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柴术宁肠方对肠易激综合征模型大鼠5-羟色胺信号系统的影响

Effect of Chaizhu Ningchang Fang on 5-Hydroxytryptamine Signaling System of Irritable Bowel Syndrome Model Rats

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【作者】 邱悦李怡胡浪李潇然朱嘉煜文瑞杨星昊

【Author】 QIU Yue;LI Yi;HU Lang;LI Xiao-ran;ZHU Jia-yi;WEN Rui;YANG Xing-hao;New Drug Research Center,School of Life Science,Nanjing Normal University;

【机构】 南京师范大学生命科学学院新药研究中心

【摘要】 目的:探讨柴术宁肠方对肠易激综合征(IBS)模型大鼠5-羟色胺(5-HT)信号系统的影响。方法:60只SD雄性大鼠随机分为正常组、模型组、匹维溴铵组(15 mg·kg-1)、柴术宁肠方低、中、高剂量组(2.5,5,10 g·kg-1)。采用复合应激法建立肠易激综合征(IBS)大鼠模型,造模成功后连续灌胃给药1周,每日1次,正常组及模型组给予等体积生理盐水,考察一般状态半定量积分、腹部撤回反射(AWR)评分及最小容量阈值;用酶联免疫法(ELISA)检测大鼠血清5-HT水平,结肠色胺酸羟化酶1(TPH1),5-羟色胺转运体(SERT),5-羟色胺3受体(5-HT3R),5-羟色胺4受体(5-HT4R)水平;RT-PCR法检测结肠TPH1,SERT,5-HT3R,5-HT4R mRNA的表达。结果:与正常组比较,模型组一般状态半定量积分、腹部撤回反射评分及最小容量阈值均有显著性差异(P<0.01);模型组血清5-HT和结肠的TPH1,5-HT3R水平及基因表达明显增高和上调(P<0.01,P<0.05);结肠SERT,5-HT4R水平及基因表达显著降低和下调(P<0.05)。与模型组比较,柴术宁肠方血清5-HT和结肠TPH1水平明显下调(P<0.05,P<0.01);结肠5-HT3R水平及基因表达显著下调(P<0.05);结肠SERT,5-HT4R水平及基因表达显著上调(P<0.05)。结论:柴术宁肠方可能通过对IBS模型大鼠5-HT信号通路的多靶点调节,降低IBS大鼠内脏敏感性,缓解IBS症状。

【Abstract】 Objective: To investigate the effect of Chaizhu Ningchang Fang( CZNCF) on 5-hydroxytryptamine( 5-HT) signal system of irritable bowel syndrome( IBS) model rats. Method: Totally 60 male SD rats were randomly divided into the normal group,the model group,the dicetel group and CZNCF high,medium and low doses( 2. 5,5,10 g·kg- 1) groups. The IBS rat model was established by means of composite stress. After the successful modeling,the rats were orally administered with drugs once a day for one week,and the normal group and the model group were given isovolumetric normal saline,in order to detect the semi-quantitative score in general state,abdominal withdrawal reflex( AWR) score and minimum volume threshold. The 5-HT level in rat serum,tryptophan hydroxylase1( TPH1),5-hydroxytryptamine transporter( SERT),5-hydroxytryptamine 3receptors( 5-HT3R) and 5-hydroxytryptamine 4 receptors( 5-HT4R) levels in colon were determined by ELISA.The mRNA expressions of TPH1,SERT,5-HT3 R and 5-HT4 R were detected by RT-PCR method. Result:Compared with the normal group,the model group showed significant differences in all of semi-quantitative score in general state,AWR score and minimum volume threshold increase( P < 0. 01) and up-regulation in 5-HT in serum and TPH1,5-HT3 R in colon( P < 0. 05,P < 0. 01) and decrease in the levels and gene expressions of SERT and5-HT4 R in colon( P < 0. 05). Compared with the model group,CZNCF significantly decreased the concentrations of the 5-HT in serum,the level of TPH1 in colon,5-HT3 R level and gene expression in colon,and up-regulated SERT,5-HT4 R level and gene expression in colon( P < 0. 05). Conclusion: CZNCF may reduce the visceral sensitivity of IBS rats and relieve IBS symptoms by regulating multiple targets of the 5-HT signal pathway of IBS model rats.

【基金】 江苏省新药创制基金项目(20031226);江苏省高校科研成果产业化推进项目(JH10-21)
  • 【文献出处】 中国实验方剂学杂志 ,Chinese Journal of Experimental Traditional Medical Formulae , 编辑部邮箱 ,2015年17期
  • 【分类号】R285.5
  • 【被引频次】17
  • 【下载频次】311
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