Abstract：
The inhibition of matrix metalloproteinases (MMPs) has shown potential in the treatment of various neurodegenerative diseases, and perioperative neurocognitive disorders (PND) is accompanied by the increased expression of MMP-2 and MMP-9 in the hippocampus. However, the effect of inhibiting MMP-2 and MMP-9 on PND is not clear. In this study we aimed to evaluate the effects of inhibiting MMP-2 and MMP-9 on cognitive function in the aged mice after surgery, in order to find a possible target for the prevention and treatment of PND METHODS: In this study, 14-month-old C57BL/6 mice were used to establish a PND model by tibial fracture surgery and sevoflurane anesthesia. Three days later, part of the mice were subjected to cognitive assessment and the other was sacrificed for biochemical analysis. We used the Novel object recognition test and Fear conditioning test to evaluate the postoperative cognitive function of mice. The expression of mmp-2 and MMP-9 was detected by western blotting. We also examined the expression of claudin-5 and occludin using Western blotting, and the activation of microglia and astrocytes using immunofluorescence.
The results showed that surgery increased the expression of MMP-2 and MMP-9 in the hippocampus of mice, accompanied by cognitive impairment, decreased expression of claudin-5 and occludin, and increased activation of microglia and astrocytes. However, inhibition of MMP-2 and MMP-9 expression by SB-3CT reversed these changes.
Our study shows that inhibition of MMP-2 and MMP-9 alleviates anesthesia/surgery-induced cognitive decline by increasing BBB integrity and inhibiting glial cell activation.
The results showed that surgery increased the expression of MMP-2 and MMP-9 in the hippocampus of mice, accompanied by cognitive impairment, decreased expression of claudin-5 and occludin, and increased activation of microglia and astrocytes. However, inhibition of MMP-2 and MMP-9 expression by SB-3CT reversed these changes.
Our study shows that inhibition of MMP-2 and MMP-9 alleviates anesthesia/surgery-induced cognitive decline by increasing BBB integrity and inhibiting glial cell activation.
摘要：
背景：抑制基质金属蛋白酶（MMPs）在治疗各种神经退行性疾病中显示出潜在的潜力，围手术期神经认知障碍（PND）伴有海马MMP-2和MMP-9表达增加。然而,抑制MMP-2和MMP-9对PND的作用尚不清楚。在这项研究中，我们旨在评估抑制MMP-2和MMP-9对老年小鼠术后认知功能的影响。为了找到预防和治疗PND的可能目标方法：在这项研究中，采用14月龄C57BL/6小鼠通过胫骨骨折手术和七氟醚麻醉建立PND模型。三天后,部分小鼠接受认知评估,另一部分处死进行生化分析.我们用新颖物体辨认试验和恐惧调理试验评价小鼠术后认知功效。免疫印迹法检测MMP-2和MMP-9的表达。我们还使用Western印迹检查了claudin-5和occludin的表达，以及使用免疫荧光激活小胶质细胞和星形胶质细胞。
结果：结果表明，手术增加了小鼠海马中MMP-2和MMP-9的表达，伴有认知障碍，claudin-5和occludin的表达降低，并增加小胶质细胞和星形胶质细胞的激活。然而,SB-3CT对MMP-2和MMP-9表达的抑制作用逆转了这些变化。
结论：我们的研究表明，抑制MMP-2和MMP-9可以通过增加BBB完整性和抑制胶质细胞活化来减轻麻醉/手术引起的认知功能下降。
结果：结果表明，手术增加了小鼠海马中MMP-2和MMP-9的表达，伴有认知障碍，claudin-5和occludin的表达降低，并增加小胶质细胞和星形胶质细胞的激活。然而,SB-3CT对MMP-2和MMP-9表达的抑制作用逆转了这些变化。
结论：我们的研究表明，抑制MMP-2和MMP-9可以通过增加BBB完整性和抑制胶质细胞活化来减轻麻醉/手术引起的认知功能下降。
