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  • Title: [Changes of expression of the P38 MAPK and caspase-3 in rat retinal ischemia-reperfusion model and the influence of Nimodipine].
    Author: Fu YH, Xu J, Zhang JS.
    Journal: Zhonghua Yan Ke Za Zhi; 2006 May; 42(5):435-42. PubMed ID: 16762239.
    Abstract:
    OBJECTIVE: To investigate the protective effects of L-type calcium blocker Nimodipine on retinal ischemia-reperfusion of rat and its affect on cell signal transduction system. METHOD: Ninety-five Wistar rats were divided into 4 groups randomly. Group A was normal (blank) control group and included 5 rats; Group B was retinal ischemia-reperfusion (experimental control) group which had 30 rats; Group C was retinal ischemia-reperfusion plus Nimodipine (experimental) group that included 30 rats; and group D was low-pressure irrigation (pseudo-operation) group that had 30 rats. The rat retinal ischemia-reperfusion model was prepared by elevate the pressure of anterior chamber to 110 mm Hg. Five rats were executed at 2, 6, 12, 24 and 72 hours after reperfusion. The specimens were embedded in paraffin, the expression of P38 MAPK and caspase-3 in the retina was evaluated by in situ hybridization and immunohistochemical studies on every time point, respectively. The results were analyzed by Metamorph software, take the average optical density (A) to perform statistical analyses. RESULTS: After retinal ischemia-reperfusion, the expression of P38 MAPK mRNA and caspase-3 were increased. The in situ hybridization signal of P38 was located in retinal ganglion cell layer and inner nuclear layer, there was only little expression in normal retina. In group B, P38 expression increased 6 hours after reperfusion, reached its peak after 12 hours, continued to 24 hour, decreased gradually after 72 hours. In group C, after Nimodipine medication, the expression trend of P38 was similar to group B, but the expression level was lower. Statistical analyze using average optical density as parameter indicated that the difference of expression of P38 MAPK at 6, 12, 24 and 72 hours was statistical significant (P < 0.05) between group B and C, group B and A, group C and A and D. The expression of caspase-3 was similar to that of P38. Two hours after reperfusion, there were scattering positive nucleus in inner nuclear layer; 6 hours later, positive nucleus were located in ganglion cell layer and inner nuclear layer, and reached its peak after 24 hours. In group C, the expression trend of caspase-3 was similar to that of group B, but had less positive cells and showed lighter staining. CONCLUSION: Both P38 MAPK and caspase-3 participate in signal transduction of retinal neurons during retinal ischemia-reperfusion. Nimodipine can protect the retina by means of down-regulate P38 MAPK and caspase-3 expression.
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