于其它组,仅次于联苯双酯(7.85±0.51μmol/L)。在调节脂代谢功能方面,各组TG含量在用药后均明显降低,鹿茸醇提物2.0g/kg降低幅度最大(P＜0.01),由1.23±0.07mmo/L降至0.87±0.03mmo/L,效果较联苯双酯(0.79±0.03mmo/L)稍差。对抑制脂质过氧化方面,鹿茸粉和鹿茸醇提物1.0g/kg提高SOD活力的效果较好,可使SOD值达到75.67±1.63U/mgprot和75.57±1.88U/mgprot,鹿茸醇提物降低MDA的效果优于鹿茸粉,其中醇提物2.0g/kg(1.22±0.07nmol/mg)效果略高于1.0g/kg(1.39±0.10 nmol/mg),而NO的降低效果以鹿茸醇提物1.0g/kg效果最为理想,由61.22±5.14umol/L降低至40.82±6.56umol/L,根据MDA、SOD和NO综合分析,鹿茸醇提物1.0g/kg抗脂质过氧化反应的效果较好,但较联苯双酯稍差。此外,鹿茸能抑制免疫性肝损伤造成的肝脏重量的增加,鹿茸粉效果最差,仅由6.22±0.10降至5.97±0.07,鹿茸醇提物2.0g/kg效果较好(P＜0.01),可将达5.74±0.10,但效果低于联苯双酯(5.61±0.11)。
The acute liver damage was a kind of common pathological changes of various liver diseases.A characteristic feature of the pathology was hepatocyte degeneration,necrosis, even apoptosis.Its long-term existence always leaded to hepatic fibrosis,cirrhosis and hepatoma.Therefore,preventing and curing liver damage were the key points of treating clinical liver diseases.Controlling the liver damage in time was particularly important to cure the liver diseases.Velvet has extensive pharmacological action and medical care function.In modern medical practice,the medicines with velvet as its main raw materials gained good effects on treating many diseases.But velvet wasn't used to treat the liver disease.If velvet could be applied to the treatment of liver diseases and the health care,that it could not only resolve a difficult medical problem,but also bring huge economic benefit and the social effect.Some studies showed that velvet had certain repair action for the liver damage,but the action mechanism was still not very clear.
In this study,we dealt the rats with CCl_4、APAP、alcohol and BCG+LPS,established the model of acute liver damage,such as chemical,medicamentosa and immune liver damage.By measuring the content of ALT、AST、TP、ALB、TBil、TG in serum and MDA、SOD、NO、ADH in liver homogenate,expounded the effects and mechanism of velvet powder and the EAV(extract by alcohol from velvet) for the liver damage,finally it could build the foundation of biochemistry and pharmacology for anti-liver damage of velvet.
1.The main results obtained from studies on the repair effects of velvet for the chemical liver damage are as follows:
In terms of protecting the liver cell damage,the EAV(1.0g/kg and 2.0g/kg) could reduce the content of ALT and AST in serum(P＜0.01) obviously.The rats were treated with EAV(2.0g/kg),then the content of ALT was reduced from 204.08±72.00U/L to 55.21±7.93U/L,and the content of AST was reduced from 234.77±7.71U/L to 80.57±10.80U/L;the same effects existed between BIF(71.25±14.06、79.83±11.02U/L ) and EAV(2.0g/kg).In terms of enhancing the function of protein synthesis and reserve, EAV(1.0g/kg and 2.0g/kg) could increase the content of TP(56.94±5.96、59.90±3.89g/L) and ALB(31.80±0.92、31.30±0.72g/L) in serum obviously(P＜0.01),the protective effects was superior to the BIF(37.94±5.80、29.18±2.78g/L);but the effects of velvet powder was not prominent.In terms of improving the liver excretory ability,EAV(2.0g/kg) could reduce the content of TBil(6.35±0.22μmol/L) obviously(P＜0.01) obviously,its effects were as good as BIF(6.33±0.29μmol/L);but the EAV(1.0g/kg) was a little worse(P＜0.05).In terms of improving the liver fat metabolism,the content of TG in each treatment group were reduced;the EAV(2.0g/kg) could reduce the content of TG form 1.03±0.09mmol/L to 0.70±0.12mmol/L,the same effects occurred between BIF(0.87±0.06mmol/L) and EAV(2.0g/kg).For reducing lipid peroxidation of free radicals in liver,the EAV could enhance the vitality of SOD obviously,and reduce the level of MDA and NO(P＜0.01);the EAV(2.0g/kg) could increase the content of SOD(78.75±0.56U/mgprot),and reduce the content of MDA(0.93±0.07nmol/mg) and NO(40.82±3.73umol/L);but the effects of velvet powder was bad.Besides these,velvet could reduce the rat's liver weight coefficient obviously(P＜0.01),but the difference was not significant in each group.
2.The main results obtained from studies on the repair effects of velvet for the medicamentosa liver damage by APAP are as follows:
For protecting the liver's damaged cell,EAV(2.0g/kg) could reduce the content of ALT(38.38±2.19U/L) and AST(36.75±0.92U/L),its effects were better than that of EAV(1.0g/kg).For enhancing the function of protein synthesis and reserve,the content of TP in each treatment group had a small rise;the difference between the effects(38.17±0.76g/L) of EAV(1.0g/kg)and that(27.17±0.61g/L) of velvet powder was significant;the content of ALB had a big rise,EAV(2.0g/kg) remarkable enhanced ALB's content(29.86±1.00g/L),its effects were the best(P＜0.01).For improving cholestasis of liver,the content of TBil reduced obviously,the effects of BIF(8.27±0.38μmol/L) were better than that(8.59±0.27μmol/L) of EAV(2.0g/kg).For adjusting lipid metabolism,the level of TG in each treatment group was reduced a lot(P＜0.01).EAV(2.0g/kg) reduced TG's level from 1.68±0.05mmol/L to 0.86±0.03mmol/L,the level was lower than BIF(0.61±0.02mmol/L).Velvet could enhance the vitality of SOD in each treatment group, and reduce the level of NO and MDA;inhibit the lipid per-oxidization of damaged liver of rats dealt with APAP,but their effects were worse than BIF.Velvet could reduce the rat's liver weight coefficient obviously,EAV(2.0g/kg) was the better than EAV(1.0g/kg),it could reduce the liver weight coefficient from 6.52±0.23 to 5.64±0.11.
3.The main results obtained from studies on the repair effects of velvet for the alcoholic liver damage are as follows:
For alleviating the liver's damaged cell,the levels of ALT、AST all reduced, EAV(2.0g/kg) reduced the content of AST from 56.00±2.31U/L to 36.42±1.45U/L very significantly,its effects were the best.For enhancing protein synthesis and reserve of liver, velvet could not improved TP synthesis remarkably,but could improved ALB synthesis evidently(P＜0.01);but the remedial ability of EAV(2.0g/kg) was worse than BIF(29.15±0.95g/L).For adjusting the ability of liver with TBil ingested、combined and excreted,velvet could alleviate cholestasis of liver,the content of TBil was reduced in each treatment group obviously(P＜0.01) after dealt with velvet;the effects of BIF(9.46±0.11μmol/L) were better than EAV(1.0g/kg),was the best.Velvet could inhibit fatty degeneration and adjust its metabolism;the effects were good by BIF(0.61±0.07mmol/L) and EAV(2.0g/kg),the effects surpassed EAV(1.0g/kg) and velvet powder(0.94±0.02mmol/L) in remedial ability.For acuted lipid per-oxidation by alcohol in damaged liver,remedial ability of EAV(1.0g/kg、2.0g/kg) was better than velvet powder,EAV(2.0g/kg) could adjust the vitality of SOD(73.20±0.60U/mgprot),and reduce the level of MDA(1.05±0.07nmol/mg) and NO(50.00±3.19umol/L);but BIF had the best effects.For alcoholic metabolism in liver,the vitality of ADH was enhanced by velvet; EAV(1.0g,/kg、2.0g/kg) could enhanced the vitality of ADH(1.42±0.06U/mg、1.52±0.03U/mg),their effects both surpassed velvet powder(1.11±0.04U/mg).Velvet could effectively inhibit liver weight increasing caused by alcohol;EAV(2.0g/kg) reduced the liver weight coefficient to 4.99±0.23(P＜0.01),have as good effects as BIF.
