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.
RESULTS: 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).
CONCLUSION: 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.