黄芩苷锌对大鼠免疫性肝损伤的保护作用及意义
摘要
[目的]：运用卡介苗联合脂多糖建立大鼠免疫性肝损伤模型,给予实验组治疗剂量的黄芩苷锌灌胃处理,观察用药后实验组大鼠的一般情况及生化指标的变化和转归过程,探讨黄芩苷锌对大鼠免疫性肝损伤的保护作用、机理及意义,为治疗肝损伤提供理论支持,并为今后的临床用药提供了更多的选择。
[方法]：1.将实验大鼠70只(雌雄各半)随机分为空白对照组A(10只)黄芩苷给药组B(15只)黄芩苷锌给药组C(15只)还原型谷胱甘肽(占拉定)组D(15只)与模型组E(15只)。
2.采用卡介苗联合脂多糖腹腔注射建立大鼠免疫性肝损伤模型。首先除空白组外,各组均给予卡介苗致敏,实验组同时给予相应药物处理,空白组和模型组给予溶媒灌胃。第11天除空白组外,给药组与模型组给予脂多糖腹腔注射。24小时后行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。
3.接着各组继续给予相应药物处理。并将实验组和模型组分别分为1、2两组。1组再次给予脂多糖攻击,2组继续相应药物处理。10天后行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。除A、E组外,各组继续给予等容积相应药物处理,以10天为一周期,最后再行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。
所得结果用SPSS软件行统计学分析。
[结果]：大鼠免疫性肝损伤模型建立成功。第11天注射脂多糖后24小时,与空白对照组A比较,模型组E组大鼠ALT、AST升高明显(P<0.05),肝匀浆组织GSH-Px降低(P0.05)。给药组间相互比较无统计学差异。第二十天继续灌胃但未给予LPS再处理的大鼠B2、C2、D2、E2与十天前经脂多糖攻击后的ALT、AST和GSH-Px数值指标行自身对照在C2、D2组均有统计学意义。C2组分别与B2、D2、E2组及空白对照A组间比较,ALT、AST值在A、B2和E2组间有统计学意义(P<0.05)。GSH-Px值在C2与E2、空白对照组A之间有统计学差异。第三十天,经过LPS再处理的B1、C1、D1、与El组及空白A组比较ALT、AST、GSH-Px均有统计学意义。C1分别与B1、E1比较GSH-Px有意义,Cl与D1比较GSH-Px无意义。同时病理切片观察,经过黄芩苷,黄芩苷锌,古拉定灌胃处理的实验组,随着治疗时间的推移,肝脏炎症损伤情况较单纯模型E组有减轻,肝内CYP2E1含量有所提高。
[结论]：在卡介苗致敏同时给予药物干预处理的大鼠,再接受脂多糖激发所致炎症因子损伤情况下,肝功损伤情况较未处理的模型组轻,黄芩苷锌能提高机体抗氧化能力,减轻免疫复合物的细胞毒作用从而减轻肝脏损伤,并在一定时间窗内,抗氧化作用的相关生化指标较黄芩苷用药组作用强,与传统治疗肝损伤药物还原型谷胱甘肽(古拉定)相比作用相当,为中药治疗肝损伤提供了理论依据,并为今后治疗肝损伤临床用药提供了更多的选择。
Objective:To build model of immunological liver injury in rats, we use BCG plus LPS The experimental group given therapeutic doses of Baicalin Zinc by gastric irrigation, and then we observed the general situiation,biochemical parameters and maturity process. To provide theoretical support and more choice for clinical medication, we study the protectional roles, mechanisms and significance of Baicalin Zinc on immunological liver injury in rats.
Methods:1、the 70 rats were randomly divided into blank control group A(10 cases), baicalin group B (15 cases), Baicalin Zinc group C (15 cases), Reduced Glutathione Sodium group D (15 cases) and model group E (15 cases).
2、To build model of immunological liver injury in rats, we use BCG plus LPS. First, escept the blank control group, all the other groups were sensitized by given BCG, meanwhile, given the appropriate drugs, but the blank control group A and model group E were given CMC-Na by gastric irrigation. All the groups, except the blank control group, were given LPS by intraperitoneal injection at the 11th day. After 24 hours, we tested the GSH-Px of the hepatic tissue, ALT and AST. At the same time, we obversed the pathological sections which were made of the right lobe of liver tissue, and the liver tissue were studied on by immunohistochemictry.
