Protective effects of sodium oxybate on hypoxia reoxygenation injury of hippocampal slices in rats

Abstract

Abstract: AIM: To study the protective effects of sodium oxybate(SO) on hypoxia reoxygenation injury of hippocampal slices of rats and investigate its protective mechanism SO to ischemic cerebral injury. METHODS: Experimental model of hypoxia reoxygenation injury of hippocampal slices of rats was adopted. Slices were equally divided into seven groups: control group, hypoxia reoxygenation (H R) group, SO1, 10, 100μmol/L group, NCS-382 [γ-hydroxybutyric acid(GHB) receptors antagonist] 100 μmol/L combined with SO100 μmol/L (NCS-382 +SO100) group, NCS-356 (GHB receptors agonist) 100 μmol/L group. LDH release rate and gamma-aminobutyric acid (GABA) and glutamate (Glu) content in incubation fluid of hippocampal slices were measured. Tissue injury in slices was detected by TTC staining method. The Changes of histomorphology by HE staining were observed as well. Changes of intracellular calcium by flow cytometry and the expression of nitric oxide synthase by enzymohistochemistry method were studied. RESULTS: Hypoxia reoxgenation caused an increase in LDH release rate, a decrease in TTC staining, a decline of GABA Glu ratio and tissue injury obviously, while pretreatment with SO was able to reverse the indexes mentioned above(P<0.01). Fluorescence intensity of intracellular calcium and the number of NOS positive neurons in H R group were higher than those in the control group (P<0.01). However, fluorescence intensity of intracellular calcium (P<0.01) in SO100 and NCS-356 groups was lower than that in H R group, were the number of NOS positive neurons was reduced obviously (P< 0.01). Using SO after GHB receptors antagonist NCS-382, fluorescence intensity of intracellular calcium and the number of NOS positive neurons were similar to HR group. CONCLUSION: SO can protect hippocampal slices subjected to hypoxia reoxygenation injury significantly in rats. The protective mechanism of SO may related to the increase of GABA Glu ratio, the reducing of calcium reflux and decrease of NOS activity by activating GHB receptors.

Key words: sodium oxybate, γ-hydroxybutyric acid receptor, hypoxia reoxygenation injury, intracellular calcium, nitric oxide synthase

CLC Number:

YOU Wen-bin, JIANG Xin-ying, MA Xing, GU Shu-ling, DAI Ti-jun. Protective effects of sodium oxybate on hypoxia reoxygenation injury of hippocampal slices in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(1): 51-56.

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