系统性炎症对糖尿病小鼠基底节损害的影响及机制

【目的】研究系统性炎症对糖尿病小鼠模型基底节血脑屏障（BBB）破坏、炎性细胞活化和神经元变性的影响及机制。【方法】腹腔注射链尿霉素制备糖尿病小鼠模型，利用脂多糖（LPS）建立系统性炎症，分为糖尿病组、系统性炎症+糖尿病组和对照组，分别检测基底节小胶质细胞、星形胶质细胞活化和神经元变性情况，并检测基质金属蛋白酶（MMPs）活性BBB紧密连接蛋白Occludin表达水平。【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显著减少（P<0.01），系统性炎症糖尿病组基底节神经元数量进一步减少（P<0.01）。糖尿病组小鼠小胶质细胞活化数量明显增加（P<0.01），在系统性炎症时，糖尿病小鼠小胶质细胞活化更加明显（P<0.05）。星形胶质细胞活化的数量在糖尿病组较对照组显著增多（P<0.01），在LPS诱导的系统性炎性反应糖尿病小鼠中，这种改变更加明显（P<0.01）。糖尿病小鼠MMP9较对照组明显活化，而LPS诱导的系统性炎症时糖尿病小鼠MMP9活化更加明显（P<0.05），而MMP2活性没有明显差异。糖尿病小鼠脑内基底节Occludin表达较对照组显著减少，而系统性炎症时，糖尿病小鼠基底节Occludin表达减少更加明显。【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，而系统性炎症加重病理过程。

Effects of systemic inflammation on basal ganglia damage in diabetic mice and the underlying mechanisms

Objective: To study the effects and mechanisms of systemic inflammation on the damage of blood brain barrier (BBB), innate immune cell activations and neuronal degeneration in basal ganglia of diabetic mice.Methods: Diabetic mouse model was established by intraperitoneal injection of Streptozotocin. The system inflammation was induced by i.p. lipopolysaccharide (LPS). The mice were classified as diabetic group, diabetic plus LPS group and control group. The microglia and astrocyte activation, and neuronal degeneration were quantitatively detected in the area of basal ganglia. Matrix metalloproteinase (MMPs) activity was detected and the expression of occludin measured.Results: Compared with control group, the number of neurons in basal ganglia was significantly decreased in the diabetic group (P<0.01), and further reduced in the diabetic plus LPS group (P<0.01). The number of active microglia in the diabetic group was significantly increased compared with control group (P<0.01), and the activation of microglia in diabetic plus LPS group was even more obvious (P<0.05). The number of active astrocytes in the diabetes group was significantly higher than in the control group (P<0.01), and this change was more pronounced in the diabetic plus LPS mice (P<0.01). MMP9 was significantly more activated in diabetic group than the control group, while the MMP9 activity was more pronounced in diabetic plus LPS group (P<0.05) than in diabetic group. However, MMP2 activity was not significantly different among three groups (P>0.05). The expression of Occludin in the basal ganglia was significantly decreased in diabetic group compared with control group, and even more decreased in diabetic plus LPS group than diabetic group.