淡豆豉与栀子配伍降低栀子肝脏毒性的研究
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摘要
目的:采用整体动物实验及血清药理学的方法观察淡豆豉对栀子肝脏毒性的减毒作用。方法:大鼠随机分为正常对照组、栀子组(11.7g/kg)、栀子淡豆豉配伍组(23.4g/kg,配伍比例1:1)、栀子苷组(0.15g/kg),各组灌胃给予相应药物,每天1次,连续7天,实验结束测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)活性、总胆红素(TBIL)含量;计算肝脏系数,HE染色观察肝组织结构变化。制备各组含药血清,血清浓度10%,检测人肝癌Hep G2细胞存活率及氧化应激水平:胞内锰-超氧化物歧化酶(Mn-SOD)活性、活性氧(ROS)及丙二醛(MDA)含量。结果:与正常对照组相比,栀子组(11.7g/kg)及栀子苷组(0.15g/kg)大鼠体重增长明显缓慢,两组各有两只动物死亡;血清ALT、AST、ALP、TBIL水平显著升高;肝脏系数明显上升,HE染色可见明显的肝细胞肿胀坏死及炎细胞浸润;细胞存活率、Mn-SOD活性显著下降;ROS水平、MDA含量显著上升。与栀子组比较,栀子淡豆豉配伍组(23.4g/kg)大鼠体重增长明显较快;ALT、AST、ALP、TBIL水平及肝脏系数均显著下降,肝组织病理也未见明显异常;细胞存活率、Mn-SOD活性显著增高,ROS、MDA含量明显下降。结论:淡豆豉与栀子配伍可降低栀子肝脏毒性,其机制可能与降低肝细胞的氧化应激水平有关。
Objective: To observe the detoxification of Sojae Semen Preparatum on liver toxicity induced by Gardeniae Fructus by the animal experiment and serum pharmacologic method. Methods: Rats were randomly divided into the control group,Gardeniae Fructus group( 11. 7g/kg),compatibility of Gardeniae Fructus and Sojae Semen Preparatum group( 23. 4g/kg,compatibility proportion1: 1),geniposide group( 0.15g/kg). Animals were treated with corresponding drugs by intragastrical administration,once a day for 7 days,and one hour after the last adminstration,the alanine aminotransferase( ALT),aspartate transaminase( AST),alkaline phosphatase( ALP),total bilirubin( TBIL)content were detected; the liver index was calculated,histopathological changes of liver tissue were observed by HE staining. All groups of serum containing drug were prepared( serum concentration 10%),survival rates of Hep G2 cells and levels of oxidative stress were measured: manganese superoxide dismutase( Mn-SOD) activity,malondialdehyde( MDA) and reactive oxygen species( ROS) content. Results:Compared with the control group,Gardeniae Fructus( 11. 7g/kg) and geniposide( 0. 15g/kg) obviously decreased weight gain( P < 0. 01),obviously increased levels of ALT,AST,ALP,TBIL and liver index( P < 0. 01),the rat liver cell was swelling,necrosis and inflammatory cell infiltration,and two animals died in each group; Gardeniae Fructus and geniposide also obviously decreased survival rates and Mn-SOD activity( P < 0. 01),increased levels of ROS and MDA( P < 0. 01). Compared with Gardeniae Fructus group,body weights of rats rapidly increased in the compatibility of Gardeniae Fructus and Sojae Semen Preparatum group( 23. 4g/kg)( P < 0. 01); levels of ALT,AST,ALP,TBIL and liver index were significantly decreased( P < 0. 05 or P < 0. 01),no obvious abnormality in liver histopathology was found; survival rates and Mn-SOD activity were significantly increased( P < 0. 05 or P < 0. 01),levels of ROS and MDA significantly decreased( P < 0. 01).Conclusion: Sojae Semen Preparatum can significantly alleviate the liver toxicity induced by Gardeniae Fructus,the mechanism might be related to reducing the level of oxidative stress in liver cells.
