蓝靛果提取物抗溃疡活性部位筛选及药理探讨
摘要
目的:研究蓝靛果提取物抗实验性胃溃疡的有效活性部位、及其药理作用和机理探讨
方法:本课题采用无水乙醇实验性胃溃疡模型、利血平实验性胃溃疡模型对蓝靛果的总提取物、正丁醇萃取物、乙酸乙酯萃取物、萃取物后剩余物进行筛选。并对其中的有效部位乙酸乙酯萃取物进一步做了乙酸型实验性胃溃疡模型、利血平实验性胃溃疡模型、消炎痛实验性胃溃疡模型、无水乙醇实验性胃溃疡模型的药理研究。并测量了血清及胃粘膜中NO、MDA含量,及测定了SOD的活性,检测了血清中胃幽门螺旋杆菌抗体的含量。观察了蓝靛果乙酸乙酯萃取物(EELC)对胃溃疡的防治作用,而且对其抗溃疡机理进行了探讨。
实验结果:
蓝靛果乙酸乙酯萃取物能明显促进乙酸型实验性胃溃疡的愈合。其2g/kg、4g/kg两个剂量组的溃疡指数与常水对照组相比有明显的差异(p<0.05、p<0.01)。溃疡抑制率为53.6%和84.2%。但与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/kg、4g/kg)三个剂量组能明显减轻无水乙醇所致的小鼠胃粘膜损伤,与常水对照组相比有显著性差异(p<0.05、p<0.01、p<0.01)。其溃疡抑制率分别为49.05%、58.49%、67.92%。但与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/k、4g/kg)三个剂量组能明显减轻消炎痛所致的实验性胃溃疡胃粘膜损伤。与常水对照组相比有明显的差异(p<0.05、p<0.01、p<0.01),其溃疡抑制率为24.4%、35.6%、64.4%。与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/kg、4g/kg)三个剂量组能对抗小鼠利血平所致的胃粘膜损伤。与常水对照组相比有明显差异(p<0.05、p<0.01、
OBJECTTVE:In order to filt effectual portion extraction of Lonicera caerulea L Var edulis turcz Ex Herd(LC) on experimental gastric ulcer in rats and investigate the preventive and curative action of Ethyl acetate extraction of Lonicera Caerulea L Var edulis Turcz Ex herd(EELC) on experimental gastric ulcer in rats. METHOD:The lonicera caeruler L Var edulis turcz ex Herd(LC)was batch extracted using the grain alcohol ethyl acetate and n-butanol the preventive and curative action of grain alcohol extraction of LC,ethyl acetate extraction of LC,n-batanol extraction of Lc,remainders on two kinds of gastric ulcer models including reserpine and grain alcohol induced ulcers were investigated.EELC on four kinds of gastric ulcer models including acetic acid, reserpine , indomethacin and 100%EtoH induced gastric ulcer was observed.Some biochemical parameters were measured,such as the amount of antibody of gastric pylorus twist bacilli in serum. The SOD activity and MDA, NO amount of serum and gastric mucosal in rats of acetic induced gastric ulcer models were measured.RESULT:Ethyl acetate extraction of lonicera Caerulea L var edulis turcz Ex herd (EELC) could markedly stimulate the healing of acetic acid induced gastric ulcer.The two dose groups (2g/kg, 4g/kg)were all significal different from that of control group
(p<0.05 ^ p<0.01) and the gastric ulcer rates of inhibition were 53.6% and 84.2respectively,but had no significantly differently from the Cimetidine group(2g/kg).EELC could markedly reduce the gastric ulcer of grain alcohol induced (p<0.05^ p<0.0k p<0.01).The gastric ulcer rates of inhibition of the three dose group(lg/kg, 2g/kg^ 4g/kg)were49.05%,58.49% and 67.92%.Its were all significantly different from that of control group (p<0.05^p<0.0kp<0.01), but had no significantly differently from the cimetidine group (2g/kg).EELC (lg/kg^2g/kg^4g/kg) could inhibit the formation of indomethacin induced gastric ulcer (p<0.05^ p<0.01 ^ p<0.01).The gastric ulcer rates of inhibition of three dose groups were 24.4%^ 35.6% and 64.4%(p<0.05 N p<0.01 ^ p<0.01) ,and its were significantly differently from the control group,but had no significantly from the cimetidine group (0.2g/kg).EELC (lg/kg ? 