重组人对氧磷酶1K192亚型对毒死蜱所致SD大鼠急性肝损伤的保护作用  

Protective Effect of the Recombinant Human K192 Subtype of Paraoxonase 1 on Chlorpyrifos-induced Acute Liver Injury in SD Rats

作　　者：张帆[1] 韩新飞[1] 张娜[1] 张鹏思[2] 赵敏[1] 

机构地区：[1]中国医科大学附属盛京医院急诊科,沈阳110004 [2]中国医科大学附属盛京医院社会服务部,沈阳110004

出　　处：《中国医科大学学报》2016年第2期101-105,115,共6页Journal of China Medical University

基　　金：国家自然科学基金(81171793);盛京自由研究者计划

摘　　要：目的探讨重组人对氧磷酶1K192亚型(r Hu PON1K192)对毒死蜱中毒导致的大鼠急性肝脏损伤的保护作用。方法将健康成年SD大鼠50只随机分为正常组(A组)、r Hu PON1K192对照组(B组)、毒死蜱染毒组(C组)、低剂量r Hu PON1K192预处理组(D组)、高剂量r Hu PON1K192预处理组(E组),每组10只。C、D、E组均给予毒死蜱灌胃,D组在灌毒30 min前予以r Hu PON1K192 4 500 U/kg尾静脉注射,E组予以9 000 U/kg r Hu PON1K192尾静脉注射,A组予以与毒死蜱同体积生理盐水灌胃,B组则单纯予以r Hu PON1K192尾静脉注射。8 h后取血,采用速率法检测谷丙转氨酶(ALT)及谷草转氨酶(AST)的活性,采用ELISA法检测苹果酸脱氢酶(MDH)及谷氨酸脱氢酶(GLDH)的活性;取肝脏组织行免疫组化检测缺氧诱导因子1α(HIF-1α)的表达,采用光镜、透射电镜检查超微结构的改变。比较各组之间相关指标的差异。结果比较A组与B组各项指标,差异均无统计学意义(P>0.05)。C组肝功能指标ALT、AST、GLDH及MDH较A组均有明显升高(P<0.01),HIF-1α呈重度表达,电镜与光镜下肝细胞膜、线粒体等出现明显损伤。D组及E组上述指标较A组轻度升高,E组改变程度较D组稍轻,2组各指标相比无统计学差异(P>0.05)。D组及E组上述指标改变较C组轻,差异均有统计学意义(P<0.05)。结论 r Hu PON1K192对毒死蜱中毒肝损伤具有保护作用。Objective To investigate the protective effect of recombinant human K192 subtype of paraoxonase 1 （rHuPON1K192） on acute chlor- pyrifos poisoning induced liver injury in rats. Methods Totally 50 healthy adult SD rats were randomly assigned into five equal groups, including normal group （group A）, rHuPON 1 K192 control group （group B）, ehlorpyrifos group （group C ）, low dose rHuPON1 K192 pretreated group （group D）, and high dose rHuPON1K192 pretreated group （group E ）. Group C, D and E were given intragastric administration of ehiorpyrifos. Group D was given rHuPON1K192 by caudal intravenous injection according to 4 500 U/kg 30 min before intragastric administration of chlorpyrifos. Group E was given rHuPON1K192 according to 9 000 U/kg. Group A received same volume of saline by intragastrie administration. Group B was only given rHu- PON 1 K192 by caudal intravenous injection. After 8 hours, the rats were anesthetized and the blood was harvested. The activity of alanine aminotrans- ferase （ALT） and glutamie-oxalacetic transaminase （AST） was detected by rate method, and the activity of mallc dehydrogenase （MDH） and glutamate dehydrogenase （ GLDH ） was determined by ELISA method. The expression of hypoxia inducible factor- 1α（ HIF- 1α ） in liver tissue was detect- ed by immunohistechemical method. The liver tissue was examined by light microscope and transmission electron microscope （TEM）. Finally the differences among the groups were compared. Results There was no significant difference between group A and group B （P 〉 0.05）. Compared with group A, the liver function indexes of ALT, AST, GLDH and MDH exhibited significant increase in group C, a higher expression of HIF-1α was also observed, and the pathological observation showed severe damage of cell membrane and mitochondrion （P 〈 0.01 ）. The above indexes in group D and group E were slightly elevated compared with group A, the change in group E was smaller than that of group D. There was no significa

关 键 词：SD大鼠 毒死蜱 重组人对氧磷酶1K192 肝损伤 

分 类 号：R575.5[医药卫生—消化系统]