Role of rho kinase in microvascular damage following cerebral ischemia reperfusion in rats.
Role of rho kinase in microvascular damage following cerebral ischemia reperfusion in rats.
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DOI：
10.3390/ijms12021222
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发表时间：
2011-02-18
影响因子：
5.6
通讯作者：
Ding S
中科院分区：
文献类型：
--
作者：
Liu K;Li Z;Wu T;Ding S
Rho激酶（ROCK）是一种众所周知的Rho下游效应物，在各种生理病理过程中起重要作用。在本研究中，我们旨在探讨ROCK与大脑中动脉闭塞（MCAO）和再灌注后大鼠脑微血管损伤的相关性，并阐明微血管损伤的机制。实时定量PCR法检测MCAO模型大鼠ROCK和基质金属蛋白酶9 (MMP9) mRNA水平，免疫荧光法检测层粘连蛋白（Laminin）， Evans Blue法检测血脑屏障（BBB）通透性。我们观察到脑缺血后不同时间点ROCK表达、脑EB含量和层粘连蛋白表达的变化模式相似。统计学分析进一步证实ROCK表达与脑微血管损伤的发生有显著的线性相关。此外，ROCK抑制剂法舒地尔降低脑EB含量，但增加层粘连蛋白表达。这些结果为ROCK介导微血管损伤提供了强有力的证据。此外，我们发现法舒地尔可以显著抑制缺血诱导的MMP9的表达。因此，我们的研究结果表明，ROCK通过上调MMP9促进微血管损伤，并揭示了ROCK是一种有希望的中风治疗靶点。
Rho kinase (ROCK) is a well-known downstream effector of Rho and plays an important role in various physiopathological processes. In this study, we aim to investigate the correlation between ROCK and microvascular damage in rat brain subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and to elucidate the mechanisms underlying the microvascular damage. ROCK and matrix metalloproteinase 9 (MMP9) mRNA levels were determined by real time quantitative PCR, Laminin was detected by immunofluorescence and Blood Brain Barrier (BBB) permeability was examined by Evans Blue (EB) in rat MCAO models. We observed similar patterns of changes in ROCK expression, brain EB content, and Laminin expression at different time points after brain ischemia. Statistical analysis further confirmed a significant linear correlation of ROCK expression with the onset of microvascular damage in brain. Furthermore, the ROCK inhibitor fasudil decreased brain EB content but increased Laminin expression. These results provide strong evidence that ROCK mediates microvascular damage. In addition, we found that fasudil could significantly inhibit MMP9 expression induced by ischemia. Thus, our findings suggest that ROCK promotes microvascular damage by upregulating MMP9 and reveal ROCK as a promising therapeutic target for stroke.
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