蜜炙远志降低胃粘膜损伤的机理研究
|
摘要
目的:阐明蜜炙远志降低胃粘膜损伤的生物学机理,拟从分子水平揭示中药炮制降低胃肠毒性的科学内涵,对指导临床安全合理使用远志具有实用价值和学术意义。
方法:应用药理学、胃肠电生理学、分子生物学等方法和手段,探索了生远志及其皂苷与蜜远志对胃粘膜损伤和保护机制。①采用甲基橙法考察了各受试药对小鼠胃排空的影响。②采用BL-420生物机能实验系统考察了对大鼠胃电生理的影响。③采用微循环实验观测了对小鼠胃粘膜血液循环的影响。④采用放免法测定了大鼠胃组织的P物质(SP)、生长抑素(SS)。⑤采用荧光分光光度法测定大鼠胃组织的前列腺素E_2(PGE_2);采用定磷法测定了大鼠胃组织钙离子三磷酸腺苷(Ca~(++)-ATPase)酶活性。⑥采用RT-PCR法考察了大鼠胃粘膜环氧合酶2(COX-2)、钙调素(CaM)、转化生长因子α(α-TGF)、肠三叶因子(ITF)表达水平。
结果:①生远志组与总皂苷组均能显著抑制小鼠胃排空(P＜0.01),并能显著抑制胃电快波、慢波频率(P＜0.01,P＜0.05);蜜远志则对小鼠胃排空、胃电快慢波均无显著影响。②生远志组能显著降低大鼠胃组织SP和SS的含量(P＜0.05);而蜜远志组与总皂苷则显著增加胃组织SP含量,降低SS含量,皂苷尤为显著(P＜0.05)。③生远志组能显著降低小鼠胃粘膜血液流速、使毛细血管收缩、减少单位面积的血管数、减少单位面积的每秒血流量(P＜0.05);蜜远志则能显著增加小鼠胃粘膜的血液流速、单位面积的每秒血流量(P＜0.05)。④生远志组及其皂苷组、蜜远志组有降低大鼠胃组织前列腺素E_2趋势,但无统计学意义。蜜远志组能显著增强大鼠胃粘膜COX-2的表达(P＜0.05),而生远志及其总皂苷对COX-2表达无明显影响。⑤生远志能显著降低大鼠胃组织Ca~(++)-ATP酶活力(P＜0.05),蜜远志及皂苷对其无显著影响。但蜜远志能显著增强钙调素基因的表达(P＜0.05),生远志与皂苷组对其影响不明显。⑥蜜远志能显著增强大鼠胃粘膜ITF的表达(P＜0.05),并能上调胃粘膜α-TGF基因表达,生远志对其无显著影响。
结论:生远志10g/kg及其总皂苷5g/kg均能导致胃粘膜损伤,而蜜炙远志10g/kg则能降低粘膜损伤,其机理可能与:①通过增加胃电快波频率,促使胃组织中SP物质释放,从而增加胃排空,进而防止胃粘膜损伤。②通过增加胃粘膜血液流速、扩张毛细血管平滑肌、提高每秒血流量,从而改善胃粘膜微循环,提高胃粘膜的抗损伤和修复能力。③通过增强胃组织Ca~(2+)-ATP酶活,消除细胞“钙超载”对粘膜的损害。④促进上皮细胞的分裂,加强对损伤部位的上皮整复。⑤增强胃粘膜肠三叶因子、α-TGF的表达,以增强对胃粘膜的保护和损伤修复等机制有关。
综上,蜜炙远志通过促进胃粘膜微循环、增加胃组织局部激素释放、促使相关酶活性、增强粘膜保护因子的表达等多层次、多途径来实现胃粘膜的保护及损伤修复。
Objective:Expound the biological mechanism of Radix Polygalae reducing the gastric mucosa damage by honey-fried,reveal the scientific connotation of traditional Chinese medicine reducing the stomach and intestines toxic by concoct in molecular level,It has great practical value and the academic significance of using Radix Polygalae reasonably and safely.
Methods:Application method of Pharmacology、stomach and intestines electrophysiology、molecular biology and so on.Explored the crude Radix P.and its saponins and the honey-stir-baked Radix P.to the gastric mucosa damage and the protection mechanism,We did the following researches:①use helianthin to research gastric emptying;②use BL-420 biologic analyzer to observe and record the electrophysiology and gastric microcirculation;③use RIA to determine SP、SS;④use fluorescence pectrophotometriy to determine PGE_2,test enzyme activity of Ca~(++)-ATPase by the colorimetric determination of phosphorus;⑤use RT-PCR to study the expression of COX-2、CaM、α-TGF and ITF.
Result:①Crude Radix P.and its saponins can obviously inhibit gastric motility(P＜0.01),remarkably both inhibit stomach's fast wave and slow wave(P＜0.01,P＜0.05),but Honey-stir-baked Radix P.can not;②Crude Radix P.can obviously decrease SP and SS(P＜0.05),Honey-stir-baked Radix P.can remarkably increase SP and decrease SS;③Crude Radix P.can remarkably cause gastric mucosal microcycle barrier(P＜0.05 );④Both Crude Radix P.and Honey-stir-baked Radix P. have not influence to PGE2;Honey-stir-baked Radix P.can enhance cox-2 expression (P＜0.05);⑤Crude Radix P.can obviously decrease the activity of Ca~(++)-ATPase in gastric tissue and Honey-stir-baked Radix P.enhance CaM expression(P＜0.05);⑥Honey-stir-baked Radix P.can enhanceα-TGF and ITF expression(P＜0.05).
Conclusion:Crude Radix P.(10g/kg) and its saponins(5g/kg) can damage the gastric mucosa,but Honey-stir-baked Radix P.can reduce this damage,The biological mechanism of Honey-stir-baked Radix P.reducing the gastric mucosal damage may related to the following factors:①Honey-stir-baked Radix P.can obviously increase SP of gastric tissue and improve the suppression of Crude Radix P. to stomach's fast wave,Thus improves the gastric motility;②Increase gastric mucosal blood flow,enhances the anti-damage and repair ability;③Improve the suppression of Crude Radix P.to the activity of Ca~(++)-ATPase in gastric tissue, eliminates the cell "calcium overload" to the mucous membrane harm;④The promotion epithelial cell's fission and strengthening restitution of damaging region;⑤Enhancea-TGF and ITF expression,increase the gastric mucosa protection and damage repair.
