Jin Dianshi, Sheng Jun, Yang Xinjian, Gao Baoshan
Department of Neurosurgery, ZhongShan Affiliated Hospital of Dalian University, Dalian 116001, China.
Surg Neurol. 2007;68 Suppl 2:S11-6; discussion S16. doi: 10.1016/j.surneu.2007.02.060. Epub 2007 Aug 21.
[corrected] Matrix metalloproteinases and TIMPs are potent elastases and collagenases, which regulate the remodeling of vascular and play an important role in the development of cerebral aneurysm. Until now, little quantitative data regarding MMPs and TIMPs exist.
Tissue samples of cerebral aneurysm were obtained from 30 patients who underwent cerebral aneurysm clipping operation. We used real-time RT-PCR method to quantitatively measure mRNA levels in small tissue samples and determined gene expression levels of MMPs and TIMPs relative to that of GAPDH in each sample. The ELISA method has been used to measure the serum level of MMP-2 and MMP-9 in patients with cerebral ruptured aneurysm and patients with unruptured aneurysm.
Matrix metalloproteinase-2 and MMP-9 were overexpressed in cerebral ruptured aneurysm compared with unruptured aneurysm (4.28 +/- 2.01 vs 0.16 +/- 0.12 [P < .01] and 5.21 +/- 0.87 vs 1.69 +/- 1.00 [P < .05], respectively). The expression levels of MMP-2 to TIMP-1, MMP-2 to TIMP-2, MMP-2 to TIMP-3, and MMP-9 to TIMP-2 were higher in cerebral ruptured aneurysms than in unruptured aneurysms (1.22 +/- 0.53 vs 0.18 +/- 0.05, 4.23 +/- 1.32 vs 0.53 +/- 0.12, 1.69 +/- 0.49 vs 0.18 +/- 0.02, and 7.61 +/- 1.61 vs 2.76 +/- 0.76, respectively; P < .05). Patients with cerebral ruptured aneurysm (n = 15) had higher serum MMP-2 and MMP-9 levels than those with unruptured aneurysm detectable by angiography (n = 15) (1047 +/- 33 vs 110 +/- 26 ng/mL and 1066 +/- 43 vs 120 +/- 27 ng/mL, respectively; P < .02).
The disproportional expression of among MMP-2, MMP-9, and TIMP contribute to the evolution of cerebral aneurysm. Real-time RT-PCR method is suitable for the determination of mRNA levels in small samples of vascular tissue.
[已修正]基质金属蛋白酶和金属蛋白酶组织抑制因子是强效的弹性蛋白酶和胶原酶，它们调节血管重塑，在脑动脉瘤的发展中起重要作用。到目前为止，关于基质金属蛋白酶和金属蛋白酶组织抑制因子的定量数据很少。
从30例行脑动脉瘤夹闭手术的患者中获取脑动脉瘤组织样本。我们使用实时逆转录聚合酶链反应方法定量测量小组织样本中的mRNA水平，并确定每个样本中基质金属蛋白酶和金属蛋白酶组织抑制因子相对于甘油醛-3-磷酸脱氢酶的基因表达水平。酶联免疫吸附测定法已用于测量脑破裂动脉瘤患者和未破裂动脉瘤患者血清中基质金属蛋白酶-2和基质金属蛋白酶-9的水平。
与未破裂动脉瘤相比，基质金属蛋白酶-2和基质金属蛋白酶-9在脑破裂动脉瘤中过度表达（分别为4.28±2.01对0.16±0.12 [P <.01]和5.21±0.87对1.69±1.00 [P <.05]）。脑破裂动脉瘤中基质金属蛋白酶-2与金属蛋白酶组织抑制因子-1、基质金属蛋白酶-2与金属蛋白酶组织抑制因子-2、基质金属蛋白酶-2与金属蛋白酶组织抑制因子-3以及基质金属蛋白酶-9与金属蛋白酶组织抑制因子-2的表达水平高于未破裂动脉瘤（分别为1.22±0.53对0.18±0.05、4.23±1.32对0.53±0.12、1.69±0.49对0.18±0.02以及7.61±1.61对2.76±0.76；P <.05）。脑破裂动脉瘤患者（n = 15）血清中基质金属蛋白酶-2和基质金属蛋白酶-9水平高于血管造影可检测到的未破裂动脉瘤患者（n = 15）（分别为1047±33对110±26 ng/mL和1066±43对120±27 ng/mL；P <.02）。
基质金属蛋白酶-2、基质金属蛋白酶-9和金属蛋白酶组织抑制因子之间的比例失调表达有助于脑动脉瘤的演变。实时逆转录聚合酶链反应方法适用于测定血管组织小样本中的mRNA水平。
