| ObjectiveNeonatal hypoxic-ischemic encephalopathy is a common disease in the neonatal period; it is always caused by perinatal asphyxia. Hypoxic plays a core role, which can induce multiple organ dysfunction including damage of myocardial function even heart failure. Recently, insulin like growth factor-1 (IGF-1) is found to play an import-ant role in the pathogenesis of cardiovascular diseases. After hypoxic ischemic brain damage (HIBD), the blood levels of IGF-1 decreased, which closely related with brain injury and neuronal apoptosis, gastrointestinal dysfunction, and many other diseases, so as a means of disease treatment closely watched by the people, but there is rare reports about the effect of IGF-1 on myocardial injury in HIBD. Bcl-2 protein family plays a key role in apoptosis, the content of Bcl-2 and Bax determines the progress of apoptosis, IGF-1 is an important anti-apoptotic factors of intracellular, which through interactions with many intracellular singnaling protein who involved in cell apoptosis, thereby inhibiting cell apoptosis and promote cell survival.In this study, the HIBD model was prepared, exogenous rhIGF-1 was given by intraperitoneal injection. It was observed with the effects of different doses of IGF to Bcl-2 and Bax protein expression and cell apoptosis in HIBD neonatal rat cardiac tissue, the molecular mechanism of IGF myocardial protectison was discussed, to provide effective ways and means in the clinical treatment of myocardial injury after neonatal HIE.Methods1.The HIBD models were established as follows:made a middle neck incision of the newborn 7 days old Wistar rats, isolated and ligated the left common carotid artery, then the HIBD model was made after hypoxia (8% oxygen and 92% nitrogen gas mixture) for 2.5 hours. Changes in animal behavior observed during hypoxia, and myocardial pathological changes were observed by light microscope.2. Determination of cell apoptosis and Bcl-2 and Bax protein expression:40 newborn 7 days old Wistar rats were randomly divided into sham operation group, HIBD group and IGF-1 treatment group, in which intervention group was divided into high, medium and low doses of three groups,8 animals in each group. Intraperitoneal injection immediately after the end of the hypoxic, Bcl-2 and Bax protein expression and myocardial tissue apoptosis 72 hours after administration was observed in the method of immunohistochemical staining and situ detection of apoptosis (TUNEL).Results 1. HE staining and light microscopy findings:sham operation group:myocardial tissue structure and cell-level clear cells with normal morphology and no edema. HIBD group:Disordered arrangement of myocardial cells, the structure is unclear, vague muscle stripes, some cells edema, part of the cell membrane damage, nuclear dissolution disappeared, some nucleus pyknosis and more inflammatory cells between cells.2. Myocardial cell apoptosis:only a very small amount of apoptosis in the sham group, apoptotic cells increased and apoptosis index was significantly higher in the HIBD group, the intervention group decreased apoptosis compared with HIBD group. Difference was not statistically significant (P>0.05) between the sham group and the IGF-1 high-dose treatment group, the other between every two groups were significantly different (P<0.05).3. Bcl-2 protein expression results:Compare with the sham group with low expression of Bcl-2 protein, the expression of Bcl-2 protein is higher in HIBD group, while that is much higher in the IGF-1 group than in the HIBD group. There is no statistic difference between the HIBD group and the group with low doses of IGF-1 (P>0.05).There is significant difference between every other two groups (P<0.05).4. Bax protein expression results:The expression of Bax protein is weak in sham group, that is higher in the HIBD group, while that is lower in the IGF-1 group than in the HIBD group but higher than in the sham group, and which is related with the doses of IGF-1. There is significant difference between every two groups (P<0.05).Conclusion1. Apoptosis of myocardial cells exist after HIBD.2. IGF-1 treatment interventions can reduce the apoptosis of myocardial cells, and correlated with the doses of IGF-1 given.3. IGF-1 inhibited apoptosis of myocardial cells probable by up-regulating anti-apopt-otic protein Bcl-2 expression, down-regulating expression of pro-apoptotic protein Bax, ultimately play a role in myocardial protection. Provide a deeper theoretical basis for the clinical treatment of myocardial injury after neonatal HIE with IGF-1. |
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