In brief,Honey-stir-baked Radix P.realize multi-level,the multi-ways to the gastric mucosa protection and the damage repair mainly through the promoting gastric mucosa microcycle,enhancing stomach organization local hormone release、urged the related enzyme activity、urged the gastric mucosal protection factor expression and so on.
方法:应用药理学、胃肠电生理学、分子生物学等方法和手段,探索了生远志及其皂苷与蜜远志对胃粘膜损伤和保护机制。①采用甲基橙法考察了各受试药对小鼠胃排空的影响。②采用BL-420生物机能实验系统考察了对大鼠胃电生理的影响。③采用微循环实验观测了对小鼠胃粘膜血液循环的影响。④采用放免法测定了大鼠胃组织的P物质(SP)、生长抑素(SS)。⑤采用荧光分光光度法测定大鼠胃组织的前列腺素E_2(PGE_2);采用定磷法测定了大鼠胃组织钙离子三磷酸腺苷(Ca~(++)-ATPase)酶活性。⑥采用RT-PCR法考察了大鼠胃粘膜环氧合酶2(COX-2)、钙调素(CaM)、转化生长因子α(α-TGF)、肠三叶因子(ITF)表达水平。
结果:①生远志组与总皂苷组均能显著抑制小鼠胃排空(P＜0.01),并能显著抑制胃电快波、慢波频率(P＜0.01,P＜0.05);蜜远志则对小鼠胃排空、胃电快慢波均无显著影响。②生远志组能显著降低大鼠胃组织SP和SS的含量(P＜0.05);而蜜远志组与总皂苷则显著增加胃组织SP含量,降低SS含量,皂苷尤为显著(P＜0.05)。③生远志组能显著降低小鼠胃粘膜血液流速、使毛细血管收缩、减少单位面积的血管数、减少单位面积的每秒血流量(P＜0.05);蜜远志则能显著增加小鼠胃粘膜的血液流速、单位面积的每秒血流量(P＜0.05)。④生远志组及其皂苷组、蜜远志组有降低大鼠胃组织前列腺素E_2趋势,但无统计学意义。蜜远志组能显著增强大鼠胃粘膜COX-2的表达(P＜0.05),而生远志及其总皂苷对COX-2表达无明显影响。⑤生远志能显著降低大鼠胃组织Ca~(++)-ATP酶活力(P＜0.05),蜜远志及皂苷对其无显著影响。但蜜远志能显著增强钙调素基因的表达(P＜0.05),生远志与皂苷组对其影响不明显。⑥蜜远志能显著增强大鼠胃粘膜ITF的表达(P＜0.05),并能上调胃粘膜α-TGF基因表达,生远志对其无显著影响。
结论:生远志10g/kg及其总皂苷5g/kg均能导致胃粘膜损伤,而蜜炙远志10g/kg则能降低粘膜损伤,其机理可能与:①通过增加胃电快波频率,促使胃组织中SP物质释放,从而增加胃排空,进而防止胃粘膜损伤。②通过增加胃粘膜血液流速、扩张毛细血管平滑肌、提高每秒血流量,从而改善胃粘膜微循环,提高胃粘膜的抗损伤和修复能力。③通过增强胃组织Ca~(2+)-ATP酶活,消除细胞“钙超载”对粘膜的损害。④促进上皮细胞的分裂,加强对损伤部位的上皮整复。⑤增强胃粘膜肠三叶因子、α-TGF的表达,以增强对胃粘膜的保护和损伤修复等机制有关。
综上,蜜炙远志通过促进胃粘膜微循环、增加胃组织局部激素释放、促使相关酶活性、增强粘膜保护因子的表达等多层次、多途径来实现胃粘膜的保护及损伤修复。
Objective:Expound the biological mechanism of Radix Polygalae reducing the gastric mucosa damage by honey-fried,reveal the scientific connotation of traditional Chinese medicine reducing the stomach and intestines toxic by concoct in molecular level,It has great practical value and the academic significance of using Radix Polygalae reasonably and safely.
Methods:Application method of Pharmacology、stomach and intestines electrophysiology、molecular biology and so on.Explored the crude Radix P.and its saponins and the honey-stir-baked Radix P.to the gastric mucosa damage and the protection mechanism,We did the following researches:①use helianthin to research gastric emptying;②use BL-420 biologic analyzer to observe and record the electrophysiology and gastric microcirculation;③use RIA to determine SP、SS;④use fluorescence pectrophotometriy to determine PGE_2,test enzyme activity of Ca~(++)-ATPase by the colorimetric determination of phosphorus;⑤use RT-PCR to study the expression of COX-2、CaM、α-TGF and ITF.
Result:①Crude Radix P.and its saponins can obviously inhibit gastric motility(P＜0.01),remarkably both inhibit stomach's fast wave and slow wave(P＜0.01,P＜0.05),but Honey-stir-baked Radix P.can not;②Crude Radix P.can obviously decrease SP and SS(P＜0.05),Honey-stir-baked Radix P.can remarkably increase SP and decrease SS;③Crude Radix P.can remarkably cause gastric mucosal microcycle barrier(P＜0.05 );④Both Crude Radix P.and Honey-stir-baked Radix P. have not influence to PGE2;Honey-stir-baked Radix P.can enhance cox-2 expression (P＜0.05);⑤Crude Radix P.can obviously decrease the activity of Ca~(++)-ATPase in gastric tissue and Honey-stir-baked Radix P.enhance CaM expression(P＜0.05);⑥Honey-stir-baked Radix P.can enhanceα-TGF and ITF expression(P＜0.05).
