| 摘要: |
| 目的 研究系统性炎症对糖尿病小鼠基底节血脑屏障(BBB)破坏、炎性细胞活化和神经元变性的影响及机制。 方法 腹腔注射链脲佐菌素制备糖尿病小鼠模型,利用脂多糖(LPS)建立系统性炎症模型,分为糖尿病组、糖尿病+LPS组和对照组。免疫荧光染色检测基底节小胶质细胞、星形胶质细胞活化情况及BBB紧密连接蛋白Occludin表达水平;甲苯胺蓝染色检测神经元变性情况;明胶底物凝胶酶谱法检测基质金属蛋白酶(MMPs)活性。 结果 与对照组小鼠相比,糖尿病组小鼠基底节神经元的数量减少(P<0.01), 小胶质细胞和星形胶质细胞活化数量增加(P<0.01);而糖尿病+LPS组小鼠基底节神经元数量进一步减少,小胶质细胞和星形胶质细胞活化数量均增加,与糖尿病组相比差异有统计学意义(P<0.05或P<0.01)。 糖尿病组小鼠MMP-9较对照组明显活化,而糖尿病+LPS组小鼠MMP-9较糖尿病组明显活化(P<0.05);3组MMP-2活性差异无统计学意义。糖尿病组小鼠脑内基底节Occludin表达较对照组减少,而糖尿病+LPS组小鼠基底节Occludin表达减少更明显。 结论 高血糖可以导致基底节炎性细胞活化、BBB破坏和神经元变性,而系统性炎症加重这一病理过程。 |
| 关键词: 糖尿病 系统性炎症 基底节变性 小胶质细胞 血脑屏障 |
| DOI：10.3724/SP.J.1008.2015.01370 |
| 投稿时间：2015-08-04修订日期：2015-10-21 |
| 基金项目:浙江省自然科学基金(LY12H09008). |
|
| Effects of systemic inflammation on basal ganglia damage in diabetic mice and the underlying mechanisms |
| WANG Jing-hua,ZHOU Sheng-li,MAO Ling-na,WANG Gui-feng,SONG Zhen-ya* |
(Department of General Practice, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, China
*Corresponding author.) |
| Abstract: |
| Objective To study the effects of systemic inflammation on the damage of blood brain barrier (BBB), innate immune cell activation and neuronal degeneration in basal ganglia of diabetic mice and the related mechanisms. Methods Diabetic mouse model was established by intraperitoneal injection of streptozotocin. The system inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). The mice were divided into diabetic group, diabetic plus LPS group and control group. The activation of microglia and astrocyte in the area of basal ganglia and protein expression of Occludin in BBB were detected by immunofluoresence. Neuronal degeneration was detected by toluidine blue staining, and matrix metalloproteinase (MMPs) activity was detected by gelatin substrate gel zymography. Results Compared with control group, the number of neurons in the basal ganglia was significantly decreased in the diabetic group (P<0.01) and the number of active microglia was significantly increased (P<0.01). Compared with the diabetic group, the diabetic plus LPS group had significantly decreased neurons in the basal ganglia and significantly increased active microglia and astrocytes (P<0.05 or P<0.01). MMP-9 was significantly activated in diabetic group compared with that in the control group, and that in the diabetic plus LPS group was significantly activated compared with that in the diabetic group (P<0.05). However, the MMP-2 activities were not significantly different among the three groups. Occludin expression in the basal ganglia was decreased in the diabetic group compared with control group, and a more greater decrease was found in diabetic plus LPS group. Conclusion Hyperglycemia can lead to inflammatory cell activation in the basal ganglia, BBB damage and neuronal degeneration in mice; and systemic inflammation can aggravate the pathological process in the basal ganglia. |
| Key words: diabetes mellitus systemic inflammation basal ganglia degeneration microglia cells blood-brain barrier |
