【作者】 王雪；

【导师】 任雷鸣；

【作者基本信息】 河北医科大学 ， 药理学， 2008， 硕士

【摘要】 目的:观察卡巴胆碱、组胺和5-羟色胺对兔离体胃体上部不同区域纵行肌功能性活动的影响并探讨其受体机制;分析核苷和核苷酸类物质对兔胃体上部纵行肌的作用和作用特点。方法:制备兔胃体上部前壁胃大弯处上、中、下三段纵行肌标本,胃体上部胃大弯旁开一厘米处上、中、下三段纵行肌标本及胃体上部前壁胃小弯处纵行肌标本。观察兔胃体上部不同部位肌条对卡巴胆碱、组胺、5-羟色胺、KCl的反应,分析ATP、ADP、UTP和腺苷对兔胃体上部纵行肌的作用及作用机制。结果:1胃大弯不同部位纵行肌对同一药物的反应卡巴胆碱(0.01~30μmol?L-1)、组胺(0.1~300μmol?L-1)、5-羟色胺(0.01~30μmol?L-1)及KCl(2~75mmol?L-1)使胃体上部胃大弯上、中、下三段纵行平滑肌产生浓度依赖性收缩反应。在上段纵行肌标本,上述药物所产生的收缩反应显著强于中段和下段(P<0.05);下段纵行肌标本仅在高浓度药物作用下才产生较弱的收缩反应。2胃大弯同一部位纵行肌对不同药物的反应在胃大弯上段纵行肌标本,卡巴胆碱产生的最大收缩反应(Emax)显著大于KCl(P<0.05),远大于组胺和5-羟色胺。在胃大弯中段纵行肌标本,卡巴胆碱、组胺和5-羟色胺所致收缩反应的Emax约为KCl Emax的50%、18%和8%。在胃大弯下段纵行肌标本,卡巴胆碱和组胺所致收缩反应的Emax约为KCl Emax的30%和11%,5-羟色胺的Emax与组胺相同。3胃小弯纵行肌对不同药物的反应三种受体激动药及KCl使胃小弯纵行肌产生浓度依赖性收缩反应,各药物产生Emax的序列为卡巴胆碱>KCl>5-羟色胺>组胺。4药物诱发胃大弯及胃小弯纵行肌收缩反应的EC50值卡巴胆碱使胃小弯纵行肌标本产生收缩反应的EC50值为0.36±0.17μmol?L-1,显著小于卡巴胆碱使大弯上纵肌标本产生收缩反应的EC50值(1.32±0.62μmol?L-1)。组胺使胃大弯上、中、下三段纵行肌标本以及胃小弯处纵行肌标本产生收缩反应的EC50值,在各标本间无显著性差异(P>0.05),5-羟色胺的实验结果与组胺相同。实验结束后,称量兔胃体上部不同部位各肌条标本的湿重,未见显著性差异(P>0.05)。5胃大弯旁开一厘米处不同部位纵行肌对同一药物的反应三种受体激动药及KCl使胃体上部前壁胃大弯旁开一厘米处上、中、下三段纵行肌产生浓度依赖性收缩反应。在三种标本上,卡巴胆碱产生的Emax及EC50值无显著性差异(P>0.05);组胺及5-羟色胺的作用特点与卡巴胆碱相同。6 ATP、ADP、UTP和腺苷对胃体上部纵行肌的作用ATP(0.1~300μmol?L-1)、ADP(0.01~30μmol?L-1)、UTP(0.01~30μmol?L-1)和腺苷(0.1~100μmol?L-1)分别使兔胃体上部纵行肌标本产生浓度依赖性收缩反应。ADP的Emax为0.3μmol?L-1卡巴胆碱诱发收缩反应的16.2±2.6(%),其Emax值明显低于ATP(P<0.05);腺苷的Emax值与ATP相近(P>0.05),二者的Emax值均明显小于UTP(P<0.05)。7 ATP对胃体上部纵行肌的舒张作用卡巴胆碱(0.1μmol?L-1)引起的收缩反应为3.99±0.82g,在卡巴胆碱预收缩条件下,ATP产生明显的浓度依赖性舒张反应。结论:研究结果表明,兔胃体上部组织中,胃大弯处上段纵行肌标本所含的平滑肌数量显著高于下段纵行肌标本。兔胃体上部组织的胃大弯上、中、下纵行肌标本中,所含有的功能性M胆碱受体、组胺受体和5-羟色胺受体的种类相同;但是,这些受体的分布密度在各标本中不同。ATP对兔离体胃体上部纵行肌标本具有收缩和舒张双重作用,其诱发收缩反应的特征与UTP、ADP和腺苷不同。核苷及核苷酸类物质所介导的兔胃体上部纵行肌收缩和舒张作用可能与P受体的多种亚型有关。更多还原