Conclusion:Crude Radix P.(10g/kg) and its saponins(5g/kg) can damage the gastric mucosa,but Honey-stir-baked Radix P.can reduce this damage,The biological mechanism of Honey-stir-baked Radix P.reducing the gastric mucosal damage may related to the following factors:①Honey-stir-baked Radix P.can obviously increase SP of gastric tissue and improve the suppression of Crude Radix P. to stomach's fast wave,Thus improves the gastric motility;②Increase gastric mucosal blood flow,enhances the anti-damage and repair ability;③Improve the suppression of Crude Radix P.to the activity of Ca~(++)-ATPase in gastric tissue, eliminates the cell "calcium overload" to the mucous membrane harm;④The promotion epithelial cell's fission and strengthening restitution of damaging region;⑤Enhancea-TGF and ITF expression,increase the gastric mucosa protection and damage repair.
In brief,Honey-stir-baked Radix P.realize multi-level,the multi-ways to the gastric mucosa protection and the damage repair mainly through the promoting gastric mucosa microcycle,enhancing stomach organization local hormone release、urged the related enzyme activity、urged the gastric mucosal protection factor expression and so on.
引文
[1]国家药典委员会.中华人民共和国药典2005版一部[M].北京:化学工业出版社,2005:107.
[2]顾观光,辑,杨鹏举,校注.神农本草经[M].北京:学苑出版社,2003:48.
[3]雷载权,张廷模.中华临床中药学[M].北京:人民卫生出版社,1998:1516.
[4]金世元,王琦.中药饮片炮制研究[M].北京:化学工业出版社,2004:349-352.
[5]王孝涛.历代中药炮制法汇典[M].南昌:江西科学技术出版社,1998:86-87.
[6]刘晓文,冯燕.远志的炮制沿革及现代研究[J].基层中药杂志,1996,10(2)17-18.
[7]李希,谢守德.远志不同炮制工艺比较[J].四川中药,2002,20(3)19-20.
[8]李光巍,杨吉奎,等.远志的炮制研究[J].黑龙江中医药,1994,5:41-42.
[9]陈达理,周立红.常用中药与不良反应[M].北京:军事医学科学出版社,1998:196.
[10]吴振扬.远志用甘草汤制法万不可减[J].中草药研究,1989,(3):15.
[11]杨树先,潘凤阳.远志致过敏反应1例[J].中国中药杂志,1993,18(4):246.
[12]刘时尹.远志过敏反应两例报告[J].中成药研究,1981,44.
[13]孙秀芳.远志引起过敏反应1例[J].新疆中医药,1997,15(1):38.
[14]王大观,杨淑芬.中药临床学[M].北京:人民卫生出版社,1998:276-277.
[15]王建,郭娟,武云.生远志与各炮制品的急性毒性及对胃粘膜损伤的影响[J].中国医学研究与临床,2005,3(2):5-6.
[16]刘贤武,吴晖晖,王建,等.远志及其不同蜜炙品的镇咳祛痰作用对比研究[J].时珍国医国药杂志,2006,17(12):2379-2380.
[17]郭娟,王建.生远志及炮制品对小鼠止咳化痰作用的影响[J].中药药理与临床,2003,19(4):29.
[18]王建,瞿燕,吴晖晖,等.远志及其不同蜜炙品的镇静安神作用对比研究[J].江苏中医药,2007,39(6):60-61.
[19]郭娟,王建,武云.远志不同炮制品对胃肠运动及消化功能的影响[J].中药药理与临床,2006,22(3、4):120-122.
[20]吴晖晖,王建,等.远志及其不同蜜炙品的急性毒性及其对胃肠运动的影响[J].四川中医,2006,24(11):16-17.
[21]田徽,武云,王建,等.生远志中总皂苷、生物碱、口山酮、脂肪油的急性毒性研究[J].中药药理与临床,2005,21(4):50-51.
[22]田徽.生远志的胃肠毒性物质基础及蜜炙减毒部分机理的研究[D].成都:成都中医药大学,2006.
[23]吴晖晖.蜜炙远志减毒存效的工艺优选及相关实验研究[D].成都:成都中医药大学,2007.
[24]肖崇厚.中药化学[M].上海:上海科学技术出版社,1997:387-388。
[25]李红芳,汪龙德,等.禁食对大鼠胃肠电活动的影响及神经机制[J].甘肃中医学院学报,1996,13(2):43.
[26]郭鹞,任东青.微循环血基础与实验方法[M].西安:第四军医大学出版社,2005:72-344.
[27]郭润康.略谈中药去心问题[J].中草药研究,1993,(6):39-44.
[28]张廷模.临床中药学[M].上海:上海科学技术出版社,2006:324.
[29]徐楚江.中药炮制学[M].上海:上海科学技术出版社,1991:7.
[30]李兆申,湛先保,许国铭.胃粘膜损伤与保护--基础与临床[M].上海:上海科学技术出版社,2004:209.
[31]Mersereau WA,Hinchey EJ.Relationship between the gastic myoelectric and mechanical activity in the genesis of ulcers in indomethacin-insulin treated rats[J].Dig Dis Sic,1988,33(2):200.
[32]Szurszewski JH.Electrical basis of gastrointestinal motility[M].In:Johnson LR(ed).Physiology of the Gatrointesinal Tract.NY:Raven Press,1981:1435.
[33]Geoghegan JG,Pappas TN.Central peptidergic control of gastric acid secretion[J].Gut,1997,40:164-166.
[34]Miller LJ.Gastrointestinal hormones and receptors.In Text of book of gastroenterology[M].Yamada T eds.Lippincott Wilkins,1991:35-66.
[35]路长林.神经肽基础与临床[M].上海:第二军医大学出版社,2000.
[36]朱文玉.胃肠肽的细胞保护作用[J].胃肠病学,1998,3:141-143.
[37]Rydning A,Lyng O,Aase S,et al.Substance P may attenuate gastric hyperemia by a mast cell-dependent mechanisms in the damaged gastric mucosa[J].Am J Physiol,1999,277(5Pt1):G1064-1073.
[38]Kawano S,Tsuji S.Role of mucosal blood flow:a conceptional review in gastric mucosal injury an protection[J].J Gastroenterol Hepatol,2000,15S:D1-6.
[39]Sato N,Kawano S,Taujl S,et al.Gastric blood flow in ulcer diseases[J].Stand J Gastroenterol,1995,30Suppl 208:14-20.
[40]Jacobson ED.Circulatory mechanisms of gastric mucosal damage and protection[J].Gastroenterology,1992,102:1788-1800.