4.The main results obtained from studies on the repair effects of velvet for the immune liver damage by APAP are as follows:
For protecting the liver's damaged cell,velvet could reduce content of ALT、AST; effects of BIF and EAV(2.0g/kg) were better,that of velvet powder(ALT:37.17±2.20U/L、AST:50.83±5.92U/L)was the worst.For enhancing the function of protein synthesis and reserve,the levels of TP、ALB were increased;the effects of BIF(38.35±1.31 g/L、27.61±0.65 g/L) was the best,and surpassed EAV;velvet powder was the worst.For adjusting the ability of liver with TBil ingested、combined and excreted,the level of TBil was increased in all groups(P＜0.01);the effects of BIF(7.85±0.51μmol/L) were the best,and surpassed EAV(2.0g/kg).For fatty metabolism in liver,TG's level was reduced obviously with velvet;EAV(2.0g/kg) could reduce the content of TG from 1.23±0.07mmo/L to 0.87±0.03mmo/L(P＜0.01),the effects were worse than BIF.For inhibiting lipid per-oxidation,the effects of heightening the vitality of SOD by velvet powder and EAV(1.0g/kg) were better,it was enhanced to 75.67±1.63U/mgprot and 75.57±1.88U/mgprot;the remedial effects of BIF were the best,and it was better than EAV(1.0g/kg) for reducing the level of MDA、NO.Velvet could obviously inhibit liver weight increasing(P＜0.01) caused by the immune liver damage;the effects of BIF(5.61±0.11)were the best,and EAV(2.0g/kg) was worse,the effects of velvet powder were the worst.
引文
[1]张辉.鹿茸生产技术.北京:中国农业出版社,2004:1
[2]李继海.梅花鹿茸活性成分提取分离、功能评价及功能食品研究(博士学位论文).北京:中国农业大学,2005:1
[3]李和平.中国茸鹿品种(品系)的生态种特征.东北林业大学学报.2001.29(5):52-57
[4]韩盛兰.鹿养殖与产品加工.北京:科学技术文献出版社,2004:4-10
[5]秦荣前.中国梅花鹿.北京:中国农业出版社,1994:175
[6]柴中元,施仁潮.鹿茸.杭州:浙江科学技术出版社,2003:11,19-20
[7]J.M.Suttie,C.,Li,G..A.,Bubenik,H.J.,Rolf.Studies of antler growth:A review of the literature.Plenary lecture,1998:375-382
[8]赵世臻,沈广.中国养鹿大成.北京:中国农业出版社,1998:210-214
[9]Bernhard,K.,Brubacher,G.,Hediger,H.,et al.The chemical composition and structure of deer antlers.Experientia,1953,9:138-140
[10]金顺丹,郑敏芝.鹿茸有效成分的研究(第一报).特产科学实验,1979,(4):24-28
[11]卞祖福,袁丽华,段传凤.三种驯鹿茸与梅花鹿茸的化学成分比较.特产科学实验,1985,4:49-52
[12]张经华,杨若明,张林源等.麋鹿梅花鹿和马鹿鹿茸中微量元素的分析测定.微量元素与健康研究,2000,17(4):39-40
[13]Silaev,A.B.,Katrukha,G.S.,Shampanova,O.M.,et al.Amino acid and mineral composition of antlers and pantocrine.Sbornik nauchnykh rabot nauchno-lssledovatel' skoi laboratotii pantovogo ollenevodstva,1969,2:29-32
[14]屈立新,唐越,王向东等.鹿茸精的心肌保护作用机理.中华实验外科杂志,1999,16(1):66-67
[15]谷天祥.心肌缺血再灌注Na~+-K~+ATPase活性变化及鹿茸精的保护作用.中国医科大学学报,1999,28(4):282-285
[16]孙晓波,周重楚.鹿茸精强壮作用的研究.中药药理与临床,1987,3:11-13
[17]张永和,黄晓巍,孙靖辉等.鹿茸醇提物对心肌梗死模型大鼠心肌损伤的保护作用及对血浆内皮素含量的影响.中国中药药信息杂志,2007,14(1):40-41
[18]潘麟士译.鹿茸的作用机理.福建医药杂志,1980,2(2):64
[19]徐惠波.鹿茸神经节甙酯对小鼠学习记忆功能的影响.中国药理学通报,1991,7(5):385-388
[20]陈晓光,杨明,王本祥等.人工培养鹿茸细胞的药理作用.中药药理与临床,1990,6 (1):30-32
[21]王岩,金淑莉,陈晓光.鹿茸胶囊抗惊厥和镇静作用的实验研究.长春中医学院学报,2003,19(2):31-32
[22]李立军,路来金,陈雷等.鹿茸多肽促进大鼠坐骨神经再生的实验研究.辽宁中医杂志,2004,31(4):343-344
[23]陈东,孟晓婷,刘佳梅等.鹿茸多肽对胎大鼠脑神经干细胞体外诱导分化的实验研究.解剖学报,2004,35(3):240-243
[24]孙晓波,周重楚.鹿茸精对机体免疫功能的影响.中成药研究,1986,2:24-25
[25]Wang BX,Zhao XH,Qi SB,et al.Effects of repeated administration of deer antler extract on biochemical changes related to aging in senescence acceleratedmice.Chem Pharm Bull.1988,36(7):2587-2592
[26]高云端,孙尚奎,李柏岩等.鹿茸精注射液性激素样作用的实验研究.中药药理与临床,1990,2:23-24
[27]田育璋,贺菊香,王丰梅等.鹿茸对大鼠睾丸影响的形态计量.青海医学院学报,1997,18(3):154-155
[28]杨若明,张经华,周素红等.麋鹿茸中的性激素对大鼠和小鼠生殖系统的影响.解剖学报,2001,32(2):180-182
[29]洪文,李建强,王照浩等.针灸治疗肾阳虚型男性不育症30例疗效观察.新中医,2002,34(5):39-40
[30]王家辉,张红梅,房景奎等.参茸配伍对腺嘌呤应用法雄性大鼠肾阳虚动物模型性腺损伤调整作用的实验研究.中华男科学,2004,10(4):315-319
[31]王本祥,刘爱晶,程秀娟.鹿茸多糖抗溃疡作用.药学学报,1985,5:321-325
[32]翁梁,周秋丽,王丽娟等.鹿茸多肽促进皮肤和成纤维细胞增殖及皮肤创伤愈合.药学学报,2001,36(11):817
[33]王岩,金淑莉,陈晓光.鹿茸胶囊抗炎镇痛作用的研究.吉林中医药,2003,23(6):48
[34]赵咏梅,陈晓光.鹿茸口服液抗炎、镇痛、免疫增强作用的实验研究.中国中医药科技,2005,12(2):128
[35]Allen Marion,Oberle Kathleen,Grace Michael,et al.Elk velvet antler in rheumatoid arthritis:phase Ⅱ trial.Biological research for nursing,2000,3(3):111-118
[36]Yeon-Kye Kim,Kyung-Sook Kim,Kang-Hyun Chung,et al.Inhibitory effects of deer antleraqua-acupuncture,the pilose antler of Cervus Korean Temminck var.mantchuricus Swinhoe,on type Ⅱ collagen-inducedarthritis in rats.International Immunopharmacology, 2003,3(7):1001-1010
[37]丁钰熊.鹿茸精注射液治疗血虚动物的实验研究.中成药,1991,1:27
[38]姚克霓.补血生髓胶囊药理作用的研究.基层中药杂志,1996,10(3):35-36
[39]陈莉萍,彭源贵,谢绍明等.参茸白凤膏的药理作用研究.中药药理与临床,1997,13(6):12-14
[40]潘勤.参桂鹿茸丸治疗慢性原发性低血压综合症35例.湖南中医药导报,1996,2(5):17
[41]陈书明,聂向庭,刘桂林等.鹿茸醇提物对白细胞减少动物模型影响初探.实验动物科学与管理,1999,16(4):32-33
[42]陈书明,聂向庭.鹿茸醇提物对用环磷酰胺处理的小白鼠红细胞免疫功能的影响.经济动物学报,2000,4(1):23-25
[43]丁长海,吴成义,魏伟等.鹿茸液的药理作用研究.安徽医科大学学报,1995,30(1):4-6
[44]梁贞爱,宋成岩,金忠吉.复方鹿茸煎剂对小鼠耐缺氧能力和抗疲劳作用的影响.中国医药科技,2002,9(3):152
