Adeli Soheila, Zahmatkesh Maryam, Ansari Dezfouli Mitra
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Electrophysiology Research Center, Neuroscience Institute, Tehran, Iran, Tehran University of Medical Sciences, Tehran, Iran.
Iran Biomed J. 2019 Jul;23(4):262-71. doi: 10.29252/.23.4.262. Epub 2018 Sep 16.
Matrix metalloproteinase-9 (MMP-9) expression has been implicated in molecular mechanisms of neurodegenerative disorders, and its abnormal level has been reported in Alzheimer’s disease (AD). Some protective mechanisms of statins against neurodegeneration might be mediated by the inhibition of MMP-9 expression. Here, we investigated the effect of simvastatin on the hippocampal MMP-9 expression in the context of AD.
We examined the influence of three-week simvastatin (5 mg/kg) administration on hippocampal MMP-9 expression in a rat model of cognitive decline induced by streptozotocin (STZ). Spatial long-term memory and MMP-9 expression were assessed by Morris water maze (MWM) test and quantitative polymerase chain reaction, respectively.
The results showed a decline in the learning and memory in STZ group when compared with the control group. The MMP-9 up-regulated (1.41 ± 0.2 vs. 0.980 ± 0.02, p < 0.05), and cresyl violet staining showed hippocampal cell damage in STZ group compared with the control group. Simvastatin prevented the up-regulation of MMP-9 (1.05 ± 0.05 vs. 1.41 ± 0.2, p < 0.05), improved spatial memory impairment and attenuated hippocampal cell damage. Furthermore, we found a negative correlation (r = 0.77) between MMP-9 expression and cognitive function.
Our findings suggest that the neuroprotective influence of simvastatin in battle to cognitive impairment is mediated in part by the modulation of MMP-9 expression. The reduction of MMP-9 expression in simvastatin-treated animals is in correlation with the improvement of cognitive functions. Understanding the protective mechanism of simvastatin will shed light on more efficient therapeutic modalities in AD.
基质金属蛋白酶-9（MMP-9）的表达与神经退行性疾病的分子机制有关，且据报道其在阿尔茨海默病（AD）中水平异常。他汀类药物对神经退行性变的一些保护机制可能是通过抑制MMP-9的表达介导的。在此，我们研究了辛伐他汀在AD背景下对海马MMP-9表达的影响。
我们检测了连续三周给予辛伐他汀（5mg/kg）对链脲佐菌素（STZ）诱导的认知功能下降大鼠模型海马MMP-9表达的影响。分别通过莫里斯水迷宫（MWM）试验和定量聚合酶链反应评估空间长期记忆和MMP-9表达。
结果显示，与对照组相比，STZ组的学习和记忆能力下降。MMP-9上调（1.41±0.2对0.980±0.02，p<0.05），与对照组相比，STZ组的甲酚紫染色显示海马细胞损伤。辛伐他汀可防止MMP-9上调（1.05±0.05对1.41±0.2，p<0.05），改善空间记忆障碍并减轻海马细胞损伤。此外，我们发现MMP-9表达与认知功能之间呈负相关（r = 0.77）。
我们的研究结果表明，辛伐他汀对认知障碍的神经保护作用部分是通过调节MMP-9表达介导的。辛伐他汀治疗动物中MMP-9表达的降低与认知功能的改善相关。了解辛伐他汀的保护机制将为AD中更有效的治疗方式提供线索。