3、Then, all the groups were given the appropriate drugs. The drug given groups and the model group were divided into group 1 and group 2. The rats in the group 1 were given LPS again; the group 2 were given the appropriate drugs contiuntly.10 days latter, we tested the GSH-Px of the hepatic tissue, ALT and AST., meanwhile, we obversed the pathological sections which were made of the right lobe of liver tissue, and the liver tissue were studied on by immunohistochemictry. Excepting blank control group A and model group E, other groups continued to give the appropriate drugs,10 days as a cycle. At last,we did all the tests as usual.
All the datas were anaiyized by SPSS software.
Result:The immunological liver injury model was builded sucessfully.24 hours after injected LPS at the 11th days, the ALT and AST of the model group were both more than the blank, but the GSH-Px is less. The difference had statistical significance(P<0.05). The three drug given groups were compared with the model group one by one, the results showed that the difference in AST and ALT had statistical significance(P<0.05), though the GSH-Px is more than the model group, there is no statistical significance between them. The difference between the three drug given groups had no statistical significance. And then compared with the 11th days, at the 20 days, the group 2 of the drug given groups were given the drugs, but no LPS. The numbers of ALT, AST and GSH-Px in Baicalin Zinc group and Reduced Glutathione Sodium group is more different.The numbers of the 20 days, there were statistical significance between group 2 of the Baicalin Zinc group C and baicalin group, group 2 of the Baicalin Zinc group and the model, group 2 of the Baicalin Zinc group and the blank((P<0.05); the GSH-Px is different in the last two above. At the 30 days, the differents of AST, ALT and GSH-Px between the group 1 of the drug given and the model groups and the blank had statistical significance, but the number between the group 1 of the Baicalin Zinc group and the group 1 of the Reduced Glutathione Sodium group were no sigificant different. Observeing the pathological sections, the inflammatory injury of the liver in the drug given groups is weakless than the model group, and the quantity of the CYP2E1 is a little higher than the model group.
Conclusion:The rats were dealed with BCG and appropriate drugs, and then given LPS, which induced the immunological liver injury were found. The injury of the liver is less than the model group.Baicalin Zinc can improve the antioxidant capacity, and reduce the cytotoxicity of the immune complexes,so it can reduce the injury of the liver. At the same time, the antioxidant capacity of the Baicalin Zinc is more than the role of baicalin, and as same as the Reduced Glutathione Sodium. The Baicalin Zinc is another choice of drugs which is usfull of protecting liver in clinical.
[方法]：1.将实验大鼠70只(雌雄各半)随机分为空白对照组A(10只)黄芩苷给药组B(15只)黄芩苷锌给药组C(15只)还原型谷胱甘肽(占拉定)组D(15只)与模型组E(15只)。
2.采用卡介苗联合脂多糖腹腔注射建立大鼠免疫性肝损伤模型。首先除空白组外,各组均给予卡介苗致敏,实验组同时给予相应药物处理,空白组和模型组给予溶媒灌胃。第11天除空白组外,给药组与模型组给予脂多糖腹腔注射。24小时后行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。
3.接着各组继续给予相应药物处理。并将实验组和模型组分别分为1、2两组。1组再次给予脂多糖攻击,2组继续相应药物处理。10天后行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。除A、E组外,各组继续给予等容积相应药物处理,以10天为一周期,最后再行ALT、AST和肝组织GSH-Px测定,同时取肝右叶组织做病理切片观察和免疫组化处理。
所得结果用SPSS软件行统计学分析。
[结果]：大鼠免疫性肝损伤模型建立成功。第11天注射脂多糖后24小时,与空白对照组A比较,模型组E组大鼠ALT、AST升高明显(P<0.05),肝匀浆组织GSH-Px降低(P
[结论]：在卡介苗致敏同时给予药物干预处理的大鼠,再接受脂多糖激发所致炎症因子损伤情况下,肝功损伤情况较未处理的模型组轻,黄芩苷锌能提高机体抗氧化能力,减轻免疫复合物的细胞毒作用从而减轻肝脏损伤,并在一定时间窗内,抗氧化作用的相关生化指标较黄芩苷用药组作用强,与传统治疗肝损伤药物还原型谷胱甘肽(古拉定)相比作用相当,为中药治疗肝损伤提供了理论依据,并为今后治疗肝损伤临床用药提供了更多的选择。
Objective:To build model of immunological liver injury in rats, we use BCG plus LPS The experimental group given therapeutic doses of Baicalin Zinc by gastric irrigation, and then we observed the general situiation,biochemical parameters and maturity process. To provide theoretical support and more choice for clinical medication, we study the protectional roles, mechanisms and significance of Baicalin Zinc on immunological liver injury in rats.