[45]Shin,Kuk Hyun.,Yun-Choi,Hye Sook.,Lim,Soon Sung.,et al.Immuno-stimulating,anti-stress and anti-thrombotic effects of unossified velvet antlers.Natural product scienences,1999,5(1):54-59
[46]刘正才.从现代免疫学角度探讨中医药的抗衰老作用.浙江中医杂志,1981,16(6):272-275
[47]金光湖.鹿茸对氨甲喋吟引发的免疫功能低下的影响.黑龙江中医药,1993,2:40-42
f48]李志如.鹿角胶治疗急性乳腺炎的临床观察.中医杂志,1961,12(6):24-26
[49]连玉树.鹿茸的药理与临床.中医药学报,1988,6:41-46
[50]张廷良.张连仁治疗虚寒型脉管炎的经验.上海中医药杂志,1989,1:12-13
[51]唐巍然,于晓红,闻杰等.鹿茸多糖对免疫功能低下模型小鼠细胞免疫功能的影响.中国中医药科技,2000,7(4):234
[52]陈书明,聂向庭.鹿茸醇提物对白细胞减少小鼠模型腹腔吞噬细胞吞噬功能的影响.山西中医学院学报,2000,1(1):4-5
[53]丁克祥,陈华东.鹿茸的抗衰老作用及其机理.中国老年学杂志,1994,14(2):108-110
[54]Chen X.,Jia Y.,Wang B.Inhibitory effects of the extract of pilose antler on monoamine oxidase in aged mice.Zhongguo Zhongyao Zazhi,1992,17(2):107-110
[55]衣欣,李健民,袁慎萸等.肾阳虚模型大鼠与衰老的关系及鹿茸的作用.中药药理与临床,1997,13(5):34-35
[56]陈书明,聂向庭.鹿茸醇提物抗氧化作用的实验研究.实验动物科学与管理,2000,17(1):22-24
[57]葛迎春,李晨燕,任慧君等.鹿茸提取物和人参皂甙对衰老细胞的琥珀酸脱氢酶和多糖含量的影响.特产研究,2001,2:5-7
[58]王本祥,刘爱晶,程秀娟等.鹿茸多糖抗溃疡作用.药学学报,1985,5:321-325
[59]霍玉书,霍虹.鹿茸神经生长因子活性及促分化作用的研究.中药新药与临床药理,1997,8(2):79
[60]范玉林,邢增涛,卫功庆.鹿茸蛋白的提取分离及其抗肿瘤活性.经济动物学报,1998,2(1):27
[61]Kim,Dong-Hyun.,Park,Hae-Young.,Kim,Nam-Jae.,et al.Protective effect of antler in experimental colon carcinogenesis.Natural product sciences,1999,5(1):48-53
[62]Wang BX,Zhao XH,Qi SB,et al.Stimulating effect of deer antler extract on protein synthesis in senescence-accelerated mice in vivo.Inbid,1988,36(7):2593-2598
[63]Wang BX.Influence of the active compounds isolated from pilose antler on syntheses of protein and RNA in mouse liver.Yao Xue Xue Bao,1990,25(5):321-325
[64]陈书明,聂向庭,刘广金.鹿茸醇提物对环磷酰胺所致小鼠遗传物质损伤的影响.山西医科大学学报,2000,31(1):24-25
[65]刘秀梅,祁雪,陈晓光.鹿茸口服液降脂作用的研究.中药药理与临床,2003,19(6):38-39
[66]祁雪,刘秀梅,陈晓光.鹿茸口服液对小鼠实验性肝损伤的保护作用.中药药理与临床,2004,20(1):42-43
[67]余明泽,宋述辉,周毓.鹿茸对大鼠酒精性肝损害的拮抗作用.中国公共卫生学报,1996,15(3):172-173
[68]Kirn HS.Inhibitory effects of velvet antler water extract on morphine- induced conditioned place preference and DA receptor supersensitivety in mice.Ethnopharmacol,1999,66(1):25-31
[69]曹译.鹿茸对去卵巢大鼠所致骨质疏松症治疗作用的研究及鹿茸中硫酸软骨素的提取(硕士学位论文).长春:吉林大学,2005:49
[70]顾祖维.现代毒理学概论.北京:化学工业出版社,2005:157
[71]Shah H,Hartman SP,Weinhouse S.Formation of carbonyl chloride in carbon tetrachloride metabolism by rat liver in vetro.Cancer Res,1979,39:3942-3947
[72]Berger ML,Bhatt H,Combes B,et al.CCl_4-induced toxicity in isolated hepatocytes.Hepatology,1986,6:36-45
[73]Castro GD,Diaz Gomez MI,Castro JA.DNA bases attack by reactive metabolites produced during carbon terachloride biotransformation and promotion of liver microsomal lipid peroxidation.Res Commun Mol Pathol Pharmacol,1997,95:253-258
[74]Arosio B,Santambrogio D,Gagliano N,et al.Glutathione pretreatment lessens the acute liver injury induced by carbon tetrachloride.Pharmacol Toxicol,1997,81:164-168
[75]唐望先,虞涤霞,但自力等.肝炎平对大鼠慢性肝损害胶原纤维作用的实验研究.胃肠病学和肝病杂志,1998,7:167-169
[76]刘建文.药理实验方法学.北京:化学工业出版社,2004:168
[77]王淳,刘礼意,吉兰.D-氨基半乳糖盐酸盐诱发的肝损伤模型.中草药,1980,11(6):262-264
[78]Bessems JG,Vermeulen NP.Paracetamol(acetaminophen)-induced toxicity:Molecular and Biochemical Mechanisms,Analogues and Protective Approaches.Crit Rev Toxicol,2001,31(1):55-138
[79]Wang T,Shankar K,Ronis M,et al.Potentiation of thioacetamide liver injury in diabetic rat is due to induced CYP2E1.J Pharm Exp Ther,2000,294(2):473
[80]Gujral JS,Knight TR,Farhood A,et al.Mode of Cell Death after Acetaminophen Overdose in Mice:Apoptosis or Oncotic Necrosis Toxicol.Sci,2002,67(2):322-328
[81]Macrides TA,Naylor LM,Kalafatis N,et al.Hepatoprotective effects of the shark bile salt 5 beta-scymnol on acetam inophen-induced liver damage in mice.Fundam Appl Toxicol,1996,33:31-37
[82]Liu GT.Present status of anti-hepatitis drugs and its perspective.In:Society office of China Association for sciences and technology.Research on prevention and therapy of viral hepatitis.Beijing:Chin Sci Tech Press,1991:337-341
[83]邱英锋,缪晓辉,蔡雄等.卡介苗加脂多糖建立的大鼠急性免疫性肝损伤模型的研究.西北国防医学杂志,2004,25(5):345
[84]Tiegs G,Hentschel J,Wendel A.T Cell-dependent experimental liver injury in mice inducible by Concanavalin A.Clin Invest,1992,90:196-203
[85]李绍旦,袁本利.ConA诱导肝细胞损伤机理及CsA对其损伤的影响.胃肠病学和肝病学杂志,2004,13(5):471-474
[86]Dawei C,Robert J,Zeytun A,et al.CD44-deficient Mice Exhibit Enhanced Hepatitis after Concanavalin a Infection:Evidence for Involvenment of CD44 in Activaion-induced Cell Death.J Immunol,2001,166(10):5889-5897
[87]黄健,楼雅卿.酒精和肝脏.中国药物依赖性杂志.2000,9(2):88-90
[88]王明春,吴承荣,姜英.酒精性肝病的研究进展.Chin J clini Hepatol,1998,14(3):142-144
[89]Plaa GL.Chlorinated methanol and liver injury:highlights of the past 50 years.Annu Rev Pharmacol Toxicol,2000,4040-4065
[90]杨光华.病理学(第5版).北京:人民卫生出版社,2001:14
