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目的:研究下丘脑室旁核(paraventricular nucleus,PVN)注射胰高血糖素样肽-1(GLP-1)对糖尿病早期大鼠胃排空的影响,并探讨其相关作用机制。方法:60只清洁级雄性Wistar大鼠随机分为正常对照组(NC组),糖尿病组(DM组),GLP-1干预组(GLP-1组),每组各20只,后两组腹腔注射链脲佐菌素(STZ)制备糖尿病模型,分别于注射STZ2周、6周后每组随机取半数进行实验,实验前于无菌条件下大鼠一侧下丘脑PVN区埋置套管,GLP-1组经套管注入GLP-1,NC组及DM组注入等体积生理盐水。酚红灌胃法检测胃排空率,酶联免疫吸附法(ELISA)测定血浆GLP-1浓度,半定量RT-PCR法测定胃窦、胃底GLP-1RmRNA表达。结果:注射STZ 2周后,DM组较NC组胃排空率显著升高(P<0.01)。GLP-1组胃排空率低于DM组(P<0.01),血浆GLP-1浓度高于DM组及NC组(P均<0.05),胃窦GLP-1RmRNA表达明显高于DM组、NC组(P均<0.01)。注射STZ 6周后,DM组胃排空率高于NC组(P<0.01)。GLP-1组较DM组胃排空率显著降低(P<0.01),血浆GLP-1浓度、胃窦GLP-1RmRNA表达显著高于DM组、NC组(P均<0.01)。结论:下丘脑PVN区注射GLP-1后,可减慢糖尿病大鼠初期加速的胃排空,原因可能与血浆GLP-1浓度及胃窦GLP-1RmRNA表达增加有关。
Objective: To investigate the effect of glucagon-like peptide-1 (GLP-1) injected into paraventricular nucleus (PVN) on gastric emptying in early stage of diabetic rats and its related mechanism. Methods: Sixty clean male Wistar rats were randomly divided into normal control group (NC group), diabetic group (DM group) and GLP-1 intervention group (GLP-1 group) Diabetes model was induced by injection of streptozotocin (STZ). Two weeks after STZ2 injection, rats in each group were randomized to take half of them. Before the experiment, a cannula was embedded in the PVN area of rat hypothalamus under aseptic conditions. The GLP-1 group was injected with GLP-1 through the cannula. The NC group and the DM group were injected with equal volumes of normal saline. The gastric emptying rate was measured by gingival red staining, the concentration of plasma GLP-1 by enzyme-linked immunosorbent assay (ELISA), and the GLP-1R mRNA expression in gastric antrum and gastric fundus by semi-quantitative RT-PCR. Results: After 2 weeks of STZ injection, the gastric emptying rate in DM group was significantly higher than that in NC group (P <0.01). The GLP-1 group had a lower rate of gastric emptying than the DM group (P <0.01), the plasma concentration of GLP-1 was higher than that of the DM group and the NC group (P <0.05), and the GLP- Group (all P <0.01). After 6 weeks of STZ injection, the gastric emptying rate in DM group was higher than that in NC group (P <0.01). The gastric emptying rate in GLP-1 group was significantly lower than that in DM group (P <0.01). The plasma GLP-1 concentration and GLP-1 mRNA expression in gastric antrum were significantly higher than those in DM group and NC group (all P <0.01). CONCLUSION: GLP-1 in the PVN area of the hypothalamus can slow down the initial accelerated gastric emptying in diabetic rats, which may be related to the increase of plasma GLP-1 concentration and the expression of GLP-1R mRNA.