Cyclopamine aggravates rat cerebral ischemia-reperfusion injury / 第二军医大学学报

ABSTRACT

Objective To explore the effect of cyclopamine (Cyc) on cerebral ischemia-reperfusion injury in rats. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=20) sham operation group, cerebral ischemia-reperfusion group (Con group) and cerebral ischemia-reperfusion+Cyc group (Cyc group). Cyc (10 mg/kg) or absolute ethyl alcohol was intraperitoneally injected in animals 3 h after cerebral ischemia for 7 d. Neurological deficit was assessed by Longa scale on day 1 and 14 after cerebral ischemia. At 24 h after cerebral ischemia, the cerebral water content, cerebral infaction area, pathological changes and cell apoptosis were evaluated by dry-wet method, 2,3,5-triphenyltetrazolium (TTC) staining, H-E staining and TUNEL method, respectively. Immunochemical method was used to examine the protein expression of NeuN and caspase-3 at 24 h after ischemia and glial fibrillary acidic protein (GFAP) expression on day 14 after ischemia. Results Neurological deficit score, cerebral water content, cerebral infaction area, TUNEL positive cell counting, protein levels of caspase-3 and GFAP in Cyc and Con groups were significantly higher than those in sham operation group (P<0.05), and the above parameters in Cyc group were also significantly higher than those in Con group (P<0.05). NeuN protein expressions in Cyc and Con groups were significantly lower than those in sham operation group (P<0.05), and NeuN protein in Cyc group was also significantly lower than that in Con group (P<0.05). Cellular and interstitial edema, neurocyte deformation, pyknosis and necrocytosis were more severe in Cyc group than in Con group. Conclusion Cyclopamine can aggravate rat cerebral ischemia-reperfusion injury.