Methods:1、the 70 rats were randomly divided into blank control group A(10 cases), baicalin group B (15 cases), Baicalin Zinc group C (15 cases), Reduced Glutathione Sodium group D (15 cases) and model group E (15 cases).
2、To build model of immunological liver injury in rats, we use BCG plus LPS. First, escept the blank control group, all the other groups were sensitized by given BCG, meanwhile, given the appropriate drugs, but the blank control group A and model group E were given CMC-Na by gastric irrigation. All the groups, except the blank control group, were given LPS by intraperitoneal injection at the 11th day. After 24 hours, we tested the GSH-Px of the hepatic tissue, ALT and AST. At the same time, we obversed the pathological sections which were made of the right lobe of liver tissue, and the liver tissue were studied on by immunohistochemictry.
3、Then, all the groups were given the appropriate drugs. The drug given groups and the model group were divided into group 1 and group 2. The rats in the group 1 were given LPS again; the group 2 were given the appropriate drugs contiuntly.10 days latter, we tested the GSH-Px of the hepatic tissue, ALT and AST., meanwhile, we obversed the pathological sections which were made of the right lobe of liver tissue, and the liver tissue were studied on by immunohistochemictry. Excepting blank control group A and model group E, other groups continued to give the appropriate drugs,10 days as a cycle. At last,we did all the tests as usual.
All the datas were anaiyized by SPSS software.
Result:The immunological liver injury model was builded sucessfully.24 hours after injected LPS at the 11th days, the ALT and AST of the model group were both more than the blank, but the GSH-Px is less. The difference had statistical significance(P<0.05). The three drug given groups were compared with the model group one by one, the results showed that the difference in AST and ALT had statistical significance(P<0.05), though the GSH-Px is more than the model group, there is no statistical significance between them. The difference between the three drug given groups had no statistical significance. And then compared with the 11th days, at the 20 days, the group 2 of the drug given groups were given the drugs, but no LPS. The numbers of ALT, AST and GSH-Px in Baicalin Zinc group and Reduced Glutathione Sodium group is more different.The numbers of the 20 days, there were statistical significance between group 2 of the Baicalin Zinc group C and baicalin group, group 2 of the Baicalin Zinc group and the model, group 2 of the Baicalin Zinc group and the blank((P<0.05); the GSH-Px is different in the last two above. At the 30 days, the differents of AST, ALT and GSH-Px between the group 1 of the drug given and the model groups and the blank had statistical significance, but the number between the group 1 of the Baicalin Zinc group and the group 1 of the Reduced Glutathione Sodium group were no sigificant different. Observeing the pathological sections, the inflammatory injury of the liver in the drug given groups is weakless than the model group, and the quantity of the CYP2E1 is a little higher than the model group.
Conclusion:The rats were dealed with BCG and appropriate drugs, and then given LPS, which induced the immunological liver injury were found. The injury of the liver is less than the model group.Baicalin Zinc can improve the antioxidant capacity, and reduce the cytotoxicity of the immune complexes,so it can reduce the injury of the liver. At the same time, the antioxidant capacity of the Baicalin Zinc is more than the role of baicalin, and as same as the Reduced Glutathione Sodium. The Baicalin Zinc is another choice of drugs which is usfull of protecting liver in clinical.
