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目的探讨胃饥饿素(Ghrelin)及其受体(GHSR1a)的变化在血糖波动加速糖尿病脑病发病过程中的作用。方法 8只雄性Wistar大鼠为正常对照组(NC),16只雄性GK大鼠随机分为持续高血糖组(MS)与血糖波动组(MF)。MF组每日错时腹腔注射葡萄糖及皮下注射胰岛素造成血糖波动模型,MS组每日错时腹腔注射葡萄糖造成持续高血糖模型,NC组每日错时腹腔注射等剂量生理盐水,连续6周,每日观察大鼠一般体征。第6周对大鼠进行行为学检测,包括Morris水迷宫实验、Y迷宫实验;第6周末检测全日9个时间点血糖。麻醉大鼠,心脏采血,检测血清中TC与TG含量。断头取脑,分离海马,HE染色与甲苯胺蓝染色分别观察大鼠海马病理变化及神经元改变。RT-PCR与免疫组织化学分别检测海马中Ghrelin及GHSR1a mRNA与蛋白的表达。结果与NC组比较,MS组与MF组体重增长速度减慢,TC、TG含量升高(P<0.05或P<0.01),认知功能减退,海马病理及神经元改变严重,海马中Ghrelin及GHSR1amRNA与蛋白的表达减少(P<0.05或P<0.01);与MS组比较,MF组在TC、认知功能、海马病理改变、Ghrelin及GHSR1a蛋白的表达上的变化更加明显(P<0.05或P<0.01)。结论 Ghrelin与GHSR1a在糖尿病大鼠海马组织中的表达减少,其在血糖波动加速糖尿病脑病发病过程中发挥重要作用。
Objective To investigate the role of Ghrelin and its receptor (GHSR1a) in the pathogenesis of diabetic encephalopathy during the fluctuation of blood glucose. Methods Eight male Wistar rats were normal control group (NC). Sixteen male GK rats were randomly divided into continuous high glucose group (MS) and hyperglycemia group (MF). MF group daily intraperitoneal injection of glucose and subcutaneous injection of insulin caused by blood glucose fluctuation model, MS group daily intraperitoneal glucose injection caused a sustained high blood sugar model, NC group daily intraperitoneal injection of equal dose of saline for 6 weeks, daily observation General signs of rats. The rats were subjected to behavioral tests at week 6, including Morris water maze test and Y maze test; at the end of the sixth week, blood glucose was measured at 9 time points throughout the day. Anesthetized rats, the heart blood, serum TC and TG content. The brain was decapitated and the hippocampus was separated. The changes of hippocampal pathological changes and neurons were observed by HE staining and toluidine blue staining. RT-PCR and immunohistochemistry were used to detect the expression of Ghrelin and GHSR1a mRNA and protein in hippocampus. Results Compared with NC group, the body weight growth rate, the content of TC and TG in MS group and MF group were increased (P <0.05 or P <0.01), the cognitive decline, pathological changes of hippocampus and neurons were serious. The levels of Ghrelin, Compared with MS group, the changes of TC, cognitive function, pathological changes of hippocampus, Ghrelin and GHSR1a protein expression in MF group were more obvious than those in MS group (P <0.05 or P <0.01) P <0.01). Conclusions The expression of Ghrelin and GHSR1a in the hippocampus of diabetic rats is decreased, which plays an important role in accelerating the pathogenesis of diabetic encephalopathy.