Effects Of Calcium-Sensing Receptors On Apoptosis In Rat Hippocampus During Hypoxia(?)Reoxygenation

Objectives: To explore the effects of calcium-sensing receptors（CaSR） on apoptosis in rat hippocampus during hypoxia?reoxygenation（H/R）.Methods: After post-culturing of isolated rat hippocampus, the cultures were subjected to H/R, meanwhile gadolinium chloride（Gd Cl₃, agonist of Ca SR） and NPS 2390（antagonists of Ca SR） was added to reperfusion solution. The number of hippocampal neuron, cell proliferation assay and apoptosis rate was determined by inverted microscope, 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide（MTT） and flow cytometer（FCM）.Besides, caspase-3, Bax, cytochrome C（Cyt-c）, extracellular signal-regulated protein kinase（ERK） 1/2, p ERK1/2, P38 and p P38 were analyzed by Western blotting.Results: The hippocampal neuron number and cell viability were significantly decreased after H/R treatment, and were further significantly reduced when co-treatment with Ca SR agonist Gd Cl₃. But the effects of Gd Cl₃ were attenuated by NPS-2390. Whereas, apoptosis rate, the expression level of caspase-3, Bax and Cyt-c were all significantly increased under H/R condition, and was further significantly increased by Gd Cl₃, but were reversed by NPS-2390（P < 0.05）. Moreover, there were no significant differences in expression of ERK1/2, P38 and p P38 among different groups. However, the expression of p ERK1/2 was significantly increased after H/R treatment, but was significantly reduced by NPS 2390（P <0.05）.Conclusion: The results suggest that Ca SR might play significant roles in the induction of hippocampus apoptosis in rat during H/R through phosphorylation of ERK1/2.