引文
1、张喜平,田华,程琪辉,黄岑苷的药理作用研究现状中国药理学通报2003 Nov19(11)：1212-1215
2、杨晖,刘旭黄岑苷锌研究进展 昆明医学院学报2007,(3)：106-109
3、李延峰,梁绍荣,耿辉 黄岑苷金属配合物的研究进展【J】时珍国药,1999 10(2)：152-153
4、房喻,胡道道,李晓军 黄岑苷及其铜、锌配合物对超氧自由基德清除作用[J]生物化学杂志1991,7(6)：753-757
5、 张奉学,汪晓军,刘妮等黄苓苷对HBsAg和HBeAg的体外抑制作用【J】中西医结合肝病杂志200313(5)：267-269
6 卢春风,王丽敏,黄岑素和黄岑苷对四氯化碳所致肝脏损伤大鼠转氨酶的影响【J】黑龙江医药科学,2003,26(4)：50-51
7 薛洪源,侯艳宁,黄岑苷对异烟肼和利福平肝损伤小鼠的保护作用【J】解放军药学学报,2003,19(6)：414-417
8 Go Zh, Huang KX, Xu HB. Progress of studies in the bioac tivities of flavonoids extracted from scutellaria baicalensis [J].Chin pham J (in Chinese),1998,33(12):705-707
9 胡聪,韩聚强。黄芩苷对大鼠肝细胞凋亡的影响【J】中国中药杂志,2001,26(2)：124-127
10 唐云安,刘玉清,于国钦。肝损伤动物模型研究进展【J】卫生毒理学杂志,2002,16(4)：236-238
11 paronetto F, Popper H. Aggravation of hepatic lesions in mice by in vivo localization of immune complexes. Am J Pathol 1965,47:549-550
12 邱英峰,缪晓辉,蔡熊等。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【J】西北国防医学杂志,2004,25(5)：345
13 顾祖维。现代毒理学概论[M],北京,化学工业出版社2005：157
14 Vuppugalla R,Shah RB, Chimalakonda AP, Fisher CW, Mehvar R. Microsomal cytochrome P450 levels and activities of isolated rat livers perfused with albumin. Pharm Res 2003;20:81-88
15 Zhang LJ,Yu JP,Li D,Huang YH,Chen ZX,Wang XZ. Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats. Word J Gastroenterol 2004; 10:77-81
16 Barakat MM,EI-Kadi AOS,du Souich P.L-NAME prevents in vivo the inactivation but not the down-regulation of hepatic cytochrome P450 caused by an acute inflammatory reaction. Life Science 2001;69:1559-1571
17 Morgan ET,Ullrich V,Daiber A,Schmidt P,Takaya N,Shoun H, Mcjiff JC,Oyekan A,Hanke CJ,Campbell WB,Park CS,Kang JS,Yi HG,Cha YN,Mansuy D,Boucher JL.Cytochromes P450 and flavin monooxygenases-targets and sources of nitric oxide. Drug Metab Dispos 2001;29:1366-1376
18 钱江,何华.黄岑苷对过氧化脂质生成的抑制作用【J】.中国药科大学学报,1995,26(5)：308
19 蔡仙德,谭剑萍,穆维同等.黄岑苷对小鼠细胞免疫功能的影响【J】.南京铁道学院学报,1994,13(2)：443
20 蔡仙德,谭剑萍,穆维同等.黄岑苷对小鼠体液免疫的调节作用【J】.南京铁道学院学报,1995,14(3)：151
21 Orellana M, Rodrigo R, Varela N, et al.Relationship betw een in vivo chlo rzox azone hydrox y.ation, hepat ic cytochr ome P4502E1 content and liver injur y in obese no nalco holic fatty liver disease patients[J]. H epato 1 Res,2005,21(2):1541-1546.
22 胡之璧,贺丽虹,赵淑娟.细胞色素P450研究进展(J),江苏中药,2006(27)10：81-84
23 薛永志,章国良,步秀云,等.选择性iNOS抑制剂氨基胍减缓小鼠BCG免疫性肝损伤造成的P450降低[J].基础医学与临床,2004,24(8)：385-387.