[91]江正辉,王泰龄.酒精性肝病.北京:中国医药科技出版社,2001:100-107
[92]Tsukamoto H,Tower SJ,Ciofalo LM,et al.Ethanol induced liver fibrosis in rats fed high-fat diet.Hepatology,1986,6:814-822
[93]赵静波,王泰龄,张晶等.大鼠急性酒精性肝损伤模型分析.中日友好医院学报,1996,10(1):17-19
[94]童英,姚小曼,吴少平.乙醇诱发急性肝损伤生物标记物的探讨.中国食品卫生杂志,1999,11:12-14
[95]长尾由纪子,叶木荣,赖小平.实验性肝损伤模型建立的初步探讨.广西中医药,2006,29(3):47-49
[96]唐云安,刘玉清,王国钦.肝损伤动物模型研究进展.卫生毒理学杂志,2002,16(04):236-238
[97]Kaplowitz N.Mechanisms of liver cell injury.J Hepatol,2000,32(1Suppl):39-47
[98]Patel T,Gores GJ.Apoptosis and hepatobiliary disease.Hepatolgy,1995,21(6):1725-1741
[99]Recknagel RO,Glende EA Jr,Dolak JA,Waller RL.Mechanisms of carbon tetrachloride toxicity.Pharmacol Ther,1989,43(1):139-154
[100]王鸿利.实验诊断学,人民卫生出版社,2001:49
[101]詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报,2006,41(6):664-666
[102]罗文,杜芳腾,刘晶美.实验性大鼠肝损伤肝组织铜锌变化研究.江西医学院学报,1998,38(2):21-23
[103]李烨.双环醇对实验性肝损伤、肝纤维化的保护作用和保护机制的研究(博士学位论文).北京:中国协和医科大学中国医学科学院,2001:71-72,51
[104]陈诗书.医学生物化学.北京:科学出版社,2005,366-372,123-124
[105]唐丽英.血清总胆汁酸与胆红素在肝胆疾病中的相关关系探讨.南华大学学报,2002,30(3):296-297
[106]贺巾超.rhKD/APP的制备和对肝损伤保护的研究(博士学位论文).吉林大学,2006:83
[107]黄梅芳,朱龙庆.酒精性肝病发病机制的研究进展.医学新知杂志,2003,13(2):104
[108]Yamagchi Y,Okabe K,Matsumoto F,et al.Peroxynitrite formation during rat hepatic allograft rejection.Hepatology,1999,29:777
[109]Li J,Sun M,Hsn M.NO、SOD and NOS in injuried liver of fetus rat with intrauterine asphyxia.Shijie Huaren xiaohua Zazhi,2002,10(2):177-181
[110]赵铁建,钟振国,方卓等.白花丹水煎液对四氯化碳慢性肝损伤小鼠肝组织脂质过氧化的影响.广西医科大学学报,2006,23(5):725-726
[111]李宏涛,陈国民.D-氨基半乳糖研究的回顾和展望.肝脏,2004,9(3):209-210
[112]尹家乐,李心,张士侠等.白首乌C21甾体酯苷对小鼠急性四氯化碳肝损伤的保护作用.安徽医药,2007,11(3):198-200
[113]Jaeschke H,Gores GJ,Cederbaum AI,et al.Ycchanism of hepatotoxicity.Toxicol Sci,2002,65:166-176
[114]Chen J,Robinson NC,Schenker S,et al.Formation of 4-hydroxynonenal adducts with cytochrome C oxidase in rats following short-term ethanol intake.Hepatology,1999,29:1792-1798
[115]Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem,2000,275:2247-2250
[116]王宪龄,张丽萍,李连珍等.柴胡黄芩配伍不同提取部位对扑热息痛所致小鼠急性肝损伤的保护作用.中药药理与临床,2005,21(3):10-11
[117]Macrides TA,Naylor LM,Kalafatis N,et al.Hepatoprotective effects of the shark bile salt 5beta2scymnol on acetaminophen-induced liver damage in mice.Fundam Appl Toxicol,1996,33:31-37
[118]Hinson JA,Pike SL,Pumfrd NR,et al.Nitrotyrosine-protein adducts in hepatic centrilobular areas following toxic does of acetaminophen in mice.Chem Res Toxicol,1998,11:604-607
[119]王小丽,黄真,江丽霞等.黄花倒水莲提取物对小鼠实验性肝损伤的保护作用.时珍国医国药,2007,18(6):1320-1321
[120]刘春棋,卑占宇,李洪亮等.六月雪水提取物对小鼠实验性肝损伤的保护作用.赣南医学院学报,2006,26(6):824-825
[121]吴丽,魏伟.肝纤维化的动物模型及治疗药物研究.中国药理学通报,2004,20(5):481-485
[122]Potter W.Z.,Davis D.C.,Mitchell J.R.,et al.Acetaminophen-induced hepatic necrosis.Ⅲ.Cytochrome P450-mediated covalent binding in vitro.J Pharmacol Exp Ther,1973,187:203
[123]Critchley Julian,汪德清,丁保国等.黄芪总黄酮对扑热息痛所致肝损伤的防护机理探讨.中国中药杂志,2001,26(9):617-620
[124]刘钺,张朝明,郝玲等.血清总胆红素、甘氨胆酸、甲胎蛋白、糖类抗原19-9与胆汁瘀滞相关性评价.国际放射医学核医学杂志,2006,30(2):107-109
[125]吴建华,李波.舒肝灵对小鼠实验性肝损伤的防护作用.中西医结合肝病杂志,2000,10(3):27-28
[126]饶光宇,陈秀芬,张高等.迷迭香二萜酚提取物对几种肝损伤的保护作用.中草药,2001,32(5):434-436
[127]饶光宇,陈秀芬,于燕妮.茶多酚对小鼠实验性肝损伤的保护作用.中国中药杂志,2001,26(3):191-193
[128]汪德清,沈文梅,田亚平等.黄芪活性提取成分对膜脂质过氧化损伤的防护作用.中国中药杂志,1996,21(12):746-748
[129]Blazka ME,Wilmer JL,Holladay SD,et al.Role of proinflammatory cytokines in acetaminophen hepatotoxicity.Toxicol Appl Pharmacol,1995,133(1):43-45
[130]Kitamura K,Nakamoto Y,Akiyama M,et al.Pathogenic roles of tumor necrosis factor p55-mediated signals in dimethylnitrosamine-induced murine liver fibrosis.Lab Invest,2002,82(5):571-583
[131]Simpson KJ,Lukacs NW,McGregor AH,et al.Inhibition of turnout necrosis factor alpha does not prevent experimental paracetamol-induced hepatic necrosis.J.Pathol,2000,190(4):489-494
[132]Boess F,Bopst M,Althaus R,et al.Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-alpha gene Knockout mice.Hepatology,2001,27(4):1021-1029
[133]Gardner CR,Laskin JD,Dambach DM,et al.Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1 Potential role of inflammatory mediators.Toxicol Appl Pharmacol,2003,192(2):119-130
[134]巴吐尔.草棉花花瓣不同提取物的保肝及体外溶栓作用(硕士学位论文).乌鲁木齐:新疆医科大学学报,2005:11-13
[135]汪五三,宋建国.芝麻素保肝作用实验研究.中药药理与临床,2006,22(3):27-32
[136]Fang C,Lindros KO,Badger TM,et al.Zonated expression of cytokines in rat liver:effect of chronic ethanol and the cytochrome P450 2E1 inhibitor,chlormethiazole.Hepatology,1998,27:1304-1310
[137]Kukielka E,Dicker E,Cederbaum AI.Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment.Arch Biochem Biophys,1994,309(2):377-386
[138]Reinke LA,Moore DR,Mccay PB.Free radical formation in liver of rats treated acutely and chronically with alcohol.Alcohol Clin Exp Ther,1997,21(4):642-646