Objective: To observe the detoxification of Sojae Semen Preparatum on liver toxicity induced by Gardeniae Fructus by the animal experiment and serum pharmacologic method. Methods: Rats were randomly divided into the control group,Gardeniae Fructus group( 11. 7g/kg),compatibility of Gardeniae Fructus and Sojae Semen Preparatum group( 23. 4g/kg,compatibility proportion1: 1),geniposide group( 0.15g/kg). Animals were treated with corresponding drugs by intragastrical administration,once a day for 7 days,and one hour after the last adminstration,the alanine aminotransferase( ALT),aspartate transaminase( AST),alkaline phosphatase( ALP),total bilirubin( TBIL)content were detected; the liver index was calculated,histopathological changes of liver tissue were observed by HE staining. All groups of serum containing drug were prepared( serum concentration 10%),survival rates of Hep G2 cells and levels of oxidative stress were measured: manganese superoxide dismutase( Mn-SOD) activity,malondialdehyde( MDA) and reactive oxygen species( ROS) content. Results:Compared with the control group,Gardeniae Fructus( 11. 7g/kg) and geniposide( 0. 15g/kg) obviously decreased weight gain( P < 0. 01),obviously increased levels of ALT,AST,ALP,TBIL and liver index( P < 0. 01),the rat liver cell was swelling,necrosis and inflammatory cell infiltration,and two animals died in each group; Gardeniae Fructus and geniposide also obviously decreased survival rates and Mn-SOD activity( P < 0. 01),increased levels of ROS and MDA( P < 0. 01). Compared with Gardeniae Fructus group,body weights of rats rapidly increased in the compatibility of Gardeniae Fructus and Sojae Semen Preparatum group( 23. 4g/kg)( P < 0. 01); levels of ALT,AST,ALP,TBIL and liver index were significantly decreased( P < 0. 05 or P < 0. 01),no obvious abnormality in liver histopathology was found; survival rates and Mn-SOD activity were significantly increased( P < 0. 05 or P < 0. 01),levels of ROS and MDA significantly decreased( P < 0. 01).Conclusion: Sojae Semen Preparatum can significantly alleviate the liver toxicity induced by Gardeniae Fructus,the mechanism might be related to reducing the level of oxidative stress in liver cells.
引文
1任艳青,李葆林,田宇柔,等.栀子、连翘等中药配方颗粒体外肝细胞毒性研究.河北中医药学报,2017;32(1)∶43~46