【Abstract】 Objective: To investigate the effects of carbachol, histamine and 5-HT on the longitudinal muscle strips isolated from different regions of the rabbit upper gastric body, and the effects of nucleoside and nucleotides in the longitudinal muscle strips of the rabbit upper gastric body.Methods: Three longitudinal muscle strips (upper, middle and lower strips) of the upper gastric body obtained along the greater curvature in anterior surface side, and three longitudinal muscle strips (upper, middle and lower strips) obtained from the region 1 cm to the greater curvature were used in this study. A longitudinal muscle strip near the lesser curvature in anterior surface side was used as control. Responses to carbachol, histamine, 5-HT and KCl were observed in the three longitudinal muscle strips obtained along the greater curvature. The effects of ATP, ADP, UTP and adenosine on longitudinal muscle strips of the rabbit upper gastric body were investigated.Results:1 Responses of longitudinal muscle strips obtained along the greater curvature to the same agent Carbachol (0.01~30μmol?L-1), histamine (0.1~300μmol?L-1), 5-HT (0.01~30μmol?L-1) and KCl (2~75mmol?L-1) produced concentration-dependent contractile responses in the longitudinal muscle strips (upper, middle and lower strips), and the contractile responses to the four agents in upper strip were much stronger than those in middle and lower strips (P<0.05); a small contraction was produced by the four agents only at a higher concentration in lower strip.2 Responses to different agents in one longitudinal muscle strip obtained along the greater curvatureIn the upper strip, the maximal contractile response (Emax) calculated from the cumulative concentration-response curve (CCRC) for carbachol was significantly bigger than that for KCl (P<0.05), and much bigger than that for histamine or 5-HT. In the middle strip, the values of Emax calculated from CCRCs for carbachol, histamine and 5-HT were about 50%, 18% and 8% (normalized to KCl Emax). In the lower strip, the values of Emax calculated from CCRCs for carbachol and histamine were about 30% and 11% (normalized to KCl Emax). The experimental result of 5-HT was the same as that of histamine.3 Responses to different agents in the longitudinal muscle strip near the lesser curvatureCarbachol, histamine, 5-HT and KCl produced concentration-dependent contractile responses in longitudinal muscle strips near the lesser curvature, and the order of Emax amplitude was carbachol>KCl>5-HT>histamine. 4 EC50 values of the agents producing contractile responses in longitudinal muscle strips obtained from the greater curvature and lesser curvatureThe EC50 value of carbachol (0.36±0.17μmol?L-1) in longitudinal muscle strip of the lesser curvature was less than that (1.32±0.62μmol?L-1) in the upper strip of the greater curvature, but the EC50 values of histamine were the same among the 4 longitudinal muscle strips of the greater curvature (upper, middle and lower strips) and the lesser curvature (P>0.05). The experimental result of 5-HT was the same as that of histamine. At the end of each experiment, the wet weight of strip was weighed, and there was no significant difference among the several experiment groups (P>0.05).5 Responses of longitudinal muscle strips obtained from the region 1cm to the greater curvature to the same agentCarbachol, histamine, 5-HT and KCl produced contractile responses in a concentration-dependent manner in the three longitudinal muscle strips (upper, middle and lower strips). The values of Emax and EC50 calculated from CCRC for carbachol were not different among upper, middle and lower strips (P>0.05). The experimental results of histamine and 5-HT were the same as those of carbachol.6 Effects of ATP, ADP, UTP and adenosine on longitudinal muscle strips of the upper gastric bodyATP (0.1~300μmol?L-1), ADP (0.01~30μmol?L-1), UTP (0.01~30μmol?L-1) and adenosine (0.1~100μmol?L-1) produced concentration-dependent contractile responses in longitudinal muscle strips of the rabbit upper gastric body. Emax value (16.2±2.6 %, normalized to 0.3μmol?L-1 carbachol) of ADP was much weaker than that of ATP (P<0.05). There was no significant difference between Emax values of ATP and adenosine (P>0.05), and the Emax amplitude of ATP and adenosine was much weaker than that of UTP (P<0.05).7 Relaxant responses to ATP in longitudinal muscle strips of the upper gastric bodyThe contractile response to 0.1μmol?L-1 carbachol was 3.99±0.82g. In the preparations precontracted with carbachol (0.1μmol?L-1), ATP produced obviously relaxant responses in a concentration-dependent manner.Conclusion:In the rabbit upper gastric body, the upper longitudinal muscle strip of the greater curvature contains much more smooth muscle than the lower longitudinal muscle strip. In longitudinal muscle strips (upper, middle and lower strips) obtained from the greater curvature, the subtypes of functional muscarinic receptor, histamine receptor and 5-HT receptor are the same, however, the distribution density of those functional receptors is significantly different among the upper, middle and lower strips.ATP produces contractile and relaxant responses in longitudinal muscle strips of the rabbit isolated upper gastric body. ATP-induced contraction is different from that of UTP, ADP or adenosine in pharmacological profile. The contractile and relaxant responses to nucleoside and nucleotides might be mediated by several subtypes of P receptors.更多还原