摘要
目的本研究通过观察β淀粉样肽(amyloidβpeptide,Aβ)42及神经生长因子(nerve growth factor,NGF)在实验性糖尿病(diabetes mellitus,DM)脑病小鼠海马表达的长时程变化,探讨DM脑病发病的相关机制。方法 64只雄性昆明小鼠采用数字表法随机分为对照组(C组,n=32)和DM组(n=32)。小鼠禁食12 h后,按200 mg/kg腹腔注射新鲜配制的链脲佐菌素,3 d后尾部测非禁食血糖,大于15 mmol/L者为DM模型复制成功。分别在造模后1、4、8及12周应用免疫组织化学染色方法观察C组与DM组小鼠海马CA1区Aβ42及NGF阳性细胞的变化。结果 1)C组小鼠海马CA1区Aβ42阳性细胞数量少,染色浅;而造模后1、4、8及12周DM组小鼠海马CA1区Aβ42阳性细胞数量较C组增多,染色深。细胞计数结果显示,造模后1周,DM组小鼠海马CA1区Aβ42阳性细胞数量14.10±3.60比C组13.20±3.08略有增加,但差异没有统计学意义(P>0.05)。造模后4、8及12周,DM组小鼠海马CA1区Aβ42阳性细胞数量(16.10±3.67,16.20±2.86,17.50±3.10)比C组(11.70±2.54,12.00±2.67,10.80±2.92)明显增加,差异有统计学意义(P<0.01)。2)C组小鼠海马CA1区NGF阳性细胞数量较多,染色深;造模后1、4、8及12周DM组小鼠海马CA1区NGF阳性细胞染色较C组稍浅。细胞计数结果显示,1、4、8及12周DM组小鼠海马CA1区NGF阳性细胞数量相比,差异无统计学意义(P>0.05)。结论 M中期(4周)小鼠海马内Aβ42表达明显增加,并持续至实验终点(DM 12周)。DM小鼠海马内NGF表达在本研究中没有明显变化。Aβ42参与DM小鼠海马神经元的变性过程,在DM脑病的发病机制中发挥重要作用。
Objective To observe the long-term changes in expression of amyloid 13 peptide（ AS） 42 and nerve growth factor（NGF） in the hippocampus of experimental diabetic mice and to explore the mechanism of diabetic encephalopathy. Methods Sixty-four male mice were divided into a control （ C ） group （ n = 32 ） and a diabetic mellitus （ DM ） group （ n = 32 ） randomly. Streptozocin was freshly prepared and injected at 200 mg/kg, i.p. into mice which had been fasted for 12 h. Three days later, blood glucose in a tail-vein sample was determined; a value ≥15 mmol/L was accepted as a successful induction of a diabetic model. The expression changes of Aβ42 and NGF in the hippocampal CA1 region of C group and DM group mice were studied by immunohistochemical staining at the 4 time-points of 1 week, 4 weeks, 8 weeks and 12 weeks after DM models were established. Results 1. There were slightly stained A1342-positive cells in hippocampal CA1 region of C group mice, while more darkly stained Aβ42-positive cells in hippocampal CA1 region were found in DM group mice at the 4 time-points. The numbers of Aβ42-positive cells in hippocampal CA1 region of DM group mice at 1 week（ 14.10±3. 60） increased a little compared with that of C group mice（ 13.20±3.08 ） with no significant difference（P〉0.05 ）, while the numbers of Aβ42-positive cells in the hippocampal CA1 region of DM group mice at 4 weeks, 8 weeks and 12 weeks（ 16.10±3.67, 16.20±2.86,17.50±3.10） increased significantly（ P〈0.01 ） compared with those of C group mice （ 11.70±2.54, 12.00±2.67, 10.80±2.92）. 2. That there were some darkly stained NGF-positive cells in hippocampal CA1 region of C group mice. DM group mice at the 4 time-points also had some NGF-positive cells in hippocampal CA1 region although the staining was a little pale. There were no significant differences between the numbers of NGF-positive cells in the hippocampal CA1 region of DM group mice at the 4 time-pointsand those of group C mice （ P〉0.05 �
出处
《首都医科大学学报》
CAS
2013年第6期851-855,共5页
Journal of Capital Medical University
基金
北京市自然科学基金(7122036)
北京市神经再生修复重点实验室开放课题(2010SJZS02)
脑血管病转化医学北京市重点实验室开放课题(2013NXGZ03)~~
关键词
糖尿病
脑病
海马
β淀粉样肽42
神经生长因子
diabetes mellitus
encephalophathy
hippocampus
amyloid [3 peptide 42
nerve growth factor
