重组人对氧磷酶K_(192)亚型对毒死蜱中毒所致肺损伤的保护作用  

Protective effect of recombinant human paraoxonase K_(192)(rHuPON1K_(192)) on lung injury induced by chlorpyrifos(CPF) poisoning

作　　者：张娜[1] 韩新飞[1] 张帆[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：《实用药物与临床》2015年第12期1413-1417,共5页Practical Pharmacy and Clinical Remedies

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K_(192)亚型(rHu PON1K192)是否对毒死蜱(CPF)中毒所致SpragueDalwey(SD)大鼠急性肺损伤具有保护作用。方法将健康成年SD雄性大鼠30只随机分为对照组、染毒组、预处理组,每组10只。染毒组大鼠应用毒死蜱以330 mg/kg(2倍LD50)灌胃进行染毒,建立有机磷中毒模型;对照组灌胃等量生理盐水;预处理组于染毒前30 min尾静脉注射r Hu PON1K_(192)(9 000 U/kg)进行预处理。在造模后8 h处死大鼠,采血清和肺组织标本进行检测,测定血清核转录因子-κB(NF-κB)的浓度、超氧化物歧化酶(SOD)、丙二醛(MDA)、肺系数,并观察肺组织病理及电镜变化。结果预处理组与染毒组相比,血清中SOD活力增强,MDA含量减低,肺组织NF-κB活性降低。光镜和电镜下可见对照组大鼠肺组织表现正常。染毒组光镜下可见肺组织出现较重程度粒细胞浸润,肺水肿、肺泡间隔增厚,肺泡内有红细胞聚集,电镜下可见上皮细胞胞质肿胀、鼓泡、破裂,核染色质凝固、碎裂。预处理组大鼠上述改变较轻。结论 rHuPON1K_(192)可以减轻毒死蜱急性中毒大鼠的肺损伤,对肺损伤具有保护作用。Objective To explore whether the recombinant human paraoxonase K_（192）（ r Hu PON1K_（192）） can protect acute lung injury in Sprague-Dalwey（ SD） rats induced by chlorpyrifos（ CPF） poisoning. Methods Thirty healthy male adult SD rats were randomly divided into control group,infected group and pretreatment group,10 rats in each group. Rats in infected group were given chlorpyrifos by gavage 330 mg / kg（ 2 LD50） to establish the organophosphate poisoning model,rats in control group received normal saline,and pretreatment group was given caudal intravenously r Hu PON1K_（192）（ 9 000 U /kg） at 30 min before exposure to chlorpyrifos. The blood and lung tissue samples were collected for testing at 8 h after pretreatment. The serumlevels of nuclear factor-Kappa B（ NF-κB）,Super Oxide Dismutase（ SOD）,malonaldehyde（ MDA） and pulmonary coefficient were determined,and the changes of the lung histopathology and electron microscopy were observed. Results Compared with infected group,the SOD activity in pretreatment group increased,the MDA content in serumand the NF-κB activity of lung tissue decreased. The lung tissue in control group was normal under light microscope and electron microscope,while the tissue appeared heavier degree of neutrophil infiltration,lung edema,alveolar septal thickening and erythrocyte aggregation in alveolar in infected group under light microscope,with swelling,bubbling,cracking of the cytoplasmof the epithelial cells,chromatin coagulation and fragmentation under electron microscopy. The above changes in rats of pretreatment group was lighter. Conclusion r Hu PON1K_（192） can relieve the lung injury of rats with acute chlorpyrifos poisoning,with protective effect on lung injury.

关 键 词：有机磷中毒 毒死蜱 重组人对氧磷酶 急性肺损伤 NF-ΚB 

分 类 号：R595.4[医药卫生—内科学]