| ObjectiveTo observe the effects of Fasudil on survival time,neuroethology and the expression of ROCK and pERM in rats with hypoxic-ischemic brain damage (HIBD) and probe into its mechanism, by intraperitoneal injection of Fasudil in the HIBD model of neonatal rats.MethodsOne hundred and fifty 7-day postnatal SD rats were randomly divided into 3 groups: shamsurgery group (n=50), hypoxic-ischemic brain damage group (n=50) and Fasudil-treated group (n=50). Immediately after hypoxic-ischemic insult, 10mg/kg per rat of Fasudil or 10ml/kg per rat of normal saline solution was injected intraperitoneally once a day for 7 days. The shamsurgery group was not administrated. Every group was divided into two subsets: survival analysis subset (n=10),whose neuroethological performance and survival time were observed; executed subset whose pups were perfused at 6h, 24h, 48h, 3d and 7d of recovery from hypoxic-ischemia. Immunohistochemical technical was applied to investigate the changes of expression of ROCK and pERM in cerebral tissues. Results1. Survival analysis showed: there was non-apparent abnormality with shamsurgery group; in comparison with shamsurgery group, the life span of HIBD group decreased, demonstrating significant difference (p<0.05); in comparison with HIBD group, the life span of Fasudil group increased, but there is no significant difference (p>0.05).2. Neuroethological score showed: there was non-apparent abnormality with shamsurgery group; in comparison with shamsurgery group, the neuroethological score of HIBD group decreased, demonstrating significant difference (p<0.05); in comparison with HIBD group, the neuroethological score of Fasudil group increased, demonstrating significant difference (p<0.05).3. The expression of ROCK protein: shamsurgery group has small amounts of the protein; in comparison with shamsurgery group, the expression of ROCK protein increased markedly in HIBD group, peaked at 24h, demonstrating significant difference at 24h, 48h and 72h (p<0.05); in comparison with HIBD group, ROCK protein decreased markedly in Fasudil group, demonstrating significant difference at 24h, 48h and 72h (p<0.05).4. The expression of pERM protein: shamsurgery group has small amounts of the protein; in comparison with shamsurgery group the expression of pERM protein increased markedly in HIBD group, peaked at 72h ,demonstrating significant difference at 24h, 48h, 72h and 7d (p<0.05); in comparison with HIBD group, pERM protein decreased markedly in Fasudil group, demonstrating significant difference at 24h, 48h, 72h and 7d (p<0.05). Conclusion1. Fasudil can siginificantly improve the neuroethological performance of rats with HIBD including voluntary motor function, capability of emotional behavior and athletic symmetry of limbs.2. The expression of ROCK and pERM protein increased in brains of rats with HIBD, but the peak of pERM is later than ROCK .It suggested that the high level of ROCK protein could accelerate the activation of ERM.3. Fasudil may inhibit ROCK and then inhibit the abnomol activation of ERM by the Rho/ROCK pathway to lessen the inhibiting effects of myelin inhibition factor and glial scar and then promote the restroration of post brain damage in rats with HIBD. |
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