粉防己碱预处理减轻大鼠肝脏缺血再灌注损伤的机制研究(1)
【摘要】 目的 研究粉防己碱(tetrandrine,TET)预处理对大鼠肝缺血再灌注损伤的预防作用及其机制。方法 大鼠肝脏左中叶缺血50 min，再灌注24 h后处死(I/R组)，TET+I/R组缺血前30 min腹腔注射TET(50 mg/kg)，余同I/R组。大鼠处死前采血检测丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),乳酸脱氢酶(LDH),取缺血肝组织进行超氧化物歧化酶(SOD),一氧化氮(NO)，丙二醛(MDA)，湿重干重(W/D)比检测和组织学检查。结果 I/R组血清ALT,AST和LDH升高，组织MDA水平,W/D比值也明显升高，SOD活性和NO含量下降。在TET+I/R组，血清ALT,AST,LDH，以及组织W/D比值较I/R组降低，SOD活性和NO含量升高。此外，TET+I/R组大鼠血清ALT,AST,组织MDA 和W/D比值较假手术组升高，SOD活性和NO含量降低.组织学检查显示TET+I/R组肝损害减轻。结论 TET能减轻但不能防止肝I/R损伤的发生，减少脂质过氧化物产生是TET抗I/R损伤的原因之一。
, 百拇医药
【关键词】粉防己碱；缺血再灌注；大鼠
Effect of pharmacologic preconditioning with tetrandrine on subsequent ischemia/reperfusion injury
in rat liver
LIU Zhong-min,XIONG Jin-wen,LIN Zhi-min,et al.Longgang People’s Hospital of Shenzhen,Guangdong 518172,China
【Abstract】 Objective The effect of tetrandrine(TET)pretreatment of Wistar rats subjected to warm hepatic ischemia/reperfusion(I/R)was investigated.Metheds After 50 minutes of ischemia in the left and median lobes of the liver and 24 hours of reperfusion(I/R group),the rats were killed.The TET+I/R group rats were pretreated with TET(50 mg/kg body weight IP)30 minutes prior to the onset of ischemia.Blood samples were taken for measurement of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH).Tissue was taken from the ischemic lobes for measurement of superoxide dismutase(SOD),malonyldialdehyde(MDA),and myeloperoxidase(MPO); determination of the wet/dry weight(W/D)ratio; and histologic studies.Results The results showed that ALT,AST,and LDH levels in serum were increased in the I/R group; tissue MDA generation,MPO activity,and the W/D ratio were also increased,accompanied by decreased SOD activity.The serum ALT,AST,and LDH levels,as well as the tissue MPO level and W/D ratio,were lower in the TET+I/R group than in the I/R group; and the SOD level was higher in the TET+IR group than in the I/R group.Moreover,the serum ALT and AST,tissue MDA,and W/D ratio in the TET+I/R group were higher,and the SOD was lower than in the sham group.The histologic examination showed protection against liver damage in the TET+I/R group.Conclusion The results demonstrated that pretreatment with TET could somewhat protect the liver against I/R injury but does not prevent it.The simultaneous decrease of both lipid peroxide generation and polymorphonuclear neutrophil infiltration in the ischemic liver may explain the acquisition of tolerance following administration of TET.
