糖尿病大鼠不同阶段Ghrelin变化与胃排空关系的研究

Relationship between ghrelin and gastric emptying in diabetic rats at different stages

目的观察不同阶段糖尿病大鼠Ghrelin的变化情况与胃运动异常之间的联系,了解在糖尿病的不同阶段Ghrelin对胃排空的影响。方法 66只Wistar大鼠随机分为2周糖尿病组(DM-2w)及对照组(NC-2w)、8周糖尿病组(DM-8w)及对照组(NC-8w)、20周糖尿病组(DM-20w)和对照病组(NC-20w)。高脂料喂养诱导胰岛素抵抗后以小剂量链脲佐菌素(STZ,30 mg/kg)腹腔注射,制作2型糖尿病大鼠模型。造模成功后第2周、第8周、第20周进行核素法胃排空测定胃半排时间、50 min胃内核素残留率;酶联免疫法测定血浆Ghrelin水平,免疫组化方法观察胃组织Ghrelin免疫阳性细胞密度。结果 (1)DM-2w组半排时间为(22.99±2.53)min,与NC-2w组(48.76±22.06)min比较胃排空明显加快,差异有统计学意义(P<0.01)。DM-8w组半排时间为(35.24±11.00)min,与NC-8w组(43.59±13.79)min比较差异无统计学意义(P>0.05)。DM-20w组半排空时间为(84.02±27.54)min,与NC-20w组(47.79±13.22)min比较胃排空时间延长,差异有统计学意义(P<0.01)。各对照组之间比较差异无统计学意义(P>0.05)。(2)DM-2w组大鼠血浆Ghrelin水平显著升高,与NC-2w组比较差异有统计学意义(P<0.05)。DM-8w组大鼠血浆Ghrelin水平与NC-8W组比较差异无统计学意义(P>0.05)。DM-20w组大鼠血浆Ghrelin水平与NC-20w组及DM-2w组比较差异有统计学意义(P<0.05)。各对照组之间差异无统计学意义(P>0.05)。(3)血浆Ghrelin水平与胃半排空时间呈负的直线相关。结论 (1)糖尿病的不同阶段胃动力的变化有着不同的形式,在早期以胃动力加速为主;随着糖尿病病程的进展,胃排空逐渐减慢延迟。(2)在胃动力变化的过程中,血浆Ghrelin也呈现出与胃动力变化类似的变化趋势。(3)血浆Ghrelin水平与胃半排空时间呈负相关。

Objective To investigate the relationship between ghrelin and gastric emptying in diabetic rats at different stages. Methods Sixty-six Wistar rats were randomly divided into six groups： 2 week diabetic group（DM-2w group） and 2-week control group（NC-2w group）, 8-week diabetic group（DM-8w group） and 8-week control group（NC-8w group）, 20-weeks diabetic group（DM-20 w group） and 20-week control group（NC-20 w group）.Type 2 diabetes model was induced in rats by intraperitoneal injection of a low dose of streptozotocin plus long-term high fat and high caloric laboratory chow. The gastric emptying half time（GET1/2） and 50 min residual rate were measured by single photon emission computed tomography（SPECT）, the level of ghrelin in plasma was detected by Enzyme-linked immunosorbent test（ELISA） and ghrelin immunoreactive positive cells were observed in gastric tissue at2 weeks, 8 weeks or 20 weeks, respectively before the rats were sacrificed. Those data were compared between the control and model groups. Results（1） The GET1/2 in DM-2w group was significantly faster than that in NC-2w group [（22.99±2.53） min vs（48.76±22.06） min, P〈0.01]. There was no difference between DM-8w group and NC-8w group（P〉0.05）. The GET1/ 2 in DM-20 w group was significantly lower than that in NC-20 w group [（84.02±27.54） min vs（47.79±13.22） min, P〈0.01].（2） The increased size of plasma ghrelin level in DM-2w group was significantly higher than that in DM-2w group（P〈0.05）. There were no differences between DM-8w group and NC-8W group（P〉0.05）.There were significant differences between DM-20 w group and NC-20 w group and DM-2w group（P〈0.05）.（3）There was a negative correlation between plasma ghrelin level and gastric half-emptying time. Conclusion（1） The changes of gastric motility varied at different stages of diabetes. In early stage, it presented accelerates gastric motility.With the progression of diabetes, gastric emptying gradually slowed down.（2） With the changes of gastric motility,ghrelin in plasma showed a similar trending with gastric motility.（3） There was a negative correlation between plasma ghrelin level and gastric half-emptying time.