2g/kg) could inhibit reserpine induced the gastric ulcer ,and were significantly from that of control group(p<0.01 ^ p<0.01).the gastric ulcer rates of inhibition of the two dose groups were 40.7% and 61.1% ., 79.6%, but had no significantly differently from the cimetidine group (2g/kg).EE1C could significal reduce the amount of antibody of gastric pylorus twist bacilli (p<0.05^ p<0.01).Its were all significantly different from that of the control group.(p<0.05^ p<0.01).Its had differently from cimetidine control (2g/kg).EELC (4g/kg) markedly increased the activity of SOD in gastric ulcer juicejt was significantly differently from that of the control group (p<0.05),but it little dose (2g/kg) had no effect on SOD activity in gastric mucosal juice .EELC had no effect on SOD activity in serum.EELC had no effect on the MDA amount of serum and mucosal juice .EELC had no effect on the NO content of serum and gastric mucosal juice. CONCLUSIONrEELC is the effectual portion of LC in the using of preventive and curative action on experiment gastric ulcer in rats.The results indicate that the EELC had preventive and curative effect against chronic and some acute gastric ulcer .Its mechanisms of the anti-ulcer action maybe associated with its ability to enhance the gastric mucosal defending,weaken the attacking factors and accelerate the
regeneration and repair of injured mucosal by means of improving the mucosal blood circulation resisting the free radicals > inhibiting the lipid peroxidation ^ stimulating the synthesis of DNA> RNA and protein > inhibiting the reproducer of bacillus.
方法:本课题采用无水乙醇实验性胃溃疡模型、利血平实验性胃溃疡模型对蓝靛果的总提取物、正丁醇萃取物、乙酸乙酯萃取物、萃取物后剩余物进行筛选。并对其中的有效部位乙酸乙酯萃取物进一步做了乙酸型实验性胃溃疡模型、利血平实验性胃溃疡模型、消炎痛实验性胃溃疡模型、无水乙醇实验性胃溃疡模型的药理研究。并测量了血清及胃粘膜中NO、MDA含量,及测定了SOD的活性,检测了血清中胃幽门螺旋杆菌抗体的含量。观察了蓝靛果乙酸乙酯萃取物(EELC)对胃溃疡的防治作用,而且对其抗溃疡机理进行了探讨。
实验结果:
蓝靛果乙酸乙酯萃取物能明显促进乙酸型实验性胃溃疡的愈合。其2g/kg、4g/kg两个剂量组的溃疡指数与常水对照组相比有明显的差异(p<0.05、p<0.01)。溃疡抑制率为53.6%和84.2%。但与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/kg、4g/kg)三个剂量组能明显减轻无水乙醇所致的小鼠胃粘膜损伤,与常水对照组相比有显著性差异(p<0.05、p<0.01、p<0.01)。其溃疡抑制率分别为49.05%、58.49%、67.92%。但与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/k、4g/kg)三个剂量组能明显减轻消炎痛所致的实验性胃溃疡胃粘膜损伤。与常水对照组相比有明显的差异(p<0.05、p<0.01、p<0.01),其溃疡抑制率为24.4%、35.6%、64.4%。与西咪替丁阳性对照组相比无明显差异。
蓝靛果乙酸乙酯萃取物(1g/kg、2g/kg、4g/kg)三个剂量组能对抗小鼠利血平所致的胃粘膜损伤。与常水对照组相比有明显差异(p<0.05、p<0.01、
OBJECTTVE:In order to filt effectual portion extraction of Lonicera caerulea L Var edulis turcz Ex Herd(LC) on experimental gastric ulcer in rats and investigate the preventive and curative action of Ethyl acetate extraction of Lonicera Caerulea L Var edulis Turcz Ex herd(EELC) on experimental gastric ulcer in rats. METHOD:The lonicera caeruler L Var edulis turcz ex Herd(LC)was batch extracted using the grain alcohol ethyl acetate and n-butanol the preventive and curative action of grain alcohol extraction of LC,ethyl acetate extraction of LC,n-batanol extraction of Lc,remainders on two kinds of gastric ulcer models including reserpine and grain alcohol induced ulcers were investigated.EELC on four kinds of gastric ulcer models including