Bai Jian, Wang Yongli
Beijing Drug Administration, Beijing, 100016 China.
Zhonghua Yi Xue Za Zhi. 2002 Aug 25;82(16):1130-2.
To examine the effect of dipfluzine (Dip), a novel calcium channel blocker first developed in China, on acute ischemic brain edema.
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. Except 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.
The water and Na(+) contents in hippocampus of model control group were 77.4% and 279 +/- 22 micro mol/g dry tissue respectively, significantly higher than those in sham operation group (74.8% and 220 +/- 22 micro mol/g dry tissue). The K(+) content in the hippocampus of the model control group was 381 +/- 28 micro mol/g dry tissue respectively, significantly lower than that in the sham operation group (430 +/- 30 micro mol/g dry tissue). The Na(+), K(+)-ATPase activity in the plasmalemma of brain cells in model control group was 179 +/- 62 micro mol pi/mg protein/min, significantly lower than that in sham operation group (1006 +/- 130 micro mol 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 micro mol/g dry tissue and 223 +/- 36 micro mol/g dry tissue respectively, significantly lower than that in model control group (279 +/- 22 micro mol/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 micro mol/g dry tissue and 434 +/- 29 micro mol/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 micro mol 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).
Dip attenuates dose-dependently the increased H(2)O 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.
研究我国自主研发的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。
选用130只沙土鼠，雌雄各65只，体重68±10g。将80只沙土鼠随机分为4组，每组20只：假手术组、Dip 25mg/kg组和Dip 50mg/kg组。120只沙土鼠均腹腔注射不同浓度的溶液或Dip。注射1小时后切开颈部皮肤。除假手术组外，其余70只沙土鼠行双侧颈总动脉结扎（BCAL）以造成脑水肿。另取10只沙土鼠作为正常对照，不进行注射和手术。术后1小时，处死所有动物，取全脑组织检测水、Na⁺和K⁺含量。另取50只沙土鼠的脑组织制备匀浆，测定Na⁺，K⁺-ATP酶活性。
模型对照组海马组织水含量和Na⁺含量分别为77.4%和279±22μmol/g干组织，显著高于假手术组（74.8%和220±22μmol/g干组织）。模型对照组海马组织K⁺含量为381±28μmol/g干组织，显著低于假手术组（430±30μmol/g干组织）。模型对照组脑细胞质膜Na⁺，K⁺-ATP酶活性为179±62μmol Pi/mg蛋白/分钟，显著低于假手术组（1006±130μmol Pi/mg蛋白/分钟，P<0.01）。Dip 25mg/kg组和Dip 50mg/kg组海马组织水含量分别为75.4±0.5%和74.8±0.9%，显著低于模型对照组（均P<0.01）。Dip 25mg/kg组和Dip 50mg/kg组海马组织Na⁺含量分别为2