[41]Yan CD,Gu L,Tian SP,et al.Effects of gastric mucosal blood flow on the role of adaptive cytoprotcetion of rat gastric mucosal[J].Sheng Li Hsueh Pao,1996,48(5):469-476.
[42]Lacy ER.Rapid epithelial restitution in the stomach:an updated perspective[J].Scand J Gastroenterol,1995,30Suppl 210:6-8.
[43]Paimela H,Goddard PJ,Silen W.Present views on restitution of Gastrointestinal epithelium[J].Dig Dis Sci,1995,40:2495-2496.
[44]Araki H,Ukawa H,Sugawa Y,et al.The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E_2 in rat stomach[J].Aliment Pharmacol Ther,2000,14(Suppl 1):116-124.
[45]Ko JK,Cho CH.Co-regulation of mucosal nitric oxide and prostaglandin in gastric adaptive cytoprotection[J].Inflamm Res,1999,48(9):471-478.
[46]Subbaramaiah K,Telang N,Ramonetti JT,et al.Transcription of cyclo-oxcygenase-2 is enhanced in transformed mammary epithelial cells[J].Cancer Res,1996,56(19):4424-4429.
[47]Jouzeau JY,Terlain B,Abid A,et al.Cyclo-oxygenase isoenzymes.How recent findings affect thinking about nonsteroidal anti-inflammatory drugs[J].Drugs,1997,53(4):563-582.
[48]江其生,胡德耀,肖南,等.失血性休克大鼠血管平滑肌细胞钙超载的三磷酸腺苷酶机制[J].中华创伤杂志,2003,19(6):337-339.
[49]邱云志,甘露,王红,等.钙调素及其对细胞增殖的影响研究现状[J].华北国防医药,2006,18(3):214-215.
[50]Szabo S,Kusstatscher S,Sakoulas G,et al.Growth factor:new 'endogenous drugs' for ulcer healing[J].Scand J Gastroenterol,1995,30Suppl 210:15-18.
[51]Calabro A,Milani S,Paladini,et al.Roles of growth factor in peptic ulcer healing[J].Dig Dis Sci,1995,40:2497-2504.
[52]Furukawa O,Okabe S.Effects of growth factors on acid-induced damage to rat gastric epithelial cells[J].J Clin Gastroenterol,1997,25 Suppl 1:S79-83.
[53]Furukawa O,Matsui H,Suzuki N,et al.Effects of transforming growth factor aipha and hepatocyte growth factor on acid-induced damage in rat gastric epithelial cells[J].Jpn J Pharmacol,1998,77:173-176.
[54]Palomino A,Hernandez-Bernal F,Haedo W,et al.A multicenter,randomized,double-blind clinical trial examing the effect of oral human recombinant epidermal growth factor on the healing of duodenal ulcers[J].Scand J Gastroenterol,2000,35:1016-1023.
[55]Babyatsky MW,de Beaumont M,Thim L,et al.Oral trefoil peptides protext against ethanal and indomethacin-induced gastric injury in rats[J].Gastroenterology,1996,110:489-497.
[56]Knoshida K,Taupin DR,Itoh H,et al.Distinct pathways of cell migration and antiapoptotic response to epithelial injury:structure-function analysis of human intestinal trefoil factor[J].Mol Cell Biol,2000,20(13):4680-4690.
[57]Chen YH,Lu Y,De Plaen IG,et al.Transcription factor NF-kappaB signals antianoikic function of trefoil factor3 on intestinal epithelial cells[J].Biochem Biophys Res Commun,2000,274(3):576-582.
[58] Kanai M, Mullen C,Podolsky DK. Intestinal trefoil factor induces activation of extracellular signal-regulated protein kinase in intestinal epithelial cells[J]. Proc Natl Acad Sci USA, 1998,95:178-182.
[59] Podolsky DK. Mechanisms of regulatory peptide action in the gastrointestinal tract:trefoil peptides[J]. J Gastroenterol, 2000,35 Supple 12:69-74.
[60] Taupin D, Wu DC, Jeon WK, et al. The trefoil gene family are coordinately expressed immedated early genes: EGF receptor an MAP kinase dependent interregulation[J]. J Clin Invest, 1999,103(9):R31-38.
[1]王孝涛.历代中药炮制法汇典(古代)[M].南昌:江西科学技术出版社,1998:81.
[2]刘晓文,冯燕.远志的炮制沿革及现代研究[J].基层中药杂志,1996,10(2):17-18.
[3]国家中医药管理局《中华本草》编委会.中华本草[M].上海:上海科学出版社,1998:1096.
[4]阴健.中药现代研究与临床应用[M].北京:学苑出版社,1994.
[5]李希,谢守德.远志不同炮制工艺比较[J].四川中药,2002,20(3):19-20.
[6]李光巍,杨吉奎,等.远志的炮制研究[J].黑龙江中医药,1994,5:41-42.
[7]刘惠茹,唐家福,肖辉.甘草炙远志不同炮制品远志皂甙的HPLC法测定[J].中国中医药科技,2000,7(4):235.
[8]王光志,万德光,刘友平,等.蜜远志质量控制方法的初步探讨[J].中成药,2007,29(2):241-243.
[9]李明贵.远志不同炮制方法的分析[J].海峡药学,2005,17(5):80-81
[10]夏厚林,董敏,盛燕,等.远志蜜炙前后化学成分的对比研究[J].时珍国医国药,2006,17(9):1620-1621.
[11]夏厚林,董敏,吴希,等.远志蜜炙前后HPLC指纹图谱对比研究[J].中草药,2006,37(11):1657-1659.
[12]何文彬.远志不同炮制方法的探讨[J].基层中药杂志,1994,8(1):8.
[13]王建,郭娟,武云.远志不同炮制品对胃肠运动及消化功能的影响[J].中药药理与临床,2006,22(3、4):120-121.
[14]王建,瞿燕,吴晖晖,等.远志及其不同蜜炙品的镇静安神作用对比研究[J].江苏中医药,2007,39(6):60-61.
[15]郭娟,王建.生远志及炮制品对小鼠止咳化痰作用[J].中药药理与临床,2003,19(4):29.