acetic acid, reserpine , indomethacin and 100%EtoH induced gastric ulcer was observed.Some biochemical parameters were measured,such as the amount of antibody of gastric pylorus twist bacilli in serum. The SOD activity and MDA, NO amount of serum and gastric mucosal in rats of acetic induced gastric ulcer models were measured.RESULT:Ethyl acetate extraction of lonicera Caerulea L var edulis turcz Ex herd (EELC) could markedly stimulate the healing of acetic acid induced gastric ulcer.The two dose groups (2g/kg, 4g/kg)were all significal different from that of control group
(p<0.05 ^ p<0.01) and the gastric ulcer rates of inhibition were 53.6% and 84.2respectively,but had no significantly differently from the Cimetidine group(2g/kg).EELC could markedly reduce the gastric ulcer of grain alcohol induced (p<0.05^ p<0.0k p<0.01).The gastric ulcer rates of inhibition of the three dose group(lg/kg, 2g/kg^ 4g/kg)were49.05%,58.49% and 67.92%.Its were all significantly different from that of control group (p<0.05^p<0.0kp<0.01), but had no significantly differently from the cimetidine group (2g/kg).EELC (lg/kg^2g/kg^4g/kg) could inhibit the formation of indomethacin induced gastric ulcer (p<0.05^ p<0.01 ^ p<0.01).The gastric ulcer rates of inhibition of three dose groups were 24.4%^ 35.6% and 64.4%(p<0.05 N p<0.01 ^ p<0.01) ,and its were significantly differently from the control group,but had no significantly from the cimetidine group (0.2g/kg).EELC (lg/kg ? 2g/kg) could inhibit reserpine induced the gastric ulcer ,and were significantly from that of control group(p<0.01 ^ p<0.01).the gastric ulcer rates of inhibition of the two dose groups were 40.7% and 61.1% ., 79.6%, but had no significantly differently from the cimetidine group (2g/kg).EE1C could significal reduce the amount of antibody of gastric pylorus twist bacilli (p<0.05^ p<0.01).Its were all significantly different from that of the control group.(p<0.05^ p<0.01).Its had differently from cimetidine control (2g/kg).EELC (4g/kg) markedly increased the activity of SOD in gastric ulcer juicejt was significantly differently from that of the control group (p<0.05),but it little dose (2g/kg) had no effect on SOD activity in gastric mucosal juice .EELC had no effect on SOD activity in serum.EELC had no effect on the MDA amount of serum and mucosal juice .EELC had no effect on the NO content of serum and gastric mucosal juice. CONCLUSIONrEELC is the effectual portion of LC in the using of preventive and curative action on experiment gastric ulcer in rats.The results indicate that the EELC had preventive and curative effect against chronic and some acute gastric ulcer .Its mechanisms of the anti-ulcer action maybe associated with its ability to enhance the gastric mucosal defending,weaken the attacking factors and accelerate the
regeneration and repair of injured mucosal by means of improving the mucosal blood circulation resisting the free radicals > inhibiting the lipid peroxidation ^ stimulating the synthesis of DNA> RNA and protein > inhibiting the reproducer of bacillus.