, 百拇医药
【Key words】Tetrandrine; Ischemia reperfusion; Rat
粉防己碱(tetrandrine,TET)是千金藤属防己科植物粉防己的主要活性成分，属双苄基异喹啉类。近年来国内外对TET药理作用机制进行了较为广泛的研究，表明TET具有抗缺血再灌注损伤[1-3]，但其确切机制尚不清楚。本文在体内研究TET对肝I/R损伤的保护作用，并探讨其可能机制，现报告如下。
1 材料和方法
1.1 材料 雄性Wistar大鼠15只，体质量180~200 g，购于山东省实验动物中心。实验前自由进食水。TET粉剂购于江西彭泽制药厂，纯度>98%。TET溶于1 N盐酸，用5 N 的NaOH调整pH值至7.4，贮存浓度为10 mg/ml。
1.2 实验方案 大鼠术前禁食1夜，腹腔注射戊巴比妥钠(30 mg/kg)麻醉，开腹，游离肝脏左中叶肝动脉和门静脉分支，以无创伤微动脉夹阻断50 min。其余肝叶肝动脉和门静脉血液供应以及小肠静脉不受影响，以防小肠静脉压升高。再灌注自移除血管夹开始。切口分层缝合，皮下注射丁丙诺啡(0.2 mg/kg)止痛。TET+I/R组大鼠缺血前30 min腹腔注射TET(50 mg/kg)，假手术组和I/R组大鼠给予生理盐水(5 ml/kg)。假手术组大鼠只开腹进行游离血管手术而不阻断血管。再灌注后24 h处死大鼠，取血用全自动生化分析仪检测丙氨酸氨基转移酶(ALT)，天门冬氨酸氨基转移酶(AST)，乳酸脱氢酶(LDH)活性。同时取缺血肝组织两块，一, http://www.100md.com(刘忠民 熊进文 林智敏 徐振萍 沈文律)
, 百拇医药
【关键词】粉防己碱；缺血再灌注；大鼠
Effect of pharmacologic preconditioning with tetrandrine on subsequent ischemia/reperfusion injury
in rat liver
LIU Zhong-min,XIONG Jin-wen,LIN Zhi-min,et al.Longgang People’s Hospital of Shenzhen,Guangdong 518172,China
【Abstract】 Objective The effect of tetrandrine(TET)pretreatment of Wistar rats subjected to warm hepatic ischemia/reperfusion(I/R)was investigated.Metheds After 50 minutes of ischemia in the left and median lobes of the liver and 24 hours of reperfusion(I/R group),the rats were killed.The TET+I/R group rats were pretreated with TET(50 mg/kg body weight IP)30 minutes prior to the onset of ischemia.Blood samples were taken for measurement of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH).Tissue was taken from the ischemic lobes for measurement of superoxide dismutase(SOD),malonyldialdehyde(MDA),and myeloperoxidase(MPO); determination of the wet/dry weight(W/D)ratio; and histologic studies.Results The results showed that ALT,AST,and LDH levels in serum were increased in the I/R group; tissue MDA generation,MPO activity,and the W/D ratio were also increased,accompanied by decreased SOD activity.The serum ALT,AST,and LDH levels,as well as the tissue MPO level and W/D ratio,were lower in the TET+I/R group than in the I/R group; and the SOD level was higher in the TET+IR group than in the I/R group.Moreover,the serum ALT and AST,tissue MDA,and W/D ratio in the TET+I/R group were higher,and the SOD was lower than in the sham group.The histologic examination showed protection against liver damage in the TET+I/R group.Conclusion The results demonstrated that pretreatment with TET could somewhat protect the liver against I/R injury but does not prevent it.The simultaneous decrease of both lipid peroxide generation and polymorphonuclear neutrophil infiltration in the ischemic liver may explain the acquisition of tolerance following administration of TET.
, 百拇医药
【Key words】Tetrandrine; Ischemia reperfusion; Rat
粉防己碱(tetrandrine,TET)是千金藤属防己科植物粉防己的主要活性成分，属双苄基异喹啉类。近年来国内外对TET药理作用机制进行了较为广泛的研究，表明TET具有抗缺血再灌注损伤[1-3]，但其确切机制尚不清楚。本文在体内研究TET对肝I/R损伤的保护作用，并探讨其可能机制，现报告如下。
1 材料和方法
1.1 材料 雄性Wistar大鼠15只，体质量180~200 g，购于山东省实验动物中心。实验前自由进食水。TET粉剂购于江西彭泽制药厂，纯度>98%。TET溶于1 N盐酸，用5 N 的NaOH调整pH值至7.4，贮存浓度为10 mg/ml。
1.2 实验方案 大鼠术前禁食1夜，腹腔注射戊巴比妥钠(30 mg/kg)麻醉，开腹，游离肝脏左中叶肝动脉和门静脉分支，以无创伤微动脉夹阻断50 min。其余肝叶肝动脉和门静脉血液供应以及小肠静脉不受影响，以防小肠静脉压升高。再灌注自移除血管夹开始。切口分层缝合，皮下注射丁丙诺啡(0.2 mg/kg)止痛。TET+I/R组大鼠缺血前30 min腹腔注射TET(50 mg/kg)，假手术组和I/R组大鼠给予生理盐水(5 ml/kg)。假手术组大鼠只开腹进行游离血管手术而不阻断血管。再灌注后24 h处死大鼠，取血用全自动生化分析仪检测丙氨酸氨基转移酶(ALT)，天门冬氨酸氨基转移酶(AST)，乳酸脱氢酶(LDH)活性。同时取缺血肝组织两块，一, http://www.100md.com(刘忠民 熊进文 林智敏 徐振萍 沈文律)