双苯氟嗪对沙土鼠急性脑缺血性脑水肿的影响

Effect of dipfluzine on acute ischemic brain edema in gerbils

目的 探讨新型钙通道阻滞剂双苯氟嗪 (Dip)对急性缺血性脑水肿的作用及机制。方法 选取 1 30只沙土鼠 ,随机分为假手术组、模型对照组、Dip 2 5mg/kg和 50mg/kg组 ,每组 2 0只。行双侧颈动脉结扎 (BCAL) ,制备沙土鼠急性全脑缺血模型。各组动物分别腹腔注射溶剂或不同剂量的Dip ,观察对脑组织Na+ 、K+ 和水含量及Na+ 、K+ ATP酶活性的影响。结果 BCAL后沙土鼠脑组织中的Na+ 和水含量显著高于假手术组 ,K+ 含量及Na+ 、K+ ATP酶活性则显著低于假手术组 ;Dip 2 5和50mg/kg组呈剂量依赖性改变 ,急性脑缺血所致的沙土鼠脑组织K+ 含量及Na+ 、K+ ATP酶活性降低(r=0 9981 )和Na+ 及水含量升高 ,差异有显著意义 (P <0 0 5或 0 0 1 ) ,且脑组织水含量与Na+ 、K+ ATP酶活性变化呈明显负相关 (r=- 0 9997,P <0 0 1 )。

Objective To examine the effect of dipfluzine (Dip), a novel calcium channel blocker first developed in China, on acute ischemic brain edema. Methods One hundred and thirty gerbils, 65 males and 65 females, weighing 68±10 g, were used. Eighty gerbils randomly divided into four groups of 20 animals: sham operation group, Dip 25 mg/kg group, and Dip 50 mg/kg group. All of the 120 gerbils were injected with solution or Dip at different concentrations intraperitoneally. The skin of neck was incised one hour after injection. Exceopt in the sham operation group,bilateral carotid artery ligation (BCAL) was performed in the other 70 gerbils to cause brain edema. Another 10 gerbils were used as normal controls without undergoing injection and operation. One hour after the operation, all of the animals were killed and the whole brain tissue was taken to detect the water and Na + and K + contents. The brain tissues of other 50 gerbils were used to produce homogenate to determine the Na +?K + ATPase activity. Results The water and Na + contents in hippocampus of model control group were 77 4% and 279±22 μmol/g dry tissue respectively, significantly higher than those in sham operation group (74 8% and 220±22 μmol/g dry tissue). The K + content in the hippocampus of the model control group was 381±28 μmol/g dry tissue respectively, significantly lower than that in the sham operation group (430±30 μmol/g dry tissue). The Na +?K + ATPase activity in the plasmalemma of brain cells in model control group was 179±62 μmol pi/mg protein/min, significantly lower than that in sham operation group (1006±130 μmol pi/mg protein/min, P <0 01). The water contents of hippocampus in Dip 25 mg/kg group and Dip 50 mg/kg group were 75 4±0 5% and 74 8±0 9% respectively, significantly lower than that in model control group (all P <0 01). The Na + contents in hippocampus of Dip 25 mg/kg group and Dip 50 mg/kg group were 235±39 μmol/g dry tissue and 223±36 μmol/g dry tissue respectively, significantly lower than that in model control group (279±22 μmol/g dry tissue, all P <0 01). The K + content in hippocampus of Dip 25 mg/kg group and Dip 50 mg/kg group were 427±32 μmol/g dry tissue and 434±29 μmol/g dry tissue respectively, significantly higher than that in model control group ( P <0 05 and P <0 01). The Na +?K + ATPase activity in the plasmalemma of brain cells in Dip 25 mg/kg group and Dip 50 mg/kg group was 649±45 and 1 198±218 μmol pi/mg protein/min respectively, significantly higher than that in model control group ( r =0 9981, P <0 01). The correlation between brain water content and Na +?K + ATPase activity was significant ( r =-0 999 7, P <0 01). Conclusion Dip attenuates dose dependently the increased H 2O and Na + contents, prevents the decrease in potassium level, and accelerates the restoration of lowered Na +?K + ATPase activity resulted from cerebral ischemia, thus preventing ischemic brain edema.