24 Liz, ShiHY, Zhang M. Targeted expression of maspin in tumor vasculatures induces endot helial cell apoptosis. Onco2gene,2005,24:2008-2019
25 Amet Y,Gautier EP,Berthouf,et al.Adaptation to chronic ethanoladministration emphasized by fatty acid hydroxylations in rat liver and kidney microsomes [J].Eur J Nutr,2000,39 (6):270-276
26 Liebe CS.Alcoholic fatty liver:its pathogenesis and mechanism of progression to inflammation and fibrosis [J],Alcohol,2004,34 (1):9-19
27 黄林清,杨志勇.肝细胞色素P450与药物代谢的研究进展(J).中国药房,2001,(12)6：372-373
28 Zhang M, Volpert O, Shi YH, et al. Maspin is an angiogenesis inhibitor.Nat Med, 2000,6:196-199.
[1]Liebe CS.Alcoholic fatty liver:its pathogenesis and mechanism of progression to inflammation and fibrosis [J],Alcohol,2004,34 (1):9-19
[2]胡之璧,贺丽虹,赵淑娟.细胞色素P450 研究进展(J),江苏中医药,2006,(27)10：81-84
[3]郭与喻,汪晖.人细胞色素P450 同工酶探针底物特异性的研究进展(J)中国药理学报,2007,23(7)：851-854
[4]Bolthm, Roos PH, Thier.The cytochrome P450 isoenzyme CYP2E1 in the bioloogical processing of industrial chemicals:consequences for occupational and environmental medicine [J] Int Arch Occup Environ Health,2003,76 (3):174-185
[5]Badger TM, Ronis MJ, Seitz HK, et al.Alcohol metabolism:role in toxicity and carcinogenesis [J]1Alcohol Clin Exp Res,2003,27 (2):336-347
[6]Woodcroft KJ,Hafner MS,Novak RF.Insulin signaling in the tran-scriptional and posttranscriptional regulation of CYP2E1 expression [J] 1 Hepatology,2002,35 (2):263-273
[7]Woodcrof KJ,,Novak RF.Insulin effects on CYP2E1,2B,3A,and 4A expression in primary cultured rat hepatocytes [J] 1 Chem Biol In-teract,1997,107 (12):75-91
[8]Amet Y,Gautier EP,Berthouf,et a 1.Adaptation to chronic ethanoladministration emphasized by fatty acid hydroxylations in rat liver and kidney microsomes [J].Eur J Nutr,2000,39 (6):270-276
[9]Gemmass,Vichis,Testaie.Individual susceptibility and alcohol effects:Bioch-emical and genetic aspects [J].Ann Ist Super Sanita,2006,42 (1):8-16
[10]Zhuge J, Luo Y, YuYN1Heterologous expression of human cytochrome p4502Elin HepG2 cell line [J].World J Gastroenter2003,9 (12):2732-2736
[11]刘克洲.酒精性肝病发病机理的研究进展(J).中华消化杂志,2002,22(4)：230-232
[12]黄林清,杨志勇.肝细胞色素P450与药物代谢的研究进展(J).中国药房,2001,(12)6：372-373
[13]Cao Q, Makkm, Lieber CS. Cytochrome P4502Elprimes macrophages to increase TNF□alpha production in response to lipopolysaccharide. Am J Physio 1 GastrointestLiver Physiol,2005,289(1):G95-107.
[14]Orellana M, Rodrigo R, Varela N, et al.Relationship betw een in vivo chlo rzox azone hydrox y.ation, hepat ic cytochr ome P450 2E1 content and liver injur y in obese no nalco holic fatty liver disease patients[J]. H epato 1 Res,2005,21(2): 1541-1546.
[15]薛永志,章国良,步秀云,等.选择性iNOS抑制剂氨基胍减缓小鼠BCG免疫性肝损伤造成的P450降低[J].基础医学与临床,2004,24(8)：385-387.
[16]Chen El, Yaters J R. Maspin and tumor metastasis. IUBMB Life,2006,58:25-29.
[17]Shi HY, Stafford LJ, Liu Z, et al. Maspin cont rols mammarytumor cell migration t hrough inhibiting Racl and Cdc42, but not t he RhoA GTPase. Cell Motil Cytoskeleton,2007, 64:338-346
[18]Zhang M, Volpert O, Shi YH, et al. Maspin is an angiogenesis inhibitor. Nat Med,2000,6:196-199.