[139]Slomiany A,Piotrowski E,Grabska M,et al.Chronic ethanol-initiated apoptosis in hepatocytes is induced by changes in membrane biogenesis and intracellular transport.Alcohol Clin Exp Ther,1999,23(2):334-343
[140]倪力强.柴枳合剂治疗慢性酒精性肝损伤大鼠的实验研究(博士学位论文).沈阳:辽宁中医学院,2001:9-10
[141]叶永安,田德禄.慢肝消对大鼠酒精性肝损伤血清生化的影响.北京中医药大学学报,1999,22(6):31-32
[142]赵初环,卢中秋,李惠萍等.大鼠酒精性肝病模型的建立.浙江临床医学,2007,9(4):435-436
[143]王杰,姚凤云,杨伟鹏等.肝加欣片治疗酒精性肝病的实验研究.中国实验方剂学杂志,2006,12(8):39-40
[144]关光玉,曾家慧,张术斌等.酒精性脂肪肝小鼠模型的建立.宁夏医学杂志,2007,29(11):971-973
[145]曹阳.门冬氨酸鸟氨酸治疗酒精性肝病的临床疗效评价.实用肝脏病杂志,2007,10(3):194-195
[146]杜施霖,迟宝荣.龙牙葱木皂苷对大鼠酒精性肝病的防治作用.吉林大学学报,2005,31(1):64-67
[147]Niemela O,Parkkila S,Britton RS,et al.Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.J-Lab-Clin-Med,1999,133(5):451-460
[148]李颖.阿魏酸钠和当归醇沉物对免疫性肝损伤的干预作用.中草药,2000,31(4):274-276
[149]陈道荣,王丕龙.一氧化氮与酒精性肝病.胃肠病学和肝病学杂志,2003,12(4):392-394
[150]古赛.枸杞多糖防治大鼠酒精性脂肪肝的实验研究(博士学位论文).重庆:重庆医科大学,2007:28-29
[151]Oneta CM,Simanowski UA.First pass metabolism of ethanol is strikingly influenced by the speed of gastric empty.Gut,1996,43(5):612-619
[152]潘年松,黄勋,王毅等.护肝灵对实验大鼠酒精性脂肪肝的影响与机制探讨.陕西中医,2007,28(9):1265-1268
[153]毕业东,郭富成,张德祥.葛柏解酒液防治小鼠急性酒精中毒作用机理.实验研究,2005,17(5):50-51
[154]杨牧祥,于文涛,胡金宽等.酒速愈对急性酒精中毒小鼠解酒作用及酒精代谢的影响.中外健康文摘(医药月刊),2007,4(3):37-39
[155]Wang GS,Liu GT.Role of nitric oxide in immunological liver damage in mice.Biochem Pharmacol,1995,49(9):1277-1281
[156]黄玲.急性肝损伤和免疫性肝损伤动物模型研究述评.广州中医药大学学报,1998,15:67-69
[157]Hishinuma I,Nagakawa J,Hirots K,et al.Involvement of turmr necrosis factor in development of hepatic injury ingalac-to-samine-sensitized mice.Hepatology,1990,12:1187
[158]肖刚,王勤.罗汉果甜苷对小鼠实验性肝损伤保护作用的研究.中国药房,2008,19(3):163-165
[159]徐强,李庆云,吕凤娟,桑希生.牡蛎汤对免疫性肝损伤小鼠血清ALT、AST和肝组织TNF-a的影响.中国中医基础医学杂志,2008,14(2):104-105
[160]毛爱红,张昱,赵祁等.秃疮花提取物对小鼠免疫性肝损伤的保护作用.中国药理学通报,2004,20(8):940-943
[161]张慧娜,李诚秀,黄能慧等.汉丹肝乐对免疫性肝纤维化的预防作用.贵州医药,2001,25(5):415-417
[162]王天然,曾祥元,马布仁.硬肝复康对小鼠免疫性肝损伤的作用.成都中医药大学学报,2002,25(2):18-20
[163]万丽,万兴旺,胡晋红.绞股蓝总皂苷对免疫性肝纤维化大鼠肝功能和肝纤维化的影响.第二军医大学学报,2003,24(12):1319-1321
[164]洪素兰,杨敏,梁鹤,邵雷.肝舒乐片抗大鼠免疫性肝纤维化作用机制的实验研究. 光明中医,2005,20(5):45-47
[165]王明宇,林志彬.灵芝三萜类成分在体内外对小鼠免疫性肝损伤的影响.中国药学杂志,2000,35(12):808-811
[166]Cross CE.Oxygen RADecals and human disease.Ame inter Med,1987,107(4):526
[167]林志椿,聂松青.细胞膜的流动性.生理科学进展,1985,16(1):82-89
[168]Lwao K,Soichivo,Hajime H,et al.Increased intric Oxise Synthase activityas cause of mitochondrial dysfunction in rat hepatocytes.Hepatotogy,1996,24:1185
[169]Debra L,Marina R,Diane E,et al.Hipatic nitric oxide production following acute endotoxemia in rats is mediated by increased indue ible nitric oxide syt=nthas geneexpression.Hepatology,1995,22(1):223
[170]Yabuki M,Inai Y,Yoshika T,et al.Oxygen-dependent fragmentation of cellular DNA by nitric oxide.Free Radic Res,1997,26:245
[171]商玉萍,方士英,葛金芳等.虫草多糖对小鼠免疫性肝损伤的保护作用.华西药学杂志,2007,22(6):654-655
[172]胡成穆,姜辉,刘洪峰等.金银花总黄酮对小鼠免疫性肝损伤的保护作用.中药药理与临床,2007,23(5):85-88
[173]桑希生,李庆云,徐强.牡蛎汤对免疫性肝损伤小鼠肝组织NO、IL-2和TNF-a的影响.中医药信息,2007,24(5):68-69
[2]李继海.梅花鹿茸活性成分提取分离、功能评价及功能食品研究(博士学位论文).北京:中国农业大学,2005:1
[3]李和平.中国茸鹿品种(品系)的生态种特征.东北林业大学学报.2001.29(5):52-57
[4]韩盛兰.鹿养殖与产品加工.北京:科学技术文献出版社,2004:4-10
[5]秦荣前.中国梅花鹿.北京:中国农业出版社,1994:175
[6]柴中元,施仁潮.鹿茸.杭州:浙江科学技术出版社,2003:11,19-20
[7]J.M.Suttie,C.,Li,G..A.,Bubenik,H.J.,Rolf.Studies of antler growth:A review of the literature.Plenary lecture,1998:375-382
[8]赵世臻,沈广.中国养鹿大成.北京:中国农业出版社,1998:210-214
[9]Bernhard,K.,Brubacher,G.,Hediger,H.,et al.The chemical composition and structure of deer antlers.Experientia,1953,9:138-140
[10]金顺丹,郑敏芝.鹿茸有效成分的研究(第一报).特产科学实验,1979,(4):24-28
[11]卞祖福,袁丽华,段传凤.三种驯鹿茸与梅花鹿茸的化学成分比较.特产科学实验,1985,4:49-52
[12]张经华,杨若明,张林源等.麋鹿梅花鹿和马鹿鹿茸中微量元素的分析测定.微量元素与健康研究,2000,17(4):39-40
[13]Silaev,A.B.,Katrukha,G.S.,Shampanova,O.M.,et al.Amino acid and mineral composition of antlers and pantocrine.Sbornik nauchnykh rabot nauchno-lssledovatel' skoi laboratotii pantovogo ollenevodstva,1969,2:29-32
[14]屈立新,唐越,王向东等.鹿茸精的心肌保护作用机理.中华实验外科杂志,1999,16(1):66-67
[15]谷天祥.心肌缺血再灌注Na~+-K~+ATPase活性变化及鹿茸精的保护作用.中国医科大学学报,1999,28(4):282-285
[16]孙晓波,周重楚.鹿茸精强壮作用的研究.中药药理与临床,1987,3:11-13
[17]张永和,黄晓巍,孙靖辉等.鹿茸醇提物对心肌梗死模型大鼠心肌损伤的保护作用及对血浆内皮素含量的影响.中国中药药信息杂志,2007,14(1):40-41
[18]潘麟士译.鹿茸的作用机理.福建医药杂志,1980,2(2):64
[19]徐惠波.鹿茸神经节甙酯对小鼠学习记忆功能的影响.中国药理学通报,1991,7(5):385-388
[20]陈晓光,杨明,王本祥等.人工培养鹿茸细胞的药理作用.中药药理与临床,1990,6 (1):30-32
[21]王岩,金淑莉,陈晓光.鹿茸胶囊抗惊厥和镇静作用的实验研究.长春中医学院学报,2003,19(2):31-32
[22]李立军,路来金,陈雷等.鹿茸多肽促进大鼠坐骨神经再生的实验研究.辽宁中医杂志,2004,31(4):343-344
[23]陈东,孟晓婷,刘佳梅等.鹿茸多肽对胎大鼠脑神经干细胞体外诱导分化的实验研究.解剖学报,2004,35(3):240-243
[24]孙晓波,周重楚.鹿茸精对机体免疫功能的影响.中成药研究,1986,2:24-25
