H2受体介导组胺对大鼠海马缺氧缺糖诱导细胞水肿及活性降低的保护作用

目的探讨组胺对海马脑片缺血诱导细胞水肿及活性降低的作用，以及与受体亚型的关系。方法大鼠海马脑片以缺氧缺糖(OGD)诱导缺血损伤后，实时检测CA1区透光度变化评价细胞水肿；并测定2,3,5-三苯基氯化四氮唑(TTC)产物甲，评价脑片活性。观察不同浓度组胺的作用，以及组胺受体拮抗剂对组胺作用的影响。结果 组胺(0.01～10 μmol·L^-1)明显抑制OGD诱导的海马脑片透光度增加，并提高脑片活性。H₁受体拮抗剂苯海拉明(0.1～10 μmol·L^-1)不影响组胺的作用，H₂受体拮抗剂西咪替丁(0.1～10 μmol·L^-1)则部分拮抗组胺的保护作用。结论组胺对大鼠海马脑片缺血诱导细胞水肿及活性降低有保护作用，该作用与H₂受体有关。

H2 receptor mediates the protective effect of histamine against the cellular edema and viability reduction induced by oxygen-glucose deprivation in rat hippocampal slices

AIM: To determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect. METHODS: In vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated. RESULTS: Histamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine. CONCLUSION: Histamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.