The Relationship Between TGF-β₁, Bcl-2 Expression And Apoptosis In Neonatal Rat Brain Following Cerebral Hypoxia-ischemia And The Protective Effect Of GM₁

Purpose: Apoptosis was one of ways that neurons died after Hypoxic-ischemic brain damage (HIBD) . Apoptosis took very important effect on neuronal death in delayed neuronal death (DND). It had been reported that the expression of apoptosis-related gene Bcl-2 was closely associated with neuronal apoptosis. Transforming growth factor- 0 i (TGF-3 i) can regulate neuronal apoptosis by increasing the expression of Bcl-2. Monosialotetrahexosylganglioside (GMi) is the main kind of gangliosides in mammal, which has the important effect on the process of neuronal cell differentiation, growth and proliferation. GM] has cerebral protective effects. But it is not clear what effect TGF- 3 l has in HIBD and the mechanism of drugs of GMi to protect neurons after HIBD. In this study, The sequential changes of the expression of TGF- 3 i, Bcl-2 and neuronal apoptosis following hypoxia-ischemia (HI) in the cerebral cortex and hippocampus of neonatal rat and the effect of intraperitoneal administration with GMi after HIBD were observed so as to investigatethe relationship between the expression of TGF- 3 j, Bcl-2 and neuronal apoptosis in the brain of neonatal rats following HIBD and the mechanism of drugs of GMi to protect neurons in neonatal HIBD. Methods: An animal model of neonatal hypoxic-ischemic brain damage was developed by ligating the unilateral carotid artery of 7-day-old rats and keeping the rats in a hypoxic (80 ml ?L"1 oxygen) environment for 2 hours. ?Model of HIBD group (untreated group) . ㎝odel of GMi treated group. Everyday GM] were injected through abdominal cavity(intraperitoneal administration with GM]) after HIBD in neonatal rats. The rat brain tissues were collected at different time following hypoxia-ischemia. Hematoxylin-eosin ( HE ) staining, Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL) and SP Immunohistochemistry were used to detect neuronal apoptosis, the expression of TGF- 3 i protein and Bcl-2 protein in the cerebral cortex and hippocampus, respectively.Results: 1. The expression of TGF-P i, Bcl-2 and neuronal apoptosis in HIBD group increased significantly, compared with the control group; (D Neuronal apoptosis in the cerebral cortex and hippocampus began at 2 hours after hypoxia-ischemia, peaked at 24 hours after hypoxic-ischemic insult. A few signal could be found in the control group. Neuronal apoptosis at 24 hours after hypoxia-ischemia was more distinct than that in the control group.㏕he expressing of TGF- P i in the cerebral cortex and hippocampus began at 8 hours after hypoxia-ischemia, peaked separately at 12, 48 hours after hypoxic-ischemic insult. No signal could be found in the control group. (3) The expressing of Bcl-2 in the cerebral cortex andhippocampus began at 2 hours after hypoxia-ischemia, peaked at 48 hours after hypoxic-ischemic insult. No signal could be found in the control group.2. Positive cells of neuronal apoptosis detected by TUNEL in GMi treated group decreased significantly, compared with HIBD group (untreated group) . GMi treatment relieved brain injury and decreased neuronal apoptosis in the cerebral cortex and hippocampus. It is suggested that intraperitoneal administration with GMi has cerebral protective effects on neonatal HIBD. It is no significant difference between the expression of TGF- P i and Bcl-2 in GMj treated group and those in the untreated group. Conclusion: These results indicate that1. The expression of TGF- ?i, Bcl-2 and neuronal apoptosis increased significantly after HIBD, It suggests that the increase in TGF- 3i and Bcl-2 expression could be induced by neonatal hypoxia-ischemia, Implicating that TGF- & ] and Bcl-2 may regulate the process of neuronal apoptosis and play very important role in preventing neurons from injury following cerebral hypoxia-ischemia.2. Both of TGF- 3 i and Bcl-2 expression peaked at 48 hours after hypoxic-ischemic insult, Neuronal apoptosis peaked at 24 hours after hypoxia-ischemia. TGF- P i can regulate neuronal apoptosis by increasing the...