去松果体对β-淀粉样蛋白神经毒性的影响

Effects of pinealectomy on the neurotoxicity of amyloid β protein

目的 探讨松果体功能减退致褪黑素 (MT)分泌减少对 β 淀粉样蛋白 (Aβ)神经毒性的影响及其初步机制。 方法 将SD 6周大鼠随机分为 2组 ,实验组摘除松果体 ,对照组给假手术 ,2组均在术后 40d给予Aβ1 4 0 10 μg右侧海马注射 ,7d后标本用Nissl、HE、改进甲醇刚果红染色 ,TUNEL原位标记方法检测海马神经元病理变化。 结果 以图像分析仪测量Nissl染色神经细胞带丢失情况 ,发现实验组丢失长度〔(6 94 6 3± 81 0 9) μm〕明显多于对照组〔(40 6 5 7± 92 38) μm ,P <0 0 1〕 ;细胞凋亡数在HE染色 (16 37± 5 30 )个和TUNEL法 (38 92± 8 81)个均比对照组相应显色方法增多〔分别为 (7 2 9± 2 5 0 )个、(2 0 6 3± 5 2 8)个 ,均为P <0 0 1〕 ;Aβ1 4 0 注射周围的胶质细胞浸润数 (2 76 37±36 33)个也明显多于对照组〔(187 93± 2 1 81)个 ,P <0 0 1〕。 结论 大鼠松果体摘除可以加重Aβ神经毒性作用 ,其机制可能是加重了炎症反应。

Objective To investigate the effects of decreased secretion of melatonin caused by pinealectomy on the neurotoxicity of amyloid β protein (Aβ) and primarily the mechanism. Methods The 6 week old SD rats were randomly divided into two groups. Experimental rats were pinealectomized and the control group was performed by sham operation. Amyloid β protein 1 40 (Aβ 1 40 ) 10 μg in 1μl was injected into the rat hippocampus at the 40th day after operation. The pathological changes of the hippocampus neurons were examined with toluidine blue, haematoxylin eosin, improved Congo red staining and terminal deoxynucleotidyl transferase mediated d UTP biotin nick end labeling (TUNEL) at the 7th day after injection. Results It was showed from the Image Analyser that the Nissl stained depletion in the hippocampus neuron band of the experimental group was significantly wider than that of the control group 〔(694.63±81.09) vs (406.57±92.38)μm, P<0.01〕. The number of apoptotic cells by HE staining and TUNEL method in the pinealectomized rats were increased significantly than that in the control group 〔(16.37±5.30) vs (7.29±2.50)cells/field; (38.92±8.81) vs (20.63±5.28) cells/field, P<0.01〕 respectively. The number of infiltrated glial cells around the injection site in the experimental group were also significantly increased than that of the control group 〔(276.37±36.33) vs (187.93±21.81)cells/field, P<0.01〕 . Conclusions Inflammatory infiltration of glial cells might contribute the mechanism of amyloid β protein neurotoxicity due to pinealectomy.