WEB2170对血小板活化因子所致肝损伤的保护作用

目的研究血小板活化因子（PAF）对肝脏的损伤作用及其拮抗剂WEB2170的预防保护作用。方法体内实验，45只Wistar大鼠随机均分为对照组、PAF损伤组和WEB2170预处理组，测定血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）和肝组织丙二醛（MDA）水平，组化染色积分光密度法测定线粒体琥珀酸脱氢酶（SDH）活性，观察肝组织形态学改变。体外实验，应用DPH探针测定培养肝细胞膜流动性的变化，观察用PAF刺激培养的Kupffer细胞产生肿瘤坏死因子（TNF）和MDA的情况。结果体内实验：PAF可致大鼠血清AST、ALT、LDH及组织MDA升高（P〈0．05～0．01），SDH酶染色积分光密度值（Dλ）降低，WEB2170预处理可减轻上述改变（P〈0．05～0．01）；体外实验，PAF可使肝细胞膜流动性降低（P〈0．01），而WEB2170（50ng／ml）可减轻PAF所导致膜的流动性降低（P〈0．05）；PAF可刺激Kupffer细胞产生TNF、MDA（P〈0．01），呈剂量依赖性，可被WEB2170显著抑制（P〈0．01）。结论PAF对肝脏有损害作用，其拮抗剂WEB2170对PAF所致肝脏损害有一定的保护作用。

Protective effects of WEB2170 on liver damage induced by platelet activating factor (PAF)

Objective To study the liver damage induced by platelet activating factor (PAF) and the protective effects of the PAF antagonist WEB2170. Methods Experiments in vivo: after the administration of PAF to induce liver damage in rats, serum levels of aspartate transaminase (AST), alanine transaminase (ALT), lactic dehydrogenase (LDH) and tissue malonyldialdehyde (MDA) were determined by biochemical method, the succinate dehydrogenase (SDH) activity in mitochondrion was assessed by histochemical method, and the morphologic changes in hepatic structure were observed. In the treatment group, WEB2170 was used for intervention. Experiments in vitro: the fluidity of cellular velum of liver cells was detected with DPH probe, and the effect of TNF and MDA produced by Kupffer cells cultured by PAF stimulation was observed. Results PAF increased the expression of serum AST, ALT, LDH and tissue MDA (P<0.05 or P<0.01). The PAF antagonist WEB2170 partly interdicted the decreasing of SDH activity (P<0.05 or P<0.01). PAF decreased the fluidity of liver cellular velum ( P< 0.01), while WEB2170 (50ng/ml) interdicted such decreasing (P<0.05). PAF stimulated the Kupffer cells to produce TNF and MDA (P<0.01), while such an effect was interdicted by WEB2170. Conclusion PAF is capable to damage the liver. WEB2170 may provide protection in certain extent against such damage.