引文
[1] 李淑琴,李延冰,姜福臣,都昌杰..野生植物-蓝靛果营养成分研究.东北农业大学学报,1994,25 (4):401-404
[2] 郎杰,隋政,高慧英.蓝靛果的降压研究.中医药信息,1996,30 (1):45-46
[3] 黄普英.我国东北地区蓝靛果初步研究.自然资源研究,1982,50 (1):57-62
[4] 张欣.野生蓝靛果忍冬资源开发.北方园艺,1997,61 (5):28-29
[5] 许双庆.蓝靛果的人工栽培.黑龙江林业,1986 (10):8-9
[6] 洪醇赞,金胜日.蓝靛果中总黄酮类含量测定方法的探讨.延边大学医学学报,2000,23 (10):41-45
[7] 葛正华,李延冰.蓝靛果果实中黄酮类成分的检识分析.中医药学报,1995 12 (4):56-57
[8] 候江雁,李延冰.蓝靛果果实中黄酮类的含量测定.黑龙江医学,2001,15 (3):42-43
[9] 候江雁,李延冰,翟立杰.蓝靛果保健颗粒的制备和毒理实验.中医药学报,2001,2 (3):58-59
[10] 金成旭,韩春姬,李莲姬.蓝靛果汁拮抗环磷酰胺诱发骨髓细胞微核.延边大学医学学报.2001,24(2):87-89
[11] 王启伟,金政,李相伍,金美善.蓝靛果汁对四氯化碳损伤的小鼠血清谷草转氨酶的影响.延边大学医学学报,2001,24 (1):18-20
[12] 金政,王启伟,金美善,李莲姬.蓝靛果抗疲劳实验研究.延边大学医学学报,2001,24(1):16-17
[13] 颜承云,谷继伟.蓝靛果忍冬果实黄酮类成分总含量的动态分析.中国野生植物资源,2004,23(2):51-52
[14] 陈国静,姚恩峰,姚月梅,邹立华.蓝靛果汁对小鼠免疫功能影响的实验研究..中国中医药科技,2004,11(1):27-27
[15] 姜振平,杨爱.浅谈蓝靛果忍冬栽培技术.黑龙江林业,2001,45(10):27-27
[16] 颜承云,谷继伟.蓝靛果忍冬性状与显微鉴别的研究.黑龙江医药科学,2003,26(3):15-17
[17] 周冬跃,李淑,邹威.野生蓝靛果的开发和人工繁殖.特种经济动植物,2003,6(5): 30-30
[18] 颜承云,杨治伟.黑龙江省蓝靛果忍冬的资源调查.中国野生植物资源,2002,21(2):18-19
[19] 金政,洪淳赞,李相伍,王启伟.蓝靛果对四氯化碳操作小鼠肝脏保护的组织化学研究.延边大学医学学报,2001,24(1):18-20
[20] 韩京振,金政,李松竹,李相伍.蓝靛果抗氧化作用的实验研究.中国中医药科技,2002,9(1):45-46
[21] 张守仁.呋喃唑酮和一些常用药对四种胃溃疡模型的影响.药学学报,1984,19 (1) 5—12
[22] 姚月梅,张英艳,邹立化.发酵蓝靛果汁抑菌作用实验研究.中国微生态学杂志,2002,14(4):216-220
[23] 张静,佘菲菲,陈月秀,陈豪.幽门螺杆菌cagA、oipA、iceA1基因的检测及其意义.中国卫生检验杂志,2004,14(2):133-134
[24] XiaoChang, XueYong, JieWu,MingTangGao, WenGuangL. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats. World Journal of Gastroenterology(世界胃肠病学杂志:英文版), 2004, 10(7):1032-1036
[25] 孙凤蓬,宋于刚.Cahgnes of G cells and D cells in the antral mucosa in rat experimental gastric ulcer. Journal of Medical Colleges of PLA(中国人民解放军军医大学学报:英文版), 2002, 17(1):39-41
[26] 来启槐,吴建波,谭映霞.胃粘膜组织中一氧化氮合酶-mRNA与老年胃溃疡的相关性研究.中华消化内镜杂志,2004,21(1):47-47
[27] 王巧民.幽门螺杆菌感染的诊断与治疗.中国临床保健杂志,2004,7(2):147-150
[28] 陆慧荣,卢金福,杨舜民,许立.香芍胃药胶囊抗大鼠溃疡作用.中药新药与临床药理,2004,15(2):104-106
[29] 冉志华.消化性溃疡的历史变迁.胃肠病学,2004,9(1):3-4
[30] 林长征,曹永孝,李长顺,刘静.平溃散对急性胃溃疡及胃粘膜损伤的保护作用.中成药,2004,26(2):128-130
[31] 陈英良,章晓萍.幽门螺杆菌感染与胃十二指肠疾病的关系..中国交通医学杂 志,2004,18(1):46-47
[32] 张薇,潘华峰,王茵萍,邹移海.慢性胃溃疡发生机理的实验研究.四川医学,2004,25(2):158-159