[16]刘贤武,吴晖晖,王建,等.远志及其不同蜜炙品的镇咳祛痰作用对比研究[J].时珍国医国药,2006,17(22):2379-2380.
[17]田徽,武云,王建,等.生远志中总皂苷、生物碱、口山酮、脂肪油 的急性毒性研究[J].中药药理与临床,2005,21(4):50-51.
[18]吴晖晖,王建,刘贤武等.远志及其不同蜜炙品的急性毒性及其对胃肠运动的影响[J].四川中医,2006,24(11):16-17.
[19]王建,吴晖晖,武云,等.生远志及其总皂苷与蜜远志的急性毒性比较研究[J].中药药理与临床,2004,(20)6:21.
[20]赵海平,王建,吴晖晖,等.生远志及其皂苷与蜜远志对大鼠胃组织中活性物质及酶活性的影响[J].时珍国医国药,2007,18(2):260-262.
[21]鲍荟竹,王建,吴晖晖,等.生远志及其皂苷与蜜远志对家兔离体肠平滑肌运动作用机制的实验研究[J].时珍国医国药,2007,18(2):257-259.
[22]彭汶铎,许石波.四种远志皂苷的镇咳和祛痰作用[J].中国药学杂志,1998,33(8):491.
[23]彭汶铎.远志皂苷H对离体平滑肌和心脏的作用[J].中国药学杂志,1999,34(4):241-243.
[24]金宝渊.远志生物碱成分的研究[J].中国中药杂志,1993(11):675.
[25]李聪,欧阳明安,汪汉卿.黄花远志黄花皂苷D的二维核磁共振谱研究[J].波谱学杂志,2000,17(1):41-46.
[26]]吴志军,欧阳明安,扬崇仁.黄花远志的齐墩果烷型三萜皂苷[J].云南植物研究,1999,21(3):357-363.
[27]Wan D G,Chen Y Z,Liu Y P.Dynamic changes of activeconstitutents of Polygala tenuifolia[J].J Chengdu UnivTradit Chin Med(成都中医药大学学报),1999,22(3):42-47.
[28]Liu Y P,Wan D G,Liu T,et al.Determination of saponinsin Polygalasp.from different area by spectrophotometer[J].J Chengdu Univ Tradit Chin Med(成都中医药大学学报),2000,23(2):46-47.
[29]Yang X D,Xu L Z,Yang S L.Advances in studies onxanthones and their pharmacological activities in plants of Polygala[J].Res Dev Nat Prod(天然产物研究与开发),2000,12:88-94.
[30]Jiang Y,Tu P F.Progress in studies on Polygala tenuifolia[J].Chin Tradit Herb Drugs(中草药),2001,32(8):759-761.
[31]Jin B Y,Piao Z Y.Studies on alkaloid constitutent of Polygala tenuifolia[J].China J Chin Mater Med(中国中药杂志),1993,18(11):675-677.
[32]Zhao Y S,Yan Z Y,Li Z L,et al.The determination of polysaccharides content in the different Polygala tenuifolia Willd resources from Shanxi[J].Lishizhen Med Mater MedRes(时珍国医国药),2005,16(9):867-868.
[33]Sun X F,Shi S Q,Yang G H.Studies on chemicalconstituents of fat oil of Polygala tenuifolia[J].J Chin MedMater(中药材),2000,23(1):35-36.
[34]Li P,Lu D,Liu J P,et al.Analysis of constituents of volatile oil from Polygala tenuifolia Willd by GC-MS[J].Special Wild Econom Anim Plant Res(特产研究),2003,(4):43-45.
[35]沈行良,Witt MR,Dekermendjian K,等.从远志中分离鉴定出1中多巴胺受体活性化合物.海南医学院学报,2004,10(3):133-135.
[36]Qiao J C,Yang Q,Determining the amount of metal element of Polygala tenuifoliain Mongolia[J].Chin Tradit MedMagaz(中国民族医药杂志),2001,7(4):32.
[37]聂淑琴.草药制剂的药理学特性(20):远志中天然前提药物的筛选[J].国外医学-中医中药分册,1996,18(6):39-40.
[38]张耀春,王立为.远志药理研究进展[J].国外医药植物药分册,2004;19(2):59-63.
[39]李光植,黄瑛,王琳.远志对D-半乳糖致衰小鼠红细胞中超氧化物歧化酶、肝组织谷胱甘肽过氧化物酶活性影响的实验研究[J].黑龙江医药科学,2000,23(1):4-5.
[40]马正立,汪丽亚.调心、补肾中药对大鼠基底核损伤所致乙酰胆碱酯酶变化的影响[J].老年学杂志,1993,13(5):301-303.
[41]王昌俊.益智灵的健脑作用[J].中成药,1993,(6):28.
[42]杨文明,韩明向,周宜轩,等.中药治疗老年痴呆的药理学基础(一)[J].安徽中医临床杂志,2001,13(5):316-318.
[43]陈勤,曹炎贵,张传惠.远志皂苷对淀粉样肽和鹅膏钧氨酸引起的胆碱系统功能降低的影响[J].药学学报,2002,37(12):913-917.
[44]Kim HM,Lee EH,Na HJ,et al.Effect of Polygalatenuifolia Root Extract on the Tumor Necrosis Factor-α-secretion from Mouse Astrocytes[J].Ethnopharmacol,1998,61:201-208.
[45]廖方正.脑力康对老年痴呆病的疗效观察[J].成都中医药大学学报,1996,19(1):20.
[46]徐光华.活血化瘀汤治疗中风78例[J].陕西中医,1994,(6):24.
[47]彭汶铎.远志皂苷的降压作用及其机制[J].中国药理学报,1999,20(7):639-642.
[48]张志军.远志对脂质代谢的影响[J].国外医学(中医中药分册),1996,18(2):36.
[49]段其芬.远志治疗急性乳腺炎[J].中国民间疗法,2001,9(8):45-46.
[50]刘德祥,殷学军,王河川,等.102种中药水溶性提取物的抗诱变性筛选[J].中国中药杂志,1990,15(10):41-46.
[51]马俊英,许建国,仙连生.苏木等15种中草药水提液体外对HL-60,Yac-1,K562,L929的细胞毒作用[J].天津医药,1990,1:41-42.
