单唾液酸神经节苷脂对急性低压氧脑水肿后MMP9表达的影响

Effect of ganglioside GM1 on expression of MMP9 after acute hypobaric cerebral edema

目的观察单唾液酸四己糖神经节苷脂(GM1)对急性低压氧后基质金属蛋白酶9(MMP9)表达的影响,探讨MMP9在GM1预防低压氧脑水肿中可能的机制。方法 24只雄性C57BL/6小鼠随机分成4组(n=6):分别为对照(control)组、急性低压氧(HH)组、GM1治疗(GM1+HH)组、单纯给药(GM1)组。control组:置于低压氧舱外的常氧舱内;HH组:置于6 000 m海拔模拟舱内24 h;HH+GM1组:连续腹腔注射GM1 3 d(30 mg/kg),最后一次给药后30 min行急性低压氧处理,方法同HH组;GM1组:前期GM1处理同HH+GM1组,后期同control组处理。小鼠在急性低压氧处理24 h后应用免疫荧光和Western blot检测MMP9蛋白表达水平,通过湿重比和伊文思蓝定量评价脑水肿程度。结果 GM1降低急性低压氧24 h后血脑屏障损伤,减少湿重比(P<0.05)和伊文思蓝渗出量(P<0.05),并抑制MMP9表达上调(P<0.05),减弱星形胶质细胞MMP9荧光强度。结论GM1抑制MMP9表达上调,可能参与其预防急性低压氧脑水肿的机制中。

Objective The effect of monosialotetrahexosylganglioside （GM1） on expression of matrix metalloproteinase-9 （MMP9） after acute exposure to hypoxia and hypobaric conditions was investigated. Methods Adult male C57 mice were randomly divided into 4 groups （control, HH, GM1 ＋ HH, GM1, n =6）. Mice in control group were kept under normal atmospheric pressure; mice in HH group were placed in a decompression chamber which simulated the environment of an altitude of 6 030 m ; mice in HH ＋ GM1 group were exposed to acute hypoxia hypobaric after intra-poritoneal administration of GM1 （30 mg/kg/d） for 3 d; mice in GM1 group were kept outside the decompression chamber after intra-peritoneal administration of GM1 （30 mg/kg/d） for 3 d. The expression of MMP9 was analyzed by Western blot and immunofluorescence staining 24 h after acute hypoxia hypobaric. The integrity of the BBB was evaluated by using Evans blue extravasation and wet/dry ratio methods. Results At 24 h after hypoxia hypobaric, the expression of MMP9 in HH group was increased （P 〈0. 05）, and in GM1 ＋ HH group MMP9 level was down-regulated compared with HH group （P 〈0. 05）. GM1 reduced the Evans blue extravasation （P 〈0.05） and wet/dry ratio （P 〈0.05）. Conclusion GM1 plays a significant neuroprotection by suppressing expression of MMP9 after acute hypoxia hypobaric exposure.