[33] 蒋毅萍,吴航宇,陈超,余云华.胃可宁对实验性胃溃疡面的保护作用研究..时珍国医国药,2004,15(1):2-3
[34] 神谷茂,吴祥林,陈平纡.幽门螺杆菌感染的动物模型..生物制品快讯,2004(1):19-20
[35] 廖健中,李嘉龙,赖永智,黄世鸿.Accuracy of three diagnostic tests used alone and in combination for detecting Helicobacter pylori infection in patients with bleeding gastric ulcers. Chinese Medical Journal(中华医学杂志:英文版),2003,116(12):1821-1826
[36] Jin-YanLuo, Chun-YanNiu. Effect of a single oral dose of rabeprazole on nocturnal acid breakthrough and nocturnal alkaline amplitude.World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(11):2583-2586
[37] Feng-ChanHan, MinGong, Han-ChongNg, BowHo. Identification of H. pyloristrain specific DNA sequences between two clinical isolates from NUD and gastric ulcer by SSH.. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(8):1747-1751
[38] Jin-ShengGuo. Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(8):1767-1771
[39] HarryHua-XinagXia, ShiuKumLam. Antralization at the edge of proximal gastric ulcers, Does Helicobacterpyloriinfection play a role. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(6):1265-1269.
[2] 郎杰,隋政,高慧英.蓝靛果的降压研究.中医药信息,1996,30 (1):45-46
[3] 黄普英.我国东北地区蓝靛果初步研究.自然资源研究,1982,50 (1):57-62
[4] 张欣.野生蓝靛果忍冬资源开发.北方园艺,1997,61 (5):28-29
[5] 许双庆.蓝靛果的人工栽培.黑龙江林业,1986 (10):8-9
[6] 洪醇赞,金胜日.蓝靛果中总黄酮类含量测定方法的探讨.延边大学医学学报,2000,23 (10):41-45
[7] 葛正华,李延冰.蓝靛果果实中黄酮类成分的检识分析.中医药学报,1995 12 (4):56-57
[8] 候江雁,李延冰.蓝靛果果实中黄酮类的含量测定.黑龙江医学,2001,15 (3):42-43
[9] 候江雁,李延冰,翟立杰.蓝靛果保健颗粒的制备和毒理实验.中医药学报,2001,2 (3):58-59
[10] 金成旭,韩春姬,李莲姬.蓝靛果汁拮抗环磷酰胺诱发骨髓细胞微核.延边大学医学学报.2001,24(2):87-89
[11] 王启伟,金政,李相伍,金美善.蓝靛果汁对四氯化碳损伤的小鼠血清谷草转氨酶的影响.延边大学医学学报,2001,24 (1):18-20
[12] 金政,王启伟,金美善,李莲姬.蓝靛果抗疲劳实验研究.延边大学医学学报,2001,24(1):16-17
[13] 颜承云,谷继伟.蓝靛果忍冬果实黄酮类成分总含量的动态分析.中国野生植物资源,2004,23(2):51-52
[14] 陈国静,姚恩峰,姚月梅,邹立华.蓝靛果汁对小鼠免疫功能影响的实验研究..中国中医药科技,2004,11(1):27-27
[15] 姜振平,杨爱.浅谈蓝靛果忍冬栽培技术.黑龙江林业,2001,45(10):27-27
[16] 颜承云,谷继伟.蓝靛果忍冬性状与显微鉴别的研究.黑龙江医药科学,2003,26(3):15-17
[17] 周冬跃,李淑,邹威.野生蓝靛果的开发和人工繁殖.特种经济动植物,2003,6(5): 30-30
[18] 颜承云,杨治伟.黑龙江省蓝靛果忍冬的资源调查.中国野生植物资源,2002,21(2):18-19
[19] 金政,洪淳赞,李相伍,王启伟.蓝靛果对四氯化碳操作小鼠肝脏保护的组织化学研究.延边大学医学学报,2001,24(1):18-20
