哌唑嗪抑制脂多糖诱导的磷脂酶A_2活性及肝细胞内钙离子超载  

Inhibitory effects of prazosin on lipopolysaccharideinduced phospholipase A_2 activity and hepatocytes calcium overload

作　　者：徐勇 涂植光[2] 康格非[2] 

机构地区：[1]深圳市人民医院检验医学部,广东深圳518020 [2]重庆医科大学临床生化教研室,重庆400046

出　　处：《中国危重病急救医学》2001年第4期216-219,共4页Chinese Critical Care Medicine

基　　金：四川省卫生厅科研基金资助项目! (No.960 0 82 )

摘　　要：目的 :研究 α1 肾上腺素受体拮抗剂哌唑嗪对脂多糖 (L PS)诱导的大鼠血清中磷脂酶 A2 活性及肝细胞内钙离子浓度〔Ca2 +〕i超载的抑制及其对内毒素性肝损害的保护作用及机制。方法 :用腹腔注射 L PS(2 mg/ kg)复制急性肝损害模型 ;用哌唑嗪 (4 m g/ kg)灌胃为保护组 ;检测了处置 6小时后各组大鼠肝细胞内〔Ca2 +〕i,2 4小时后血清丙氨酸转氨酶、天冬氨酸转氨酶、乳酸脱氨酶、γ 谷氨酰转肽酶及肝脏病理切片 ;并对各组血清中分泌型磷脂酶 A2 (s PL A2 )活性、前列腺素 E2 (PGE2 )、肿瘤坏死因子 α(TNFα)的含量进行了动态测定。结果 :哌唑嗪明显降低了由 L PS诱导的肝细胞〔Ca2 +〕i升高和肝功能损害 ;减轻了肝细胞坏死程度和炎性浸润 ;同时对 L PS所引起的血清中 s PL A2 、PGE2 和 TNFα的升高均有不同程度的抑制。结论 :哌唑嗪可通过降低 L PS诱导的肝细胞内 Ca2 +超载、减少 TNFα的产生从而抑制 s PL A2 的过度激活及炎症介质的产生 ,对肝脏具有明显的保护作用。Objective: To investigate the mechanism underlying the protective effects of α 1adrenoceptor antagonistprazosin (PRA) on lipopolysacchride (LPS) induced rat hepatic injury.Methods:LPS (2 mg/kg, i.p.) or LPS+PRA (4 mg/kg,i.g.) was administrated to rats.Intracellular free Ca 2+ concentration (〔Ca 2+ 〕i) of liver tissue ,serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),lactate dehydrogenase(LDH),γglutamyltransferase(GGT) levels were measured six hours later, and liver histological examination were performed 24 hours later.The dynamic changes in secretory phospholipase A 2 (sPLA 2)、tumor necrosis factorα(TNFα)、prostag landin E 2(PGE 2) in serum were measured.Results:PRA significantly reduced the LPSinduced hepatocyte 〔Ca 2+ 〕i concentration and serum levels of AST,ALT,LDH and GGT. Histological examination revealed that treatment with PRA could prevent the hepatocyte necrosis and inflammatory infiltration. In addition,PRA significantly decrease the secretory phospholipase A 2(sPLA 2) activity and the production of hepatocyte TNFα and PGE 2 in serum induced by LPS.Conclusions:The protective effects of PRA on acute endotoxic hepatic injury may be mediated by attenuating hepatocyte Ca 2+ overloading and decreasing TNFα formation,subsequently resulting in inhibition of sPLA 2 release and inflammatory mediators production.

关 键 词：Α-肾上腺素受体 钙离子 肝细胞 脂多糖 磷脂酶A2 前列腺素 肿瘤坏死因子 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]