替加色罗对糖尿病大鼠胃排空功能及Ghrelin、P物质表达的影响

Effect of tegaserod on gastric emptying and the expression of ghrelin and substance P in diabetic rats

目的:研究替加色罗对糖尿病大鼠胃排空功能及胃组织Ghrelin、P物质表达的影响,探讨替加色罗对糖尿病胃轻瘫的治疗作用及其可能的机制.方法:50只清洁级♂Wistar大鼠随机分为正常对照组(NC组,n=10)、糖尿病组(DM组,n=10)、低剂量替加色罗治疗组(TEG-L组,n=10)、中剂量替加色罗治疗组(TEG-M组,n=10)和高剂量替加色罗治疗组(TEG-H组,n=10).ip链脲佐菌素(STZ)制备糖尿病大鼠模型,8 wk后分别以0.1,0.5和1 mg/kg的剂量给予TEG-L,M和H组大鼠ip替加色罗连续3 d,采用酚红灌胃法检测胃排空,免疫组化技术检测各组大鼠胃黏膜Ghrelin与胃窦组织SP的表达.结果:TEG各组大鼠Ghrelin(34.721±6.759,33.547±6.255,35.141±5.987)与SP的积分光密度(13.548±1.078,13.952±1.246,11.845±1.567)均低于NC组(Ghrelin:43.514±5.323,P<0.05,P<0.01,P<0.01;SP:16.383±2.275,均P<0.01)而高于DM组(Ghrelin:26.626±4.596,均P<0.05;SP:9.257±1.636,均P<0.01);Ghrelin积分光密度在TEG各组之间无显著性差异,而TEG-L,M组SP积分光密度均高于TEG-H组(均P<0.05).结论:替加色罗可通过促进胃组织Ghrelin与SP的表达释放来改善糖尿病大鼠延迟的胃排空.

Abstract AIM： To investigate the effect of tegaserod on gastric emptying and the expression of ghrelin and substance P （SP） in diabetic rats, and to explore the therapeutic effect of tegaserod on diabetic gastroparesis and its possible mechanism. METHODS： Fifty Wistar rats were randomly divided into five groups： a normal control group （NC group, n = 10）, a diabetes mellitus group （DM group, n = 10）, a low dose tegaserodtreated group （TEG-L group, n = 10）, a moderate dose tegaserod-treated group （TEG-M group, n = 10） and a high dose tegaserod-treated group （TEG-H group, n = 10）. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ）. After 8 weeks, tegaserod was administered by intraperitoneal injection at doses of 0.1 mg/kg, 0.5 mg/kg and 1mg/kg in TEG-L, TEG-M and TEG-H groups, respectively, for 3 days. Gastric emptying was measured by intragastric administration of phenol red. The expression of ghrelin in the gastric mucosa and SP in the gastric antrurn was detected by immunohistochemistry. RESULTS： The staining intensities for ghrelin and SP in all TEG groups were significantly decreased compared with those in the NC group （ghrelin： 34.721 ± 6.759, 33.547 ± 6.255, 35.141 ± 5.987 vs 43.514 ± 5.323, P 〈 0.05, P 〈 0.01, P 〈 0.01; SP： 13.548 ± 1.078, 13.952 ± 1.246, 11.845 ± 1.567 vs 16.383 ± 2.275, all P 〈 0.01） and increased compared with the DM group （ghrelin： 26.626 ± 4.596, all P 〈 0.05; SP： 9.257 ± 1.636, all P 〈 0.01）. However, the differences in ghrelin staining intensities among TEG groups were not statistically significant. The staining intensities for SP in the TEG-L and TEG-M groups were increased compared with the TEG-H group （both P 〈 0.05）. CONCLUSION： Tegaserod may improve delayed gastric emptying in diabetic rats by enhancing the expression and release of ghrelin and SP.