红霉素对糖尿病结肠运动障碍和四种胃肠激素的影响

Effects of erythromycin on colon dysmotility and neuroendocrine peptides in diabetic mellitus

目的:应用红霉素对糖尿病大鼠离体结肠平滑肌自发性收缩进行干预,探讨其在糖尿病结肠动力障碍中与平滑肌运动、血浆和结肠组织中生长抑素,血管活性肠肽,胃动素,P物质等的相关性. 方法:建立糖尿病大鼠模型,制备糖尿病组、糖尿病红霉素治疗组和对照组大鼠离体近端结肠环行肌及纵行肌肌条, 应用张力换能器测定其静息张力、平均振幅、收缩频率等运动指标;用放免法同批测定三组大鼠血浆和结肠组织中生长抑素,血管活性肠肽,胃动素及P物质含量. 结果:糖尿病组结肠肌条自发性收缩多项指标均较对照组明显降低(P<0.01);红霉素治疗组结肠肌条收缩振幅和频率较糖尿病组明显增高(P<0.01).与对照组相比,糖尿病组血浆生长抑素、血管活性肠肽、胃动素增加(P<0.05),P物质降低(P<0.05),而结肠组织中生长抑素和血管活性肠肽降低(P<0.01,P<0.05),P物质增加(P<0.05),胃动素无显著差异;与糖尿病组相比,红霉素治疗组除血浆生长抑素升高(P<0.05)外,余三种激素(血浆和结肠组织中)均无显著差异.红霉素治疗组较糖尿病组血糖明显下降(P<0.01). 结论:红霉素通过对结肠平滑肌直接作用而改善糖尿病结肠运动障碍;他对胃肠激素影响不大;糖尿病结肠运动障碍与血浆和结肠组织中胃肠激素变化有关.

AIM: To investigate the effects of erythromycin on contractive activity of isolated proximal colon smooth muscle and the change of somatostatin, vasoactive intestinal peptide, motilin and substance P in diabetic mellitus rats. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: the control (n =10), the diabetic (n =10) and erythromycin (n =10). The resting tension, the mean contractile amplitude and frequency of spontaneous changes of isolated longitudinal, circular proximal colon smooth muscle strips were measured by transducer, and somatostatin, vasoactive intestinal peptide, motilin, substance P levels in plasma and proximal colon tissue extracts were measured by radioimmunoassay. RESULTS: In isolated proximal colon smooth muscle strips, the motility parameters were significantly lower in diabetic rats than those in control (P <0.01). After taking erythromycin, the colon motility parameters were significantly strengthened compared with those in diabetic rats (P<0.01). In diabetic rats, the plasma levels of somatostatin, vasoactive intestinal peptide and motilin were higher than those in control (P <0.05), while substance P level was decreased (P<0.05). In the proximal colon, the levels of somatostatin and vasoactive intestinal peptide were significantly lower than that in control (P<0.01, P<0.05), the level of substance P was higher than that in the control (P<0.05), and the level of motilin did not differ from that in the control (P>0.05). After taking erythromycin, the plasma level of somatostatin was higher than that in diabetic rats (P<0.05). The serum glucose was decreased in diabetic rats after erythromycin treatment (P<0.01). CONCLUSION: Erythromycin has direct effect on colon smooth muscle, and has little effect on neuroendocrine peptides. Colonic motility disorders in diabetes rats are related with the changes of neuroendocrine peptides' levels in plasma and colon tissue.