[19]Liz, ShiHY, Zhang M. Targeted expression of maspin in tumor vasculatures induces endot helial cell apoptosis. Onco2gene,2005,24:2008-2019
2、杨晖,刘旭黄岑苷锌研究进展 昆明医学院学报2007,(3)：106-109
3、李延峰,梁绍荣,耿辉 黄岑苷金属配合物的研究进展【J】时珍国药,1999 10(2)：152-153
4、房喻,胡道道,李晓军 黄岑苷及其铜、锌配合物对超氧自由基德清除作用[J]生物化学杂志1991,7(6)：753-757
5、 张奉学,汪晓军,刘妮等黄苓苷对HBsAg和HBeAg的体外抑制作用【J】中西医结合肝病杂志200313(5)：267-269
6 卢春风,王丽敏,黄岑素和黄岑苷对四氯化碳所致肝脏损伤大鼠转氨酶的影响【J】黑龙江医药科学,2003,26(4)：50-51
7 薛洪源,侯艳宁,黄岑苷对异烟肼和利福平肝损伤小鼠的保护作用【J】解放军药学学报,2003,19(6)：414-417
8 Go Zh, Huang KX, Xu HB. Progress of studies in the bioac tivities of flavonoids extracted from scutellaria baicalensis [J].Chin pham J (in Chinese),1998,33(12):705-707
9 胡聪,韩聚强。黄芩苷对大鼠肝细胞凋亡的影响【J】中国中药杂志,2001,26(2)：124-127
10 唐云安,刘玉清,于国钦。肝损伤动物模型研究进展【J】卫生毒理学杂志,2002,16(4)：236-238
11 paronetto F, Popper H. Aggravation of hepatic lesions in mice by in vivo localization of immune complexes. Am J Pathol 1965,47:549-550
12 邱英峰,缪晓辉,蔡熊等。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【J】西北国防医学杂志,2004,25(5)：345
13 顾祖维。现代毒理学概论[M],北京,化学工业出版社2005：157
14 Vuppugalla R,Shah RB, Chimalakonda AP, Fisher CW, Mehvar R. Microsomal cytochrome P450 levels and activities of isolated rat livers perfused with albumin. Pharm Res 2003;20:81-88
15 Zhang LJ,Yu JP,Li D,Huang YH,Chen ZX,Wang XZ. Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats. Word J Gastroenterol 2004; 10:77-81
16 Barakat MM,EI-Kadi AOS,du Souich P.L-NAME prevents in vivo the inactivation but not the down-regulation of hepatic cytochrome P450 caused by an acute inflammatory reaction. Life Science 2001;69:1559-1571
17 Morgan ET,Ullrich V,Daiber A,Schmidt P,Takaya N,Shoun H, Mcjiff JC,Oyekan A,Hanke CJ,Campbell WB,Park CS,Kang JS,Yi HG,Cha YN,Mansuy D,Boucher JL.Cytochromes P450 and flavin monooxygenases-targets and sources of nitric oxide. Drug Metab Dispos 2001;29:1366-1376
18 钱江,何华.黄岑苷对过氧化脂质生成的抑制作用【J】.中国药科大学学报,1995,26(5)：308
19 蔡仙德,谭剑萍,穆维同等.黄岑苷对小鼠细胞免疫功能的影响【J】.南京铁道学院学报,1994,13(2)：443
20 蔡仙德,谭剑萍,穆维同等.黄岑苷对小鼠体液免疫的调节作用【J】.南京铁道学院学报,1995,14(3)：151
21 Orellana M, Rodrigo R, Varela N, et al.Relationship betw een in vivo chlo rzox azone hydrox y.ation, hepat ic cytochr ome P4502E1 content and liver injur y in obese no nalco holic fatty liver disease patients[J]. H epato 1 Res,2005,21(2):1541-1546.
22 胡之璧,贺丽虹,赵淑娟.细胞色素P450研究进展(J),江苏中药,2006(27)10：81-84
23 薛永志,章国良,步秀云,等.选择性iNOS抑制剂氨基胍减缓小鼠BCG免疫性肝损伤造成的P450降低[J].基础医学与临床,2004,24(8)：385-387.