[25]Wang BX,Zhao XH,Qi SB,et al.Effects of repeated administration of deer antler extract on biochemical changes related to aging in senescence acceleratedmice.Chem Pharm Bull.1988,36(7):2587-2592
[26]高云端,孙尚奎,李柏岩等.鹿茸精注射液性激素样作用的实验研究.中药药理与临床,1990,2:23-24
[27]田育璋,贺菊香,王丰梅等.鹿茸对大鼠睾丸影响的形态计量.青海医学院学报,1997,18(3):154-155
[28]杨若明,张经华,周素红等.麋鹿茸中的性激素对大鼠和小鼠生殖系统的影响.解剖学报,2001,32(2):180-182
[29]洪文,李建强,王照浩等.针灸治疗肾阳虚型男性不育症30例疗效观察.新中医,2002,34(5):39-40
[30]王家辉,张红梅,房景奎等.参茸配伍对腺嘌呤应用法雄性大鼠肾阳虚动物模型性腺损伤调整作用的实验研究.中华男科学,2004,10(4):315-319
[31]王本祥,刘爱晶,程秀娟.鹿茸多糖抗溃疡作用.药学学报,1985,5:321-325
[32]翁梁,周秋丽,王丽娟等.鹿茸多肽促进皮肤和成纤维细胞增殖及皮肤创伤愈合.药学学报,2001,36(11):817
[33]王岩,金淑莉,陈晓光.鹿茸胶囊抗炎镇痛作用的研究.吉林中医药,2003,23(6):48
[34]赵咏梅,陈晓光.鹿茸口服液抗炎、镇痛、免疫增强作用的实验研究.中国中医药科技,2005,12(2):128
[35]Allen Marion,Oberle Kathleen,Grace Michael,et al.Elk velvet antler in rheumatoid arthritis:phase Ⅱ trial.Biological research for nursing,2000,3(3):111-118
[36]Yeon-Kye Kim,Kyung-Sook Kim,Kang-Hyun Chung,et al.Inhibitory effects of deer antleraqua-acupuncture,the pilose antler of Cervus Korean Temminck var.mantchuricus Swinhoe,on type Ⅱ collagen-inducedarthritis in rats.International Immunopharmacology, 2003,3(7):1001-1010
[37]丁钰熊.鹿茸精注射液治疗血虚动物的实验研究.中成药,1991,1:27
[38]姚克霓.补血生髓胶囊药理作用的研究.基层中药杂志,1996,10(3):35-36
[39]陈莉萍,彭源贵,谢绍明等.参茸白凤膏的药理作用研究.中药药理与临床,1997,13(6):12-14
[40]潘勤.参桂鹿茸丸治疗慢性原发性低血压综合症35例.湖南中医药导报,1996,2(5):17
[41]陈书明,聂向庭,刘桂林等.鹿茸醇提物对白细胞减少动物模型影响初探.实验动物科学与管理,1999,16(4):32-33
[42]陈书明,聂向庭.鹿茸醇提物对用环磷酰胺处理的小白鼠红细胞免疫功能的影响.经济动物学报,2000,4(1):23-25
[43]丁长海,吴成义,魏伟等.鹿茸液的药理作用研究.安徽医科大学学报,1995,30(1):4-6
[44]梁贞爱,宋成岩,金忠吉.复方鹿茸煎剂对小鼠耐缺氧能力和抗疲劳作用的影响.中国医药科技,2002,9(3):152
[45]Shin,Kuk Hyun.,Yun-Choi,Hye Sook.,Lim,Soon Sung.,et al.Immuno-stimulating,anti-stress and anti-thrombotic effects of unossified velvet antlers.Natural product scienences,1999,5(1):54-59
[46]刘正才.从现代免疫学角度探讨中医药的抗衰老作用.浙江中医杂志,1981,16(6):272-275
[47]金光湖.鹿茸对氨甲喋吟引发的免疫功能低下的影响.黑龙江中医药,1993,2:40-42
f48]李志如.鹿角胶治疗急性乳腺炎的临床观察.中医杂志,1961,12(6):24-26
[49]连玉树.鹿茸的药理与临床.中医药学报,1988,6:41-46
[50]张廷良.张连仁治疗虚寒型脉管炎的经验.上海中医药杂志,1989,1:12-13
[51]唐巍然,于晓红,闻杰等.鹿茸多糖对免疫功能低下模型小鼠细胞免疫功能的影响.中国中医药科技,2000,7(4):234
[52]陈书明,聂向庭.鹿茸醇提物对白细胞减少小鼠模型腹腔吞噬细胞吞噬功能的影响.山西中医学院学报,2000,1(1):4-5
[53]丁克祥,陈华东.鹿茸的抗衰老作用及其机理.中国老年学杂志,1994,14(2):108-110
[54]Chen X.,Jia Y.,Wang B.Inhibitory effects of the extract of pilose antler on monoamine oxidase in aged mice.Zhongguo Zhongyao Zazhi,1992,17(2):107-110
[55]衣欣,李健民,袁慎萸等.肾阳虚模型大鼠与衰老的关系及鹿茸的作用.中药药理与临床,1997,13(5):34-35
[56]陈书明,聂向庭.鹿茸醇提物抗氧化作用的实验研究.实验动物科学与管理,2000,17(1):22-24
[57]葛迎春,李晨燕,任慧君等.鹿茸提取物和人参皂甙对衰老细胞的琥珀酸脱氢酶和多糖含量的影响.特产研究,2001,2:5-7
[58]王本祥,刘爱晶,程秀娟等.鹿茸多糖抗溃疡作用.药学学报,1985,5:321-325
[59]霍玉书,霍虹.鹿茸神经生长因子活性及促分化作用的研究.中药新药与临床药理,1997,8(2):79
[60]范玉林,邢增涛,卫功庆.鹿茸蛋白的提取分离及其抗肿瘤活性.经济动物学报,1998,2(1):27
[61]Kim,Dong-Hyun.,Park,Hae-Young.,Kim,Nam-Jae.,et al.Protective effect of antler in experimental colon carcinogenesis.Natural product sciences,1999,5(1):48-53
[62]Wang BX,Zhao XH,Qi SB,et al.Stimulating effect of deer antler extract on protein synthesis in senescence-accelerated mice in vivo.Inbid,1988,36(7):2593-2598
[63]Wang BX.Influence of the active compounds isolated from pilose antler on syntheses of protein and RNA in mouse liver.Yao Xue Xue Bao,1990,25(5):321-325
[64]陈书明,聂向庭,刘广金.鹿茸醇提物对环磷酰胺所致小鼠遗传物质损伤的影响.山西医科大学学报,2000,31(1):24-25
[65]刘秀梅,祁雪,陈晓光.鹿茸口服液降脂作用的研究.中药药理与临床,2003,19(6):38-39
[66]祁雪,刘秀梅,陈晓光.鹿茸口服液对小鼠实验性肝损伤的保护作用.中药药理与临床,2004,20(1):42-43
[67]余明泽,宋述辉,周毓.鹿茸对大鼠酒精性肝损害的拮抗作用.中国公共卫生学报,1996,15(3):172-173
[68]Kirn HS.Inhibitory effects of velvet antler water extract on morphine- induced conditioned place preference and DA receptor supersensitivety in mice.Ethnopharmacol,1999,66(1):25-31
[69]曹译.鹿茸对去卵巢大鼠所致骨质疏松症治疗作用的研究及鹿茸中硫酸软骨素的提取(硕士学位论文).长春:吉林大学,2005:49
[70]顾祖维.现代毒理学概论.北京:化学工业出版社,2005:157
[71]Shah H,Hartman SP,Weinhouse S.Formation of carbonyl chloride in carbon tetrachloride metabolism by rat liver in vetro.Cancer Res,1979,39:3942-3947
[72]Berger ML,Bhatt H,Combes B,et al.CCl_4-induced toxicity in isolated hepatocytes.Hepatology,1986,6:36-45
[73]Castro GD,Diaz Gomez MI,Castro JA.DNA bases attack by reactive metabolites produced during carbon terachloride biotransformation and promotion of liver microsomal lipid peroxidation.Res Commun Mol Pathol Pharmacol,1997,95:253-258
[74]Arosio B,Santambrogio D,Gagliano N,et al.Glutathione pretreatment lessens the acute liver injury induced by carbon tetrachloride.Pharmacol Toxicol,1997,81:164-168
[75]唐望先,虞涤霞,但自力等.肝炎平对大鼠慢性肝损害胶原纤维作用的实验研究.胃肠病学和肝病杂志,1998,7:167-169
[76]刘建文.药理实验方法学.北京:化学工业出版社,2004:168
[77]王淳,刘礼意,吉兰.D-氨基半乳糖盐酸盐诱发的肝损伤模型.中草药,1980,11(6):262-264
[78]Bessems JG,Vermeulen NP.Paracetamol(acetaminophen)-induced toxicity:Molecular and Biochemical Mechanisms,Analogues and Protective Approaches.Crit Rev Toxicol,2001,31(1):55-138
