硫辛酸干预急性百草枯中毒诱导大鼠肺纤维化的实验研究  

Lipoic acid inhibits the pulmonary fibrosis of rat induced in acute paraquat poisoning

作　　者：田金飞[1] 权伟合[1] 向小卫[1] 雷明慧[1] 苗丽霞[1] 付元元[1] 谢莹[1] 韩继媛[2] 

机构地区：[1]湖北医药学院附属东风医院ICU,湖北十堰442008 [2]华中科技大学附属协和医院急诊科

出　　处：《中华临床医师杂志（电子版）》2013年第4期150-154,共5页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨硫辛酸(LA)干预急性百草枯(PQ)中毒诱导大鼠肺纤维化的机制。方法选择健康雄性Sprage-Dawley大鼠144只(2月龄,体重200～260g),随机分正常组(A组,24只)和实验组(120只)。A组给予等量生理盐水灌胃,实验组给予PQ50mg/kg灌胃诱导大鼠肺纤维化模型。建立模型后依据干预方法的不同分为五组:PQ组(B组,腹腔注射等量生理盐水)24只;LA大剂量组(C组,腹腔注射LA100mg·kg-1·d-1)24只;LA中剂量组(D组,腹腔注射LA60mg·kg-1·d-1)24只;LA小剂量组(E组,腹腔注射LA30mg·kg-1·d-1)24只;还原型谷胱甘肽(GSH)组(F组,腹腔注射GSH200mg·kg-1·d-1)24只。各组再按测试点不同分为4个亚组,6只1笼,分别饲养(以苦味酸染色随机编号:颈后部1、右前腿2、左前腿3、右后腿4、左后腿5、尾部6)。在第1、7、14及28天测试点取此组肺组织检测NO、NOS、TGF-β1水平;取大鼠动脉血3ml测定NF-κB水平。结果 (1)各实验组肺组织NO、NOS、NF-κB在第7天时达到峰值,第14、28天时下降但仍高于A组,其中B组升高最显著,B组与各个干预组在第1、7、14、28天各个观察点比较均具有统计学差异(P<0.01);F组与C组各个观察点均差异有统计学意义(P<0.05),F组与D组、E组某些观察点偶有差异,差异不明显。(2)动脉血TGF-β1水平在第14天时达到峰值,此后开始下降,但仍高于正常对照组,其中B组升高最显著,B组与LA各剂量组和F组各个检测点比较均具有统计学差异(P<0.05);F组与C组差异有统计学意义(P<0.05),F组与D组在第7、14、28天差异有统计学意义(P<0.05);F组与E组在第28天差异有统计学意义,其余各观察点无统计学差异(P>0.05)。结论 LA能减轻PQ诱导的肺纤维化,机制可能是其独特的抗氧化作用,一方面抑制NF-κB活性,通过NF-κB-NOS-NO信号通路减少氧自由基,抑制氧化应激;一方面降低TGF-β1表达,减轻肺纤维化。LA具有脂溶性和水溶性,脂溶性能抑制细胞膜上的自由基,水溶[Abstract] Objective To explore possible protection mechanisms of ct-LA on PQ-induced pulmonary fibrosis. Methods 144 healthy male Sprage-Dawley rats （2 weeks, body weights ranging between 200 and 260 g）, randomly divided into two groups： normal control group （A group, n = 24）and experimental group （n = 120）. Experimental group（50 mg/kg, intragastric administration）was administered to all rats of paraquat. Group A was given to equal dose of saline. Then experimental group can be divided into 5 groups based on the different methods of intervention ：the B groap（n = 24, equal dose of saline, peritoneal injection）, the C group （n = 24, high doses LA, 100 mg· kg-1·d-1 ,peritoneal injection） ,the D group（n =24 ,moderate lipoic acid,60 mg· kg-1·d-1 ,peritoneal injection） ,the E group（n =24,small lipoic acid,30 mg· kg-1·d-1 ,peritoneal injection）and the F group（n =24, glutathione,200mg· kg-1·d-1, peritoneal injection）. At the commencement of the experiment, arterial blood was taken about 3 ml to determine NF-KB, and the levels of NO, NOS,TGF-β1 were tested, which were measured at 1th, 7 2,14th and 28th day after PQ poisoned. Results （ 1 ） The levels of NO, NOS, NF-κB had reached peak at 7th day. It was falling in 14th and 28th day little by little, but it was still higher than normal control group, one of the most significant increase in the PQ group. PQ group compared with each intervention groups at 1th ,72, 142 and 28th each checkpoint, PQ group manifested significant difference（P 〈 0. 01 ） ;Compared GSH group and each dose LA group, LA big dose group of each checkpoint all significant difference （ P 〈 0. 05 ）, LA medium and small dose group had contributed to differences not obvious. （2）The level of TGF-β1 had peak at 14th day,it started to fall later,but it was still higher than normal control group, one of the most significant increase PQ. Compared with each LA groups and GSH group at each checkpoint,PQ group manifested significant deviation（

关 键 词：肺纤维化 硫辛酸 百草枯 NF-κB 转化生长因子Β1 

分 类 号：R595.4[医药卫生—内科学]