24 Liz, ShiHY, Zhang M. Targeted expression of maspin in tumor vasculatures induces endot helial cell apoptosis. Onco2gene,2005,24:2008-2019
25 Amet Y,Gautier EP,Berthouf,et al.Adaptation to chronic ethanoladministration emphasized by fatty acid hydroxylations in rat liver and kidney microsomes [J].Eur J Nutr,2000,39 (6):270-276
26 Liebe CS.Alcoholic fatty liver:its pathogenesis and mechanism of progression to inflammation and fibrosis [J],Alcohol,2004,34 (1):9-19
27 黄林清,杨志勇.肝细胞色素P450与药物代谢的研究进展(J).中国药房,2001,(12)6：372-373
28 Zhang M, Volpert O, Shi YH, et al. Maspin is an angiogenesis inhibitor.Nat Med, 2000,6:196-199.
[1]Liebe CS.Alcoholic fatty liver:its pathogenesis and mechanism of progression to inflammation and fibrosis [J],Alcohol,2004,34 (1):9-19
[2]胡之璧,贺丽虹,赵淑娟.细胞色素P450 研究进展(J),江苏中医药,2006,(27)10：81-84
[3]郭与喻,汪晖.人细胞色素P450 同工酶探针底物特异性的研究进展(J)中国药理学报,2007,23(7)：851-854
[4]Bolthm, Roos PH, Thier.The cytochrome P450 isoenzyme CYP2E1 in the bioloogical processing of industrial chemicals:consequences for occupational and environmental medicine [J] Int Arch Occup Environ Health,2003,76 (3):174-185
[5]Badger TM, Ronis MJ, Seitz HK, et al.Alcohol metabolism:role in toxicity and carcinogenesis [J]1Alcohol Clin Exp Res,2003,27 (2):336-347
[6]Woodcroft KJ,Hafner MS,Novak RF.Insulin signaling in the tran-scriptional and posttranscriptional regulation of CYP2E1 expression [J] 1 Hepatology,2002,35 (2):263-273
[7]Woodcrof KJ,,Novak RF.Insulin effects on CYP2E1,2B,3A,and 4A expression in primary cultured rat hepatocytes [J] 1 Chem Biol In-teract,1997,107 (12):75-91
[8]Amet Y,Gautier EP,Berthouf,et a 1.Adaptation to chronic ethanoladministration emphasized by fatty acid hydroxylations in rat liver and kidney microsomes [J].Eur J Nutr,2000,39 (6):270-276
[9]Gemmass,Vichis,Testaie.Individual susceptibility and alcohol effects:Bioch-emical and genetic aspects [J].Ann Ist Super Sanita,2006,42 (1):8-16
[10]Zhuge J, Luo Y, YuYN1Heterologous expression of human cytochrome p4502Elin HepG2 cell line [J].World J Gastroenter2003,9 (12):2732-2736
[11]刘克洲.酒精性肝病发病机理的研究进展(J).中华消化杂志,2002,22(4)：230-232
[12]黄林清,杨志勇.肝细胞色素P450与药物代谢的研究进展(J).中国药房,2001,(12)6：372-373
[13]Cao Q, Makkm, Lieber CS. Cytochrome P4502Elprimes macrophages to increase TNF□alpha production in response to lipopolysaccharide. Am J Physio 1 GastrointestLiver Physiol,2005,289(1):G95-107.
[14]Orellana M, Rodrigo R, Varela N, et al.Relationship betw een in vivo chlo rzox azone hydrox y.ation, hepat ic cytochr ome P450 2E1 content and liver injur y in obese no nalco holic fatty liver disease patients[J]. H epato 1 Res,2005,21(2): 1541-1546.
[15]薛永志,章国良,步秀云,等.选择性iNOS抑制剂氨基胍减缓小鼠BCG免疫性肝损伤造成的P450降低[J].基础医学与临床,2004,24(8)：385-387.
[16]Chen El, Yaters J R. Maspin and tumor metastasis. IUBMB Life,2006,58:25-29.
[17]Shi HY, Stafford LJ, Liu Z, et al. Maspin cont rols mammarytumor cell migration t hrough inhibiting Racl and Cdc42, but not t he RhoA GTPase. Cell Motil Cytoskeleton,2007, 64:338-346
[18]Zhang M, Volpert O, Shi YH, et al. Maspin is an angiogenesis inhibitor. Nat Med,2000,6:196-199.
[19]Liz, ShiHY, Zhang M. Targeted expression of maspin in tumor vasculatures induces endot helial cell apoptosis. Onco2gene,2005,24:2008-2019