2王坤,金若敏,陈长勋.茵陈蒿汤与栀子肝毒性的比较研究.中药药理与临床,2013;29(1)∶8~12
3王坤,金若敏,陈长勋.栀子与黄连解毒汤肝毒性的比较研究.中国中药杂志,2013;38(14)∶2365~2369
4任艳青,田宇柔,李琛,等.京尼平苷及其体内代谢产物京尼平对Hep G2细胞毒性的比较及机制研究.中国药理学通报,2016;32(12)∶1755~1761
5王安军,王兴华.栀子豉汤及其组成中药近5年研究进展.江西中医学院学报,2013;25(5)∶97~100
6田义龙,赵静,任艳青,等.栀子豉汤对胰岛素抵抗的改善作用及机制研究.中药药理与临床,2010;26(6)∶5~7
7李琛,赵静,冯薇,等.栀子豉汤对自发性高血压大鼠AT1受体mR-NA表达的影响.中药药理与临床,2012;28(6)∶1~3
8赵佳伟,何家乐,等.参附配伍减毒作用的尿液代谢组学研究.中药药理与临床,2015;31(1)∶1~5
9谢彤,周学平,林丽丽,等.基于"异类相制"的雷公藤复方配伍减毒代谢组学研究.中国中药杂志,2016;4(16)∶1124~1129
10周聪,周玲玲,柳璋璞,等.基于肝毒性的雷公藤复方配伍减毒作用及机制研究.中药药理与临床,2013;29(5)∶106~109
11陈宇征,吕文良.中药导致药物性肝损伤的机制研究进展.中国中医基础医学杂志,2015;21(11)∶1476~1478
12牛丽颖,任艳青,王鑫国.淡豆豉异黄酮对增殖血管平滑肌细胞JAK2/STAT3信号转导通路的影响.中国药理学通报,2009;25(11)∶1487~1490
13刘姣,田义龙,王益红,等.淡豆豉提取物对2型糖尿病大鼠主动脉i NOS,e NOS mRNA表达的影响.大豆科学,2012;31(1)∶115~118
14牛丽颖,王鑫国,任艳青,等.淡豆豉提取物对去卵巢骨质疏松大鼠骨微细结构的改善作用.中成药,2010;32(11)∶1874~1876
15任艳青,李清,刘姣,等.淡豆豉异黄酮对AngⅡ诱导大鼠血管平滑肌细胞周期的影响.中药药理与临床,2011;27(3)∶44~47
16刘姣,田义龙,李琛,等.淡豆豉异黄酮浓缩物对大鼠胰岛素抵抗的改善作用.食品工业科技,2012;33(10)∶347~361
17邹丽秋,王彩霞,匡雪君,等.黄酮类化合物合成途径及合成生物学研究进展.中国中药杂志,2016;41(22)∶4124~4128
18杨洪军,付梅红,吴子伦,等.栀子对大鼠肝毒性的实验研究.中国中药杂志,2006;31(13)∶1091~1093
2王坤,金若敏,陈长勋.茵陈蒿汤与栀子肝毒性的比较研究.中药药理与临床,2013;29(1)∶8~12
3王坤,金若敏,陈长勋.栀子与黄连解毒汤肝毒性的比较研究.中国中药杂志,2013;38(14)∶2365~2369
4任艳青,田宇柔,李琛,等.京尼平苷及其体内代谢产物京尼平对Hep G2细胞毒性的比较及机制研究.中国药理学通报,2016;32(12)∶1755~1761
5王安军,王兴华.栀子豉汤及其组成中药近5年研究进展.江西中医学院学报,2013;25(5)∶97~100
6田义龙,赵静,任艳青,等.栀子豉汤对胰岛素抵抗的改善作用及机制研究.中药药理与临床,2010;26(6)∶5~7
7李琛,赵静,冯薇,等.栀子豉汤对自发性高血压大鼠AT1受体mR-NA表达的影响.中药药理与临床,2012;28(6)∶1~3
8赵佳伟,何家乐,等.参附配伍减毒作用的尿液代谢组学研究.中药药理与临床,2015;31(1)∶1~5
9谢彤,周学平,林丽丽,等.基于"异类相制"的雷公藤复方配伍减毒代谢组学研究.中国中药杂志,2016;4(16)∶1124~1129
10周聪,周玲玲,柳璋璞,等.基于肝毒性的雷公藤复方配伍减毒作用及机制研究.中药药理与临床,2013;29(5)∶106~109
11陈宇征,吕文良.中药导致药物性肝损伤的机制研究进展.中国中医基础医学杂志,2015;21(11)∶1476~1478
12牛丽颖,任艳青,王鑫国.淡豆豉异黄酮对增殖血管平滑肌细胞JAK2/STAT3信号转导通路的影响.中国药理学通报,2009;25(11)∶1487~1490
13刘姣,田义龙,王益红,等.淡豆豉提取物对2型糖尿病大鼠主动脉i NOS,e NOS mRNA表达的影响.大豆科学,2012;31(1)∶115~118
14牛丽颖,王鑫国,任艳青,等.淡豆豉提取物对去卵巢骨质疏松大鼠骨微细结构的改善作用.中成药,2010;32(11)∶1874~1876
15任艳青,李清,刘姣,等.淡豆豉异黄酮对AngⅡ诱导大鼠血管平滑肌细胞周期的影响.中药药理与临床,2011;27(3)∶44~47
16刘姣,田义龙,李琛,等.淡豆豉异黄酮浓缩物对大鼠胰岛素抵抗的改善作用.食品工业科技,2012;33(10)∶347~361
17邹丽秋,王彩霞,匡雪君,等.黄酮类化合物合成途径及合成生物学研究进展.中国中药杂志,2016;41(22)∶4124~4128
18杨洪军,付梅红,吴子伦,等.栀子对大鼠肝毒性的实验研究.中国中药杂志,2006;31(13)∶1091~1093
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