[20] 韩京振,金政,李松竹,李相伍.蓝靛果抗氧化作用的实验研究.中国中医药科技,2002,9(1):45-46
[21] 张守仁.呋喃唑酮和一些常用药对四种胃溃疡模型的影响.药学学报,1984,19 (1) 5—12
[22] 姚月梅,张英艳,邹立化.发酵蓝靛果汁抑菌作用实验研究.中国微生态学杂志,2002,14(4):216-220
[23] 张静,佘菲菲,陈月秀,陈豪.幽门螺杆菌cagA、oipA、iceA1基因的检测及其意义.中国卫生检验杂志,2004,14(2):133-134
[24] XiaoChang, XueYong, JieWu,MingTangGao, WenGuangL. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats. World Journal of Gastroenterology(世界胃肠病学杂志:英文版), 2004, 10(7):1032-1036
[25] 孙凤蓬,宋于刚.Cahgnes of G cells and D cells in the antral mucosa in rat experimental gastric ulcer. Journal of Medical Colleges of PLA(中国人民解放军军医大学学报:英文版), 2002, 17(1):39-41
[26] 来启槐,吴建波,谭映霞.胃粘膜组织中一氧化氮合酶-mRNA与老年胃溃疡的相关性研究.中华消化内镜杂志,2004,21(1):47-47
[27] 王巧民.幽门螺杆菌感染的诊断与治疗.中国临床保健杂志,2004,7(2):147-150
[28] 陆慧荣,卢金福,杨舜民,许立.香芍胃药胶囊抗大鼠溃疡作用.中药新药与临床药理,2004,15(2):104-106
[29] 冉志华.消化性溃疡的历史变迁.胃肠病学,2004,9(1):3-4
[30] 林长征,曹永孝,李长顺,刘静.平溃散对急性胃溃疡及胃粘膜损伤的保护作用.中成药,2004,26(2):128-130
[31] 陈英良,章晓萍.幽门螺杆菌感染与胃十二指肠疾病的关系..中国交通医学杂 志,2004,18(1):46-47
[32] 张薇,潘华峰,王茵萍,邹移海.慢性胃溃疡发生机理的实验研究.四川医学,2004,25(2):158-159
[33] 蒋毅萍,吴航宇,陈超,余云华.胃可宁对实验性胃溃疡面的保护作用研究..时珍国医国药,2004,15(1):2-3
[34] 神谷茂,吴祥林,陈平纡.幽门螺杆菌感染的动物模型..生物制品快讯,2004(1):19-20
[35] 廖健中,李嘉龙,赖永智,黄世鸿.Accuracy of three diagnostic tests used alone and in combination for detecting Helicobacter pylori infection in patients with bleeding gastric ulcers. Chinese Medical Journal(中华医学杂志:英文版),2003,116(12):1821-1826
[36] Jin-YanLuo, Chun-YanNiu. Effect of a single oral dose of rabeprazole on nocturnal acid breakthrough and nocturnal alkaline amplitude.World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(11):2583-2586
[37] Feng-ChanHan, MinGong, Han-ChongNg, BowHo. Identification of H. pyloristrain specific DNA sequences between two clinical isolates from NUD and gastric ulcer by SSH.. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(8):1747-1751
[38] Jin-ShengGuo. Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(8):1767-1771
[39] HarryHua-XinagXia, ShiuKumLam. Antralization at the edge of proximal gastric ulcers, Does Helicobacterpyloriinfection play a role. World Journal of Gastroenterology(世界胃肠病学杂志:英文版),2003,9(6):1265-1269.