[52]张若明,李经才.解酒天然药物研究进展[J].化学合成,2002,10(4):285-291.
[53]黄晓舞,谢婷婷,王东晓,等.远志醇提物的抗抑郁作用[J].中国药物应用与监测,2007,4:22-25.
[54]赵蓉蓉.远志超声气雾液对癌变液细胞学的诊断[J].肿瘤,1995,15(1):57.
[2]顾观光,辑,杨鹏举,校注.神农本草经[M].北京:学苑出版社,2003:48.
[3]雷载权,张廷模.中华临床中药学[M].北京:人民卫生出版社,1998:1516.
[4]金世元,王琦.中药饮片炮制研究[M].北京:化学工业出版社,2004:349-352.
[5]王孝涛.历代中药炮制法汇典[M].南昌:江西科学技术出版社,1998:86-87.
[6]刘晓文,冯燕.远志的炮制沿革及现代研究[J].基层中药杂志,1996,10(2)17-18.
[7]李希,谢守德.远志不同炮制工艺比较[J].四川中药,2002,20(3)19-20.
[8]李光巍,杨吉奎,等.远志的炮制研究[J].黑龙江中医药,1994,5:41-42.
[9]陈达理,周立红.常用中药与不良反应[M].北京:军事医学科学出版社,1998:196.
[10]吴振扬.远志用甘草汤制法万不可减[J].中草药研究,1989,(3):15.
[11]杨树先,潘凤阳.远志致过敏反应1例[J].中国中药杂志,1993,18(4):246.
[12]刘时尹.远志过敏反应两例报告[J].中成药研究,1981,44.
[13]孙秀芳.远志引起过敏反应1例[J].新疆中医药,1997,15(1):38.
[14]王大观,杨淑芬.中药临床学[M].北京:人民卫生出版社,1998:276-277.
[15]王建,郭娟,武云.生远志与各炮制品的急性毒性及对胃粘膜损伤的影响[J].中国医学研究与临床,2005,3(2):5-6.
[16]刘贤武,吴晖晖,王建,等.远志及其不同蜜炙品的镇咳祛痰作用对比研究[J].时珍国医国药杂志,2006,17(12):2379-2380.
[17]郭娟,王建.生远志及炮制品对小鼠止咳化痰作用的影响[J].中药药理与临床,2003,19(4):29.
[18]王建,瞿燕,吴晖晖,等.远志及其不同蜜炙品的镇静安神作用对比研究[J].江苏中医药,2007,39(6):60-61.
[19]郭娟,王建,武云.远志不同炮制品对胃肠运动及消化功能的影响[J].中药药理与临床,2006,22(3、4):120-122.
[20]吴晖晖,王建,等.远志及其不同蜜炙品的急性毒性及其对胃肠运动的影响[J].四川中医,2006,24(11):16-17.
[21]田徽,武云,王建,等.生远志中总皂苷、生物碱、口山酮、脂肪油的急性毒性研究[J].中药药理与临床,2005,21(4):50-51.
[22]田徽.生远志的胃肠毒性物质基础及蜜炙减毒部分机理的研究[D].成都:成都中医药大学,2006.
[23]吴晖晖.蜜炙远志减毒存效的工艺优选及相关实验研究[D].成都:成都中医药大学,2007.
[24]肖崇厚.中药化学[M].上海:上海科学技术出版社,1997:387-388。
[25]李红芳,汪龙德,等.禁食对大鼠胃肠电活动的影响及神经机制[J].甘肃中医学院学报,1996,13(2):43.
[26]郭鹞,任东青.微循环血基础与实验方法[M].西安:第四军医大学出版社,2005:72-344.
[27]郭润康.略谈中药去心问题[J].中草药研究,1993,(6):39-44.
[28]张廷模.临床中药学[M].上海:上海科学技术出版社,2006:324.
[29]徐楚江.中药炮制学[M].上海:上海科学技术出版社,1991:7.
[30]李兆申,湛先保,许国铭.胃粘膜损伤与保护--基础与临床[M].上海:上海科学技术出版社,2004:209.
[31]Mersereau WA,Hinchey EJ.Relationship between the gastic myoelectric and mechanical activity in the genesis of ulcers in indomethacin-insulin treated rats[J].Dig Dis Sic,1988,33(2):200.
[32]Szurszewski JH.Electrical basis of gastrointestinal motility[M].In:Johnson LR(ed).Physiology of the Gatrointesinal Tract.NY:Raven Press,1981:1435.
[33]Geoghegan JG,Pappas TN.Central peptidergic control of gastric acid secretion[J].Gut,1997,40:164-166.
[34]Miller LJ.Gastrointestinal hormones and receptors.In Text of book of gastroenterology[M].Yamada T eds.Lippincott Wilkins,1991:35-66.
[35]路长林.神经肽基础与临床[M].上海:第二军医大学出版社,2000.
[36]朱文玉.胃肠肽的细胞保护作用[J].胃肠病学,1998,3:141-143.
[37]Rydning A,Lyng O,Aase S,et al.Substance P may attenuate gastric hyperemia by a mast cell-dependent mechanisms in the damaged gastric mucosa[J].Am J Physiol,1999,277(5Pt1):G1064-1073.
[38]Kawano S,Tsuji S.Role of mucosal blood flow:a conceptional review in gastric mucosal injury an protection[J].J Gastroenterol Hepatol,2000,15S:D1-6.
[39]Sato N,Kawano S,Taujl S,et al.Gastric blood flow in ulcer diseases[J].Stand J Gastroenterol,1995,30Suppl 208:14-20.
[40]Jacobson ED.Circulatory mechanisms of gastric mucosal damage and protection[J].Gastroenterology,1992,102:1788-1800.
[41]Yan CD,Gu L,Tian SP,et al.Effects of gastric mucosal blood flow on the role of adaptive cytoprotcetion of rat gastric mucosal[J].Sheng Li Hsueh Pao,1996,48(5):469-476.
[42]Lacy ER.Rapid epithelial restitution in the stomach:an updated perspective[J].Scand J Gastroenterol,1995,30Suppl 210:6-8.
