红霉素促动力作用的易感性与多巴胺受体D3和神经肽受体Y5(英文)  

Involvement of Dopamine D3 and Neuropeptide Y Y5 Receptors in Diabetic Gastroparetic Rats without Response to Erythromycin

作　　者：秦新裕[1] 王志刚[2] 刘凤林[1] 费俭[3] 崔大敷 陈绍亮[4] 

机构地区：[1]复旦大学附属中山医院普外科,上海200032 [2]上海交通大学附属第六人民医院普外科,上海200233 [3]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031 [4]复旦大学附属中山医院核医学科,上海200032

出　　处：《生物化学与生物物理学报》2003年第9期811-815,共5页

基　　金：国家自然科学基金资助项目 (No .3 0 0 70 73 8)~~

摘　　要：通过应用核素法测定糖尿病胃瘫大鼠的胃排空 ,建立了糖尿病胃瘫大鼠的模型 ;据此模型观察了小剂量红霉素 (3mg kg)对糖尿病胃瘫大鼠液相胃排空的影响。结果显示该药能够显著减小其胃排空的一小时残留率 (R1H) [(6 3%± 6 .8% )vs.(36 %± 3.8% ) ];但此作用具有显著个体差异 ,根据所设标准分成红霉素有效组 (E组 )和无效组 (F组 )后 ,发现两组疗效具有显著差异。应用受体相关基因芯片初步筛选了这两组大鼠胃窦组织的差异表达基因。结果筛选出 10条差异表达基因 ,其中对多巴胺受体D3和神经肽Y受体Y5基因进行了RT PCR半定量验证 ,结果与芯片一致 ,即D3和Y5基因在E组中的表达水平显著高于F组 [D3受体 :(0 .2 6± 0 .0 4 )vs.(0 .16± 0 .0 4 ) ;Y5受体 :(0 .94± 0 .10 )vs .(0 .6 8± 0 .0 9) ],而与正常对照组和阴性对照组间未见明显差异。结果表明 :小剂量红霉素可以改善糖尿病胃瘫大鼠的胃排空 ,其疗效有明显的个体差异 ;红霉素有效组多巴胺受体D3(DRD3)和神经肽受体Y5 (NPYY5 )表达水平显著高于红霉素无效组。提示这两种受体可能与红霉素促动力作用的易感性相关。Erythromycin may accelerate gastric emptying in animals and human probably as an motilin agonist, but its prokinetic effects show obvious individual disparity. This study was to find the mechanism of this phenomenon. Microarray analysis was used to screen genes that might be involved in the response of diabetic gastroparesis rats to erythromycin. It was found that erythromycin accelerated gastric emptying of diabetic rats with great individual disparity. Through microarray analysis we screened differential expression genes that might be involved in the effect of erythromycin. Among 10 genes screened out, dopamine D3 receptor (DRD3) and neuropeptide Y Y5 receptor (NPYY5) genes were submitted to RT-PCR quantification and showed consistent results with microarray. It can be concluded that erythromycin promote gastric emptying of gastroparetic rats; DRD3 and NPYY5 may be involved in prokinetic action of erythromycin; and targets other than motilin receptor of erythromycin might exist as prokinetics.

关 键 词：红霉素 促动力作用 易感性 多巴胺受体D3 神经肽受体Y5 糖尿病胃瘫 

分 类 号：R965[医药卫生—药理学]