Protective Effects Of K_ATP Channel Opener On Neonatal Rat With Hypoxic-ischemic Brain Damage

Background and Objective: Hypoxic-ischemic encephalopathy (HIE) can cause death of neonate and damage of the neural function. ATP-sensitive potassium channels (Katp) exist in all kinds of neuron, which play an important role in the metabolism of cells and some cellular events as synaptic transmission. Many studies had showed that Katp channel opener (KCO) could control Ca²⁺ and glutamic acid in cells and decreased the ischemic damage in brain, but the exact mechanism still remains unclear. Heat shock protein (HSP70) is one of the protective proteins at the early time of ischemia. It can increase the tolerance of neuron to ischemia and help repair the damage of neuron. We studied the brain edema, the changes of neurological function and the expressiones of HSP70 in cerebral cortex after hypoxic-ischemic damage in neonatal rats and also observed the changes of the indexes after using the KCO (cromakalim) or the KATP channel inhibitor (KCI), so as to investigate the protective effect of KCO in hypoxic-ischemic encephalopathy.Materials and Methods: 150 neonatal rats (7 days after birth) were randomly divided into 5 groups: HI group, KCO group; KCI group; sham operation group (S); control group (C). The changes of neurological functionand pathologic morphology with HE staining and the expressiones of HSP70 with immunohistochemistry staining were observed at different times. The percentages of brain water content were measured at 48h after hypoxic-ischemia in 30 neonatal rats.Result: the neurological function in each group at different times: HI group (24h: 1.65±0.^ 48h: 2.60±0.5> 72h:3.25±0.5); KCO group (24h: 2.62±0.9> 48h: 3.25±0.4 , 72h:4.25±0.7); KCI group (24h: 2.10±0.64, 48h: 2.75±0.7 . 72h: 3.30±0.4); S group (24h: 5^ 48h: 5^ 72h:5); C group (24h: 5^ 48h: 5^ 72h: 5). The injury of neurological function in KCO group was significantly improved than that in HI group and KCI group (P<0.05) and brain edema in KCO group were relieved than in HI and KCI group (P<0.05). The expresses of HSP70 in KCO group were higher than those in HI and KCI group.The pathological changes in each group at different times: in HI group, some neurons were pyknosis and some were necrosis and the volume of the neuron became smaller and interstitial edema had happened. In KCO group, the ischemic changes of neuron were lighten .In KCI group, all the effects of KCO were neutralized. There had no ischemic changes in S group and C group.The expressiones of HSP70 in each group at different times :HI group(24h: 16.12±3.7> 48h: 34.87±3.7^ 72h: 33.50±5.2); KCO group(24h:23.50±2.5> 48h: 47.75±6.K 72h: 44.37±5.4); KCI group (24h: 19.50±l^48h: 35.62±3^ 72h:35.25±3.3); S group (24h: 1.12±1.K 48h: 0.57±0^72h:0.32±0.2 ) .There had no expressiones of HSP70 in C group. Theexpressiones of HSP70 in KCO group were significantly increased than those in HI and KCI group (PO.05).The percentage of brain water content in each group at the 48h after hypoxic-ischemia: HI group(left: 90.16±1.0;right: 87.47±0.18;KCO groupGeft: 87.67±0.3;right: 87.12±0.1) ; KCI group (left: 89.67±0.6;right: 87.45±0.2) ; S group (left: 87.02±0.7; right: 87.18±0.2); C group (left: 86.78±0.4;right: 87.17±0.1 ) .The percentage of brain water content in KCO group was significantly lower than that in HI group and KCI group (P<0.05). The percentage of brain water content in HI group and KCI group were obviously higher than that in C group (PO.01).Conclusions:1. Hypoxic-ischemia could cause neurological function damages, serious brain edema, and ischemic pathological changes and increased the expression of HSP70.2. Given the KCO before HI could significantly improve neurological function, lightene brain edema, ischemic pathological changes and enhance the expression of HSP70.3. Given the KCI after given the KCO could neutralize all the effects of KCO above. Neurological function damages, serious brain edema, ischemic pathological changes were significant. The expression of HSP70 was decrease.The results indicated that KCO could improve the expression of HSP70 protein and block cell apoptosis to decrease the injury of brain after hypoxic-ischemia.