[43]Paimela H,Goddard PJ,Silen W.Present views on restitution of Gastrointestinal epithelium[J].Dig Dis Sci,1995,40:2495-2496.
[44]Araki H,Ukawa H,Sugawa Y,et al.The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E_2 in rat stomach[J].Aliment Pharmacol Ther,2000,14(Suppl 1):116-124.
[45]Ko JK,Cho CH.Co-regulation of mucosal nitric oxide and prostaglandin in gastric adaptive cytoprotection[J].Inflamm Res,1999,48(9):471-478.
[46]Subbaramaiah K,Telang N,Ramonetti JT,et al.Transcription of cyclo-oxcygenase-2 is enhanced in transformed mammary epithelial cells[J].Cancer Res,1996,56(19):4424-4429.
[47]Jouzeau JY,Terlain B,Abid A,et al.Cyclo-oxygenase isoenzymes.How recent findings affect thinking about nonsteroidal anti-inflammatory drugs[J].Drugs,1997,53(4):563-582.
[48]江其生,胡德耀,肖南,等.失血性休克大鼠血管平滑肌细胞钙超载的三磷酸腺苷酶机制[J].中华创伤杂志,2003,19(6):337-339.
[49]邱云志,甘露,王红,等.钙调素及其对细胞增殖的影响研究现状[J].华北国防医药,2006,18(3):214-215.
[50]Szabo S,Kusstatscher S,Sakoulas G,et al.Growth factor:new 'endogenous drugs' for ulcer healing[J].Scand J Gastroenterol,1995,30Suppl 210:15-18.
[51]Calabro A,Milani S,Paladini,et al.Roles of growth factor in peptic ulcer healing[J].Dig Dis Sci,1995,40:2497-2504.
[52]Furukawa O,Okabe S.Effects of growth factors on acid-induced damage to rat gastric epithelial cells[J].J Clin Gastroenterol,1997,25 Suppl 1:S79-83.
[53]Furukawa O,Matsui H,Suzuki N,et al.Effects of transforming growth factor aipha and hepatocyte growth factor on acid-induced damage in rat gastric epithelial cells[J].Jpn J Pharmacol,1998,77:173-176.
[54]Palomino A,Hernandez-Bernal F,Haedo W,et al.A multicenter,randomized,double-blind clinical trial examing the effect of oral human recombinant epidermal growth factor on the healing of duodenal ulcers[J].Scand J Gastroenterol,2000,35:1016-1023.
[55]Babyatsky MW,de Beaumont M,Thim L,et al.Oral trefoil peptides protext against ethanal and indomethacin-induced gastric injury in rats[J].Gastroenterology,1996,110:489-497.
[56]Knoshida K,Taupin DR,Itoh H,et al.Distinct pathways of cell migration and antiapoptotic response to epithelial injury:structure-function analysis of human intestinal trefoil factor[J].Mol Cell Biol,2000,20(13):4680-4690.
[57]Chen YH,Lu Y,De Plaen IG,et al.Transcription factor NF-kappaB signals antianoikic function of trefoil factor3 on intestinal epithelial cells[J].Biochem Biophys Res Commun,2000,274(3):576-582.
[58] Kanai M, Mullen C,Podolsky DK. Intestinal trefoil factor induces activation of extracellular signal-regulated protein kinase in intestinal epithelial cells[J]. Proc Natl Acad Sci USA, 1998,95:178-182.
[59] Podolsky DK. Mechanisms of regulatory peptide action in the gastrointestinal tract:trefoil peptides[J]. J Gastroenterol, 2000,35 Supple 12:69-74.
[60] Taupin D, Wu DC, Jeon WK, et al. The trefoil gene family are coordinately expressed immedated early genes: EGF receptor an MAP kinase dependent interregulation[J]. J Clin Invest, 1999,103(9):R31-38.
[1]王孝涛.历代中药炮制法汇典(古代)[M].南昌:江西科学技术出版社,1998:81.
[2]刘晓文,冯燕.远志的炮制沿革及现代研究[J].基层中药杂志,1996,10(2):17-18.
[3]国家中医药管理局《中华本草》编委会.中华本草[M].上海:上海科学出版社,1998:1096.
[4]阴健.中药现代研究与临床应用[M].北京:学苑出版社,1994.
[5]李希,谢守德.远志不同炮制工艺比较[J].四川中药,2002,20(3):19-20.
[6]李光巍,杨吉奎,等.远志的炮制研究[J].黑龙江中医药,1994,5:41-42.
[7]刘惠茹,唐家福,肖辉.甘草炙远志不同炮制品远志皂甙的HPLC法测定[J].中国中医药科技,2000,7(4):235.
[8]王光志,万德光,刘友平,等.蜜远志质量控制方法的初步探讨[J].中成药,2007,29(2):241-243.
[9]李明贵.远志不同炮制方法的分析[J].海峡药学,2005,17(5):80-81
[10]夏厚林,董敏,盛燕,等.远志蜜炙前后化学成分的对比研究[J].时珍国医国药,2006,17(9):1620-1621.
[11]夏厚林,董敏,吴希,等.远志蜜炙前后HPLC指纹图谱对比研究[J].中草药,2006,37(11):1657-1659.
[12]何文彬.远志不同炮制方法的探讨[J].基层中药杂志,1994,8(1):8.
[13]王建,郭娟,武云.远志不同炮制品对胃肠运动及消化功能的影响[J].中药药理与临床,2006,22(3、4):120-121.
[14]王建,瞿燕,吴晖晖,等.远志及其不同蜜炙品的镇静安神作用对比研究[J].江苏中医药,2007,39(6):60-61.
[15]郭娟,王建.生远志及炮制品对小鼠止咳化痰作用[J].中药药理与临床,2003,19(4):29.
[16]刘贤武,吴晖晖,王建,等.远志及其不同蜜炙品的镇咳祛痰作用对比研究[J].时珍国医国药,2006,17(22):2379-2380.
[17]田徽,武云,王建,等.生远志中总皂苷、生物碱、口山酮、脂肪油 的急性毒性研究[J].中药药理与临床,2005,21(4):50-51.
[18]吴晖晖,王建,刘贤武等.远志及其不同蜜炙品的急性毒性及其对胃肠运动的影响[J].四川中医,2006,24(11):16-17.