[79]Wang T,Shankar K,Ronis M,et al.Potentiation of thioacetamide liver injury in diabetic rat is due to induced CYP2E1.J Pharm Exp Ther,2000,294(2):473
[80]Gujral JS,Knight TR,Farhood A,et al.Mode of Cell Death after Acetaminophen Overdose in Mice:Apoptosis or Oncotic Necrosis Toxicol.Sci,2002,67(2):322-328
[81]Macrides TA,Naylor LM,Kalafatis N,et al.Hepatoprotective effects of the shark bile salt 5 beta-scymnol on acetam inophen-induced liver damage in mice.Fundam Appl Toxicol,1996,33:31-37
[82]Liu GT.Present status of anti-hepatitis drugs and its perspective.In:Society office of China Association for sciences and technology.Research on prevention and therapy of viral hepatitis.Beijing:Chin Sci Tech Press,1991:337-341
[83]邱英锋,缪晓辉,蔡雄等.卡介苗加脂多糖建立的大鼠急性免疫性肝损伤模型的研究.西北国防医学杂志,2004,25(5):345
[84]Tiegs G,Hentschel J,Wendel A.T Cell-dependent experimental liver injury in mice inducible by Concanavalin A.Clin Invest,1992,90:196-203
[85]李绍旦,袁本利.ConA诱导肝细胞损伤机理及CsA对其损伤的影响.胃肠病学和肝病学杂志,2004,13(5):471-474
[86]Dawei C,Robert J,Zeytun A,et al.CD44-deficient Mice Exhibit Enhanced Hepatitis after Concanavalin a Infection:Evidence for Involvenment of CD44 in Activaion-induced Cell Death.J Immunol,2001,166(10):5889-5897
[87]黄健,楼雅卿.酒精和肝脏.中国药物依赖性杂志.2000,9(2):88-90
[88]王明春,吴承荣,姜英.酒精性肝病的研究进展.Chin J clini Hepatol,1998,14(3):142-144
[89]Plaa GL.Chlorinated methanol and liver injury:highlights of the past 50 years.Annu Rev Pharmacol Toxicol,2000,4040-4065
[90]杨光华.病理学(第5版).北京:人民卫生出版社,2001:14
[91]江正辉,王泰龄.酒精性肝病.北京:中国医药科技出版社,2001:100-107
[92]Tsukamoto H,Tower SJ,Ciofalo LM,et al.Ethanol induced liver fibrosis in rats fed high-fat diet.Hepatology,1986,6:814-822
[93]赵静波,王泰龄,张晶等.大鼠急性酒精性肝损伤模型分析.中日友好医院学报,1996,10(1):17-19
[94]童英,姚小曼,吴少平.乙醇诱发急性肝损伤生物标记物的探讨.中国食品卫生杂志,1999,11:12-14
[95]长尾由纪子,叶木荣,赖小平.实验性肝损伤模型建立的初步探讨.广西中医药,2006,29(3):47-49
[96]唐云安,刘玉清,王国钦.肝损伤动物模型研究进展.卫生毒理学杂志,2002,16(04):236-238
[97]Kaplowitz N.Mechanisms of liver cell injury.J Hepatol,2000,32(1Suppl):39-47
[98]Patel T,Gores GJ.Apoptosis and hepatobiliary disease.Hepatolgy,1995,21(6):1725-1741
[99]Recknagel RO,Glende EA Jr,Dolak JA,Waller RL.Mechanisms of carbon tetrachloride toxicity.Pharmacol Ther,1989,43(1):139-154
[100]王鸿利.实验诊断学,人民卫生出版社,2001:49
[101]詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报,2006,41(6):664-666
[102]罗文,杜芳腾,刘晶美.实验性大鼠肝损伤肝组织铜锌变化研究.江西医学院学报,1998,38(2):21-23
[103]李烨.双环醇对实验性肝损伤、肝纤维化的保护作用和保护机制的研究(博士学位论文).北京:中国协和医科大学中国医学科学院,2001:71-72,51
[104]陈诗书.医学生物化学.北京:科学出版社,2005,366-372,123-124
[105]唐丽英.血清总胆汁酸与胆红素在肝胆疾病中的相关关系探讨.南华大学学报,2002,30(3):296-297
[106]贺巾超.rhKD/APP的制备和对肝损伤保护的研究(博士学位论文).吉林大学,2006:83
[107]黄梅芳,朱龙庆.酒精性肝病发病机制的研究进展.医学新知杂志,2003,13(2):104
[108]Yamagchi Y,Okabe K,Matsumoto F,et al.Peroxynitrite formation during rat hepatic allograft rejection.Hepatology,1999,29:777
[109]Li J,Sun M,Hsn M.NO、SOD and NOS in injuried liver of fetus rat with intrauterine asphyxia.Shijie Huaren xiaohua Zazhi,2002,10(2):177-181
[110]赵铁建,钟振国,方卓等.白花丹水煎液对四氯化碳慢性肝损伤小鼠肝组织脂质过氧化的影响.广西医科大学学报,2006,23(5):725-726
[111]李宏涛,陈国民.D-氨基半乳糖研究的回顾和展望.肝脏,2004,9(3):209-210
[112]尹家乐,李心,张士侠等.白首乌C21甾体酯苷对小鼠急性四氯化碳肝损伤的保护作用.安徽医药,2007,11(3):198-200
[113]Jaeschke H,Gores GJ,Cederbaum AI,et al.Ycchanism of hepatotoxicity.Toxicol Sci,2002,65:166-176
[114]Chen J,Robinson NC,Schenker S,et al.Formation of 4-hydroxynonenal adducts with cytochrome C oxidase in rats following short-term ethanol intake.Hepatology,1999,29:1792-1798
[115]Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem,2000,275:2247-2250
[116]王宪龄,张丽萍,李连珍等.柴胡黄芩配伍不同提取部位对扑热息痛所致小鼠急性肝损伤的保护作用.中药药理与临床,2005,21(3):10-11
[117]Macrides TA,Naylor LM,Kalafatis N,et al.Hepatoprotective effects of the shark bile salt 5beta2scymnol on acetaminophen-induced liver damage in mice.Fundam Appl Toxicol,1996,33:31-37
[118]Hinson JA,Pike SL,Pumfrd NR,et al.Nitrotyrosine-protein adducts in hepatic centrilobular areas following toxic does of acetaminophen in mice.Chem Res Toxicol,1998,11:604-607
[119]王小丽,黄真,江丽霞等.黄花倒水莲提取物对小鼠实验性肝损伤的保护作用.时珍国医国药,2007,18(6):1320-1321
[120]刘春棋,卑占宇,李洪亮等.六月雪水提取物对小鼠实验性肝损伤的保护作用.赣南医学院学报,2006,26(6):824-825
[121]吴丽,魏伟.肝纤维化的动物模型及治疗药物研究.中国药理学通报,2004,20(5):481-485
[122]Potter W.Z.,Davis D.C.,Mitchell J.R.,et al.Acetaminophen-induced hepatic necrosis.Ⅲ.Cytochrome P450-mediated covalent binding in vitro.J Pharmacol Exp Ther,1973,187:203
[123]Critchley Julian,汪德清,丁保国等.黄芪总黄酮对扑热息痛所致肝损伤的防护机理探讨.中国中药杂志,2001,26(9):617-620
[124]刘钺,张朝明,郝玲等.血清总胆红素、甘氨胆酸、甲胎蛋白、糖类抗原19-9与胆汁瘀滞相关性评价.国际放射医学核医学杂志,2006,30(2):107-109
[125]吴建华,李波.舒肝灵对小鼠实验性肝损伤的防护作用.中西医结合肝病杂志,2000,10(3):27-28
[126]饶光宇,陈秀芬,张高等.迷迭香二萜酚提取物对几种肝损伤的保护作用.中草药,2001,32(5):434-436
