Agitation of peroxisome proliferator activated receptor β/δ by GW0742 protected against germinal matrix hemorrhage in neonatal rats
Objective:To investigate the neuroprotective effect of GW0742 through activating peroxisome proliferator activated receptor β/δ against germinal matrix hemorrhage in neonatal rats and to explore its mechanism of action.Methods:Seven-day-old rat pups were randomly assigned to Sham,GMH,low-,medium-,and high-dose groups according to their body weight.GMH was induced by injection from the dura mater of collagenase(0.3 U)into the right hemispheric germinal matrix,and GW0742 was peritoneally injected 30 min postoperatively.Neurobe-havioral examinations were employed to evaluate the nervous function of SD neonatal rats;brain water content to assess the degree of cerebral oedema;hemoglobin assay to detect cerebral hemorrhage;ferrous ion detection kit to detect the ion contents;HE staining to observe the pathological morphology of brain tissues of SD neonatal rats;and Western blot experiment to detect the expression of transferrin receptor 1(TFR1)and glutathione peroxidase 4(GPX4)protein expression.Results:Compared with group S,group G showed increased time consumption and higher neurological dysfunction scores in the body righting test and the negative geotaxis test(P<0.01,P<0.01,P<0.01),and increased brain water contents,brain blood volume,and brain tissue ferrous iron contents(P<0.01,P<0.01,P<0.01),and significantly destroyed brain tissues,upregulated TFR1 protein expression(P<0.05)and downregulated GPX4 protein expression(P<0.05)were also found.Compared with group G,group L showed decreased time consumption and lower neurological dysfunction scores in the body righting test and the negative geotaxis test(P<0.05,P<0.05,P<0.05),and decreased brain water contents,brain blood volume,and brain tissue ferrous iron contents(P<0.05,P<0.05,P<0.05);group M showed decreased time consumption and lower neurological dysfunction scores in the body righting test and the negative geotaxis test(P<0.01,P<0.01,P<0.01),and decreased brain water contents,brain blood volume,and brain tissue ferrous iron contents(P<0.01,P<0.01,P<0.01);group H showed decreased time consumption and lower neurological dysfunction scores in the body righting test and the negative geotaxis test(P<0.01,P<0.01,P<0.01),and decreased brain water contents,brain blood volume,and brain tissue ferrous iron contents(P<0.01,P<0.01,P<0.01),and reduction of brain tissue damage,downregulated TFR1 protein expression(P<0.05)and upregulated GPX4 protein expression(P<0.01)were also found.Conclusion:Activation of PPARβ/δ by GW0742 indicated neuroprotective effect against germinal matrix hemorrhage in neonatal rats.
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