[19]王建,吴晖晖,武云,等.生远志及其总皂苷与蜜远志的急性毒性比较研究[J].中药药理与临床,2004,(20)6:21.
[20]赵海平,王建,吴晖晖,等.生远志及其皂苷与蜜远志对大鼠胃组织中活性物质及酶活性的影响[J].时珍国医国药,2007,18(2):260-262.
[21]鲍荟竹,王建,吴晖晖,等.生远志及其皂苷与蜜远志对家兔离体肠平滑肌运动作用机制的实验研究[J].时珍国医国药,2007,18(2):257-259.
[22]彭汶铎,许石波.四种远志皂苷的镇咳和祛痰作用[J].中国药学杂志,1998,33(8):491.
[23]彭汶铎.远志皂苷H对离体平滑肌和心脏的作用[J].中国药学杂志,1999,34(4):241-243.
[24]金宝渊.远志生物碱成分的研究[J].中国中药杂志,1993(11):675.
[25]李聪,欧阳明安,汪汉卿.黄花远志黄花皂苷D的二维核磁共振谱研究[J].波谱学杂志,2000,17(1):41-46.
[26]]吴志军,欧阳明安,扬崇仁.黄花远志的齐墩果烷型三萜皂苷[J].云南植物研究,1999,21(3):357-363.
[27]Wan D G,Chen Y Z,Liu Y P.Dynamic changes of activeconstitutents of Polygala tenuifolia[J].J Chengdu UnivTradit Chin Med(成都中医药大学学报),1999,22(3):42-47.
[28]Liu Y P,Wan D G,Liu T,et al.Determination of saponinsin Polygalasp.from different area by spectrophotometer[J].J Chengdu Univ Tradit Chin Med(成都中医药大学学报),2000,23(2):46-47.
[29]Yang X D,Xu L Z,Yang S L.Advances in studies onxanthones and their pharmacological activities in plants of Polygala[J].Res Dev Nat Prod(天然产物研究与开发),2000,12:88-94.
[30]Jiang Y,Tu P F.Progress in studies on Polygala tenuifolia[J].Chin Tradit Herb Drugs(中草药),2001,32(8):759-761.
[31]Jin B Y,Piao Z Y.Studies on alkaloid constitutent of Polygala tenuifolia[J].China J Chin Mater Med(中国中药杂志),1993,18(11):675-677.
[32]Zhao Y S,Yan Z Y,Li Z L,et al.The determination of polysaccharides content in the different Polygala tenuifolia Willd resources from Shanxi[J].Lishizhen Med Mater MedRes(时珍国医国药),2005,16(9):867-868.
[33]Sun X F,Shi S Q,Yang G H.Studies on chemicalconstituents of fat oil of Polygala tenuifolia[J].J Chin MedMater(中药材),2000,23(1):35-36.
[34]Li P,Lu D,Liu J P,et al.Analysis of constituents of volatile oil from Polygala tenuifolia Willd by GC-MS[J].Special Wild Econom Anim Plant Res(特产研究),2003,(4):43-45.
[35]沈行良,Witt MR,Dekermendjian K,等.从远志中分离鉴定出1中多巴胺受体活性化合物.海南医学院学报,2004,10(3):133-135.
[36]Qiao J C,Yang Q,Determining the amount of metal element of Polygala tenuifoliain Mongolia[J].Chin Tradit MedMagaz(中国民族医药杂志),2001,7(4):32.
[37]聂淑琴.草药制剂的药理学特性(20):远志中天然前提药物的筛选[J].国外医学-中医中药分册,1996,18(6):39-40.
[38]张耀春,王立为.远志药理研究进展[J].国外医药植物药分册,2004;19(2):59-63.
[39]李光植,黄瑛,王琳.远志对D-半乳糖致衰小鼠红细胞中超氧化物歧化酶、肝组织谷胱甘肽过氧化物酶活性影响的实验研究[J].黑龙江医药科学,2000,23(1):4-5.
[40]马正立,汪丽亚.调心、补肾中药对大鼠基底核损伤所致乙酰胆碱酯酶变化的影响[J].老年学杂志,1993,13(5):301-303.
[41]王昌俊.益智灵的健脑作用[J].中成药,1993,(6):28.
[42]杨文明,韩明向,周宜轩,等.中药治疗老年痴呆的药理学基础(一)[J].安徽中医临床杂志,2001,13(5):316-318.
[43]陈勤,曹炎贵,张传惠.远志皂苷对淀粉样肽和鹅膏钧氨酸引起的胆碱系统功能降低的影响[J].药学学报,2002,37(12):913-917.
[44]Kim HM,Lee EH,Na HJ,et al.Effect of Polygalatenuifolia Root Extract on the Tumor Necrosis Factor-α-secretion from Mouse Astrocytes[J].Ethnopharmacol,1998,61:201-208.
[45]廖方正.脑力康对老年痴呆病的疗效观察[J].成都中医药大学学报,1996,19(1):20.
[46]徐光华.活血化瘀汤治疗中风78例[J].陕西中医,1994,(6):24.
[47]彭汶铎.远志皂苷的降压作用及其机制[J].中国药理学报,1999,20(7):639-642.
[48]张志军.远志对脂质代谢的影响[J].国外医学(中医中药分册),1996,18(2):36.
[49]段其芬.远志治疗急性乳腺炎[J].中国民间疗法,2001,9(8):45-46.
[50]刘德祥,殷学军,王河川,等.102种中药水溶性提取物的抗诱变性筛选[J].中国中药杂志,1990,15(10):41-46.
[51]马俊英,许建国,仙连生.苏木等15种中草药水提液体外对HL-60,Yac-1,K562,L929的细胞毒作用[J].天津医药,1990,1:41-42.
[52]张若明,李经才.解酒天然药物研究进展[J].化学合成,2002,10(4):285-291.
[53]黄晓舞,谢婷婷,王东晓,等.远志醇提物的抗抑郁作用[J].中国药物应用与监测,2007,4:22-25.
[54]赵蓉蓉.远志超声气雾液对癌变液细胞学的诊断[J].肿瘤,1995,15(1):57.