[127]饶光宇,陈秀芬,于燕妮.茶多酚对小鼠实验性肝损伤的保护作用.中国中药杂志,2001,26(3):191-193
[128]汪德清,沈文梅,田亚平等.黄芪活性提取成分对膜脂质过氧化损伤的防护作用.中国中药杂志,1996,21(12):746-748
[129]Blazka ME,Wilmer JL,Holladay SD,et al.Role of proinflammatory cytokines in acetaminophen hepatotoxicity.Toxicol Appl Pharmacol,1995,133(1):43-45
[130]Kitamura K,Nakamoto Y,Akiyama M,et al.Pathogenic roles of tumor necrosis factor p55-mediated signals in dimethylnitrosamine-induced murine liver fibrosis.Lab Invest,2002,82(5):571-583
[131]Simpson KJ,Lukacs NW,McGregor AH,et al.Inhibition of turnout necrosis factor alpha does not prevent experimental paracetamol-induced hepatic necrosis.J.Pathol,2000,190(4):489-494
[132]Boess F,Bopst M,Althaus R,et al.Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-alpha gene Knockout mice.Hepatology,2001,27(4):1021-1029
[133]Gardner CR,Laskin JD,Dambach DM,et al.Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1 Potential role of inflammatory mediators.Toxicol Appl Pharmacol,2003,192(2):119-130
[134]巴吐尔.草棉花花瓣不同提取物的保肝及体外溶栓作用(硕士学位论文).乌鲁木齐:新疆医科大学学报,2005:11-13
[135]汪五三,宋建国.芝麻素保肝作用实验研究.中药药理与临床,2006,22(3):27-32
[136]Fang C,Lindros KO,Badger TM,et al.Zonated expression of cytokines in rat liver:effect of chronic ethanol and the cytochrome P450 2E1 inhibitor,chlormethiazole.Hepatology,1998,27:1304-1310
[137]Kukielka E,Dicker E,Cederbaum AI.Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment.Arch Biochem Biophys,1994,309(2):377-386
[138]Reinke LA,Moore DR,Mccay PB.Free radical formation in liver of rats treated acutely and chronically with alcohol.Alcohol Clin Exp Ther,1997,21(4):642-646
[139]Slomiany A,Piotrowski E,Grabska M,et al.Chronic ethanol-initiated apoptosis in hepatocytes is induced by changes in membrane biogenesis and intracellular transport.Alcohol Clin Exp Ther,1999,23(2):334-343
[140]倪力强.柴枳合剂治疗慢性酒精性肝损伤大鼠的实验研究(博士学位论文).沈阳:辽宁中医学院,2001:9-10
[141]叶永安,田德禄.慢肝消对大鼠酒精性肝损伤血清生化的影响.北京中医药大学学报,1999,22(6):31-32
[142]赵初环,卢中秋,李惠萍等.大鼠酒精性肝病模型的建立.浙江临床医学,2007,9(4):435-436
[143]王杰,姚凤云,杨伟鹏等.肝加欣片治疗酒精性肝病的实验研究.中国实验方剂学杂志,2006,12(8):39-40
[144]关光玉,曾家慧,张术斌等.酒精性脂肪肝小鼠模型的建立.宁夏医学杂志,2007,29(11):971-973
[145]曹阳.门冬氨酸鸟氨酸治疗酒精性肝病的临床疗效评价.实用肝脏病杂志,2007,10(3):194-195
[146]杜施霖,迟宝荣.龙牙葱木皂苷对大鼠酒精性肝病的防治作用.吉林大学学报,2005,31(1):64-67
[147]Niemela O,Parkkila S,Britton RS,et al.Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.J-Lab-Clin-Med,1999,133(5):451-460
[148]李颖.阿魏酸钠和当归醇沉物对免疫性肝损伤的干预作用.中草药,2000,31(4):274-276
[149]陈道荣,王丕龙.一氧化氮与酒精性肝病.胃肠病学和肝病学杂志,2003,12(4):392-394
[150]古赛.枸杞多糖防治大鼠酒精性脂肪肝的实验研究(博士学位论文).重庆:重庆医科大学,2007:28-29
[151]Oneta CM,Simanowski UA.First pass metabolism of ethanol is strikingly influenced by the speed of gastric empty.Gut,1996,43(5):612-619
[152]潘年松,黄勋,王毅等.护肝灵对实验大鼠酒精性脂肪肝的影响与机制探讨.陕西中医,2007,28(9):1265-1268
[153]毕业东,郭富成,张德祥.葛柏解酒液防治小鼠急性酒精中毒作用机理.实验研究,2005,17(5):50-51
[154]杨牧祥,于文涛,胡金宽等.酒速愈对急性酒精中毒小鼠解酒作用及酒精代谢的影响.中外健康文摘(医药月刊),2007,4(3):37-39
[155]Wang GS,Liu GT.Role of nitric oxide in immunological liver damage in mice.Biochem Pharmacol,1995,49(9):1277-1281
[156]黄玲.急性肝损伤和免疫性肝损伤动物模型研究述评.广州中医药大学学报,1998,15:67-69
[157]Hishinuma I,Nagakawa J,Hirots K,et al.Involvement of turmr necrosis factor in development of hepatic injury ingalac-to-samine-sensitized mice.Hepatology,1990,12:1187
[158]肖刚,王勤.罗汉果甜苷对小鼠实验性肝损伤保护作用的研究.中国药房,2008,19(3):163-165
[159]徐强,李庆云,吕凤娟,桑希生.牡蛎汤对免疫性肝损伤小鼠血清ALT、AST和肝组织TNF-a的影响.中国中医基础医学杂志,2008,14(2):104-105
[160]毛爱红,张昱,赵祁等.秃疮花提取物对小鼠免疫性肝损伤的保护作用.中国药理学通报,2004,20(8):940-943
[161]张慧娜,李诚秀,黄能慧等.汉丹肝乐对免疫性肝纤维化的预防作用.贵州医药,2001,25(5):415-417
[162]王天然,曾祥元,马布仁.硬肝复康对小鼠免疫性肝损伤的作用.成都中医药大学学报,2002,25(2):18-20
[163]万丽,万兴旺,胡晋红.绞股蓝总皂苷对免疫性肝纤维化大鼠肝功能和肝纤维化的影响.第二军医大学学报,2003,24(12):1319-1321
[164]洪素兰,杨敏,梁鹤,邵雷.肝舒乐片抗大鼠免疫性肝纤维化作用机制的实验研究. 光明中医,2005,20(5):45-47
[165]王明宇,林志彬.灵芝三萜类成分在体内外对小鼠免疫性肝损伤的影响.中国药学杂志,2000,35(12):808-811
[166]Cross CE.Oxygen RADecals and human disease.Ame inter Med,1987,107(4):526
[167]林志椿,聂松青.细胞膜的流动性.生理科学进展,1985,16(1):82-89
[168]Lwao K,Soichivo,Hajime H,et al.Increased intric Oxise Synthase activityas cause of mitochondrial dysfunction in rat hepatocytes.Hepatotogy,1996,24:1185
[169]Debra L,Marina R,Diane E,et al.Hipatic nitric oxide production following acute endotoxemia in rats is mediated by increased indue ible nitric oxide syt=nthas geneexpression.Hepatology,1995,22(1):223
[170]Yabuki M,Inai Y,Yoshika T,et al.Oxygen-dependent fragmentation of cellular DNA by nitric oxide.Free Radic Res,1997,26:245
[171]商玉萍,方士英,葛金芳等.虫草多糖对小鼠免疫性肝损伤的保护作用.华西药学杂志,2007,22(6):654-655
[172]胡成穆,姜辉,刘洪峰等.金银花总黄酮对小鼠免疫性肝损伤的保护作用.中药药理与临床,2007,23(5):85-88
[173]桑希生,李庆云,徐强.牡蛎汤对免疫性肝损伤小鼠肝组织NO、IL-2和TNF-a的影响.中医药信息,2007,24(5):68-69
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |