摘要
目的:研究棉酚对2型糖尿病大鼠认知功能的影响,并探讨其作用机制。方法:雄性SD大鼠30只,随机均分成3组:正常组、2型糖尿病组、棉酚治疗组。后2组给予高脂饮食加小剂量(30mg/kg)链脲佐菌素(STZ)诱导2型糖尿病模型,棉酚治疗组(第1-4周按15mg·kg-1.d-1剂量棉酚灌胃,第5-12周按每周15mg·kg-1剂量棉酚灌胃)。用Morris水迷宫测试大鼠行为学;生化检测血糖及ELISA法检测血皮质酮、放免法检测血胰岛素水平;Western blotting方法检测大脑皮层及海马组织11β-羟基类固醇脱氢酶1(11β-HSD1)、糖皮质激素受体(GR)蛋白表达水平;电镜、光镜下观察大脑皮层及海马组织的形态学改变。结果:与正常组比较,糖尿病组大脑皮层及海马神经元可见较明显的核固缩、高尔基体扩张、线粒体水肿,血糖、血皮质酮、血胰岛素水平显著升高(P<0.01),GR蛋白表达明显降低(P<0.05),11β-HSD1蛋白表达呈升高趋势,行为测试潜伏期显著延长(P<0.01),搜索策略明显变差(P<0.01);经棉酚干预后,大脑皮层及海马组织病理改变较轻,血糖、血皮质酮、血胰岛素水平显著降低(P<0.01),GR蛋白表达明显升高(P<0.05),11β-HSD1蛋白表达明显降低(P<0.05),行为测试潜伏期显著缩短(P<0.01),搜索策略显著好转(P<0.01)。结论:棉酚能改善2型糖尿病大鼠的认知功能,可能与降低2型糖尿病大鼠脑内11β-HSD1蛋白、升高GR蛋白水平有关。
AIM： To study the effect of gossypol on the cognitive function of type 2 diabetic rats, and to explore its mechanism. METHODS： Thirty male Sprague - Dawley rats were divided into three groups randomly： normal group, type 2 diabetic group and gossypol treated group. After fed with high - fat diet for 4 weeks, the later two groups were injected with streptozotocin intraperitoneally to establish type 2 diabetic rat model. The animals in gossypel treated group were given gossypol at dosage of 15 mg/kg once per day for 4 weeks by gavage. Since 5th week, the times of gavages were changed into once per week at the same dosage and lasted to 12th week. Learning and memory abilities of rats were assayed with Morris water maze test. The concentration of blood glucose was measured by biochemical method. The levels of serum corticosterone and insulin were detected by enzyme - linked immunosorbent assay and radioimmunoassay, respectively. The protein expressions of 1113 - HSD1 and GR in cerebral cortex and hippocampus were determined by Western blotting. The morphological changes of cerebral cortex and hippocampus were observed under light microscope and transmission electronic microscope, respectively. RESULTS： Compared to normal group, the karyopyknosis, dilation of golgio- some and mitochondria swelling of neuron from cerebral cortex and hippocampus were prominent in diabetic group. The concentrations of blood glucose, serum corticosterone and insulin increased significantly （P 〈0.01 ）. Protein expression of GR decreased （ P 〈 0. 05 ）, 1113 - HSD1 protein tended to increase. Platform searching score was lower （ P 〈 0. 01 ） and escape latency was longer （P 〈 0. 01 ） in diabetic group. After treated with gossypol, the concentrations of blood glucose, serum corticosterone and insulin declined （ P 〈 0. 01 ）. The protein expression of 1113 - HSD1 was decreased （ P 〈 0. 05 ） and GR was increased （P 〈0. 05）. Escape latency was shorter （P 〈0. 01 ） and platform searching score was increased （P 〈 0. 01 ）. CONCLUSION： Gossypol may improve the cognitive function of type 2 diabetic rats. Decreasing the level of 11β - HSD1 and increasing GR protein in the brain may be involved in the mechanism.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第7期1336-1341,共6页
Chinese Journal of Pathophysiology
基金
温州医学院重大资助项目(No.XNK05010)
浙江省科技计划资助项目(No.2007C34003)
关键词
糖尿病
棉酚
海马
受体
糖皮质激素
11Β-羟基类固醇脱氢酶1
Diabetes mellitus
Gossypol
Hippocampus
Receptors, glucocorticoid
11 beta - hydroxysteroid dehydrogenase type 1
