Ghrelin对糖尿病大鼠海马神经元凋亡及其认知功能的影响

摘要

Objective To explore the effects of Ghrelin on the hippocampus neuronal apoptosis and the cognitive function of diabetic rats. Methods Forty SD male rats were meanly divided into normal group, diabetic modle group, Ghrelin treatment group, Ghrelin and D-lys-3-GHRP-6 treatment gooup randomly. Streptozotocin-diabetic rats model were established, diabetic rats with depression were screened by open-field test, learning and memory behaviors were measured using a spatial version of the Morris water maze test. The mRNA level of caspase-3 was examined by RT-PCR. The protein expression of capase-3, BCL-xl were examined with immunohistochemical method. Meanwhile the hippocampus neuronal apoptosis were measured by TUNEL. Results Comparing to the normal group, learning and memory level of diabetic group and Ghrelin + D - lys - 3 - GHRP - 6 trreatment group decreased transparently(P ＜0. 05), the mRNA and protein level of caspase-3 in hippocampal neuron increased and the protein expression of BCL-xl were descendent ( P ＜ 0. 05 ), the number of neuronal apoptosis increased markedly ( P ＜ 0. 05 ). Learning and memory level in the Ghrelin treatment group were much better than diabetic modle group (P ＜ 0. 05 ), the changes of caspase-3 in hippocampus significantly reduced ( P ＜ 0. 05 ) and the expression of BCL-xl in hippocampus inceased in the Ghrelin treatment group and the number of apoptotic neurons of the hippocampus was decreased remarkably (P ＜ 0. 05 ). Conclusion Ghrelin may improve cognitive ability in diabetic rats,which increased the expression of BCL-xl and decreased the expression of caspase-3 to inhibit hippocampus neuronal apoptosis.%目的 观察Ghrelin对糖尿病大鼠海马神经元凋亡及其认知功能的影响.方法 40只雄性SD大鼠随机均分为对照组、糖尿病组、糖尿病+Ghrelin组和糖尿病+Ghrelin+D-lys3-GHRP-6组,每组10只.建立STZ糖尿病模型,open-field实验排除合并抑郁症的糖尿病大鼠,Morris水迷宫测试学习与记忆能力,RT-PCR检测海马caspase-3mRNA的表达,免疫组化检测海马神经元caspase-3和BCL-xl蛋白表达,原位末端标记法检测海马神经元的凋亡.结果 与对照组大鼠相比,糖尿病组和糖尿病+Ghrelin+D-lys3-GHRP-6组学习与记忆能力显著受损(P<0.05),海马部位的caspase-3 mRNA及蛋白表达明显升高(P<0.05),BCL-xl蛋白表达显著下降(P<0.05),海马神经元的凋亡增加了49%(P<0.05).糖尿病+Ghrelin组学习和记忆成绩明显优于糖尿病组(P<0.05),其海马部位的caspase-3 mRNA及蛋白表达显著下降(P<0.05),BCL-xl蛋白表达明显升高(P<0.05),海马神经元的凋亡减少了42%.结论 Ghrelin对糖尿病大鼠认知功能有改善作用,机制可能与下调caspase-3、上调BCL-xl的表达从而抑制神经元的凋亡有关.