高血压性脑出血患者血肿周围组织基质金属蛋白酶-9和细胞间黏附分子-1的表达及意义

Expression of matrix metalloproteinase-9 and intercellular adhesion molecule-1 in the perihematomal tissues in human hypertensive intracerebral hemorrhage and its significance

目的探讨脑出血后血肿周围组织基质金属蛋白酶-9(MMP-9)和细胞间黏附分子-1(ICAM-1)的表达与脑水肿的关系。方法①解剖39例脑出血后不同时间死亡患者的脑组织,自出血灶边缘向外1～3 cm 及出血灶对侧相应部位的脑组织进行取材,出血灶对侧设为对照组。②采用HE 染色、免疫组织化学技术观察不同时间点出血灶周围 MMP-9与 ICAM-1在脑组织中的表达和变化规律,实验结果应用 SPSS 11.5软件进行统计学分析。结果①脑出血2 h 后出血灶周围血管内皮细胞即有 MMP-9的表达[(1.2±0.8)个/高倍视野],5～10 h 后血肿周围 MMP-9阳性微血管数明显增高[(4.1±0.8)个/高倍视野],45～48 h 达到高峰[(10.6±1.4)个/高倍视野],96～120 h 后逐渐减弱[(5.0±1.1)个/高倍视野],与对照组比较,差异均有统计学意义(P<0.05),360～408 h 接近零表达。对照组没有 MMP-9表达。②脑出血后2 h 出血灶周围血管和神经细胞即有 ICAM-1的表达[(2.1±0.3)个/高倍视野],17～24 h 血肿周围 ICAM-1阳性微血管数开始明显增加[(6.0±1.1)个/高倍视野],72 h 达到高峰[(11.1±0.9)个/高倍视野],168～312 h 后逐渐减弱[(4.1±0.6)个/高倍视野],仍高于对照组(P<0.05)。此外,对侧脑实质内可见少量阳性神经细胞及 ICAM-1阳性微血管。③MMP-9和 ICAM-1之间有明显的相关性。结论脑出血后出血灶周围 MMP-9及 ICAM-1的表达增加,对脑出血后脑水肿的形成可能有促进作用;MMP-9与 ICAM-1之间可能有协同作用。

Objective To investigate the relationship between the expression of matrix metalloproteinase-9 （MMP-9） and intercellular adhesion molecule-1 （ICAM-1） in the perihematomal tissues in human hypertensive intracerebral hemorrhage （ICH） and brain edema formation following ICH. Methods Paraffin-embedded brain tissues of 39 human fatal cases of ICH from the perihematomal tissues, 1-3 cm away from the margin of the hemorrhagic lesion, as well as tissues from the corresponding area at the opposite side as controls, were stained with HE and immunohistochemistry staining. The expressions of MMP-9 and ICAM-1 in the perihematomal tissues were analyzed with the SPSS 11.5 system. Results ① With MMP-9 immunohistochemical staining positive capillaries in the perihematomal tissues were identified at 2 h （ （ 1.2 ± 0. 8）/HP）. The number of MMP-9 positive capillaries began to rise at 5-10 h （ （4. 1 ±0. 8）/HP） reaching the peak at 45-48 h （（10.6 ± 1.4）/HP,P〈0.05）, then gradually dropped at 96-120 h （（5.0± 1.1 ）/HP） to zero at 360-408 h. The expression of MMP-9 was negative in the countralateral brain tissues of the hemorrhagic focus. ②The ICAM-1 positive capillaries and nerve-cells in the perihematomal tissues were identified at 2 h （ （2. 1 ± 0. 3 ）/HP）. The expression of ICAM-1 started to increase significantly at 17- 24 h after ICH（ （6. 0 ± 1.1 ）/HP）, peaked at 72 h （ （ 11.1 ± 0. 9）/HP）and dropped gradually at （ 168- 312） h （（4, 1 ±0. 6）/HP,P 〈0. 05）. Furthermore, there were few positive nerve-cells and capillaries in the countralateral brain tissues of the hemorrhagic focus. ③ There was a positive correlation between MMP-9 and ICAM-1. Conclusions The increased expression of MMP-9 and ICAM-1 after ICH is probably correlated with the brain edema formation in the brain tissues around the hemotoma. MMP-9 possibly has a synergetic effect with ICAM-1 on the secondary brain damage after ICH.