中华临床医师杂志(电子版)
中華臨床醫師雜誌(電子版)
중화림상의사잡지(전자판)
CHINESE JOURNAL OF CLINICIANS(ELECTRONIC VERSION)
2013年
4期
1620-1625
,共6页
田金飞%权伟合%向小卫%雷明慧%苗丽霞%付元元%谢莹%韩继媛
田金飛%權偉閤%嚮小衛%雷明慧%苗麗霞%付元元%謝瑩%韓繼媛
전금비%권위합%향소위%뢰명혜%묘려하%부원원%사형%한계원
肺纤维化%硫辛酸%百草枯%NF-κB%转化生长因子β1
肺纖維化%硫辛痠%百草枯%NF-κB%轉化生長因子β1
폐섬유화%류신산%백초고%NF-κB%전화생장인자β1
Pulmonary fibrosis%Thioctic acid%Paraquat%NF-kappaB%Transforming growth factor bata1
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200~260 g),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PQ 50 mg/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LA 100 mg· kg -1· d-1)24只;LA中剂量组(D组,腹腔注射LA 60 mg· kg -1· d-1)24只;LA小剂量组(E组,腹腔注射LA 30 mg· kg-1· d-1)24只;还原型谷胱甘肽( GSH)组( F组,腹腔注射GSH 200 mg· 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3 ml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,水溶性能与细胞液接触,可清除线粒体来源的自由基,减轻肺纤维化,改善肺功能。
目的探討硫辛痠( LA)榦預急性百草枯( PQ)中毒誘導大鼠肺纖維化的機製。方法選擇健康雄性Sprage-Dawley大鼠144隻(2月齡,體重200~260 g),隨機分正常組(A組,24隻)和實驗組(120隻)。 A組給予等量生理鹽水灌胃,實驗組給予PQ 50 mg/kg灌胃誘導大鼠肺纖維化模型。建立模型後依據榦預方法的不同分為五組:PQ組( B組,腹腔註射等量生理鹽水)24隻;LA大劑量組( C組,腹腔註射LA 100 mg· kg -1· d-1)24隻;LA中劑量組(D組,腹腔註射LA 60 mg· kg -1· d-1)24隻;LA小劑量組(E組,腹腔註射LA 30 mg· kg-1· d-1)24隻;還原型穀胱甘肽( GSH)組( F組,腹腔註射GSH 200 mg· kg-1· d-1)24隻。各組再按測試點不同分為4箇亞組,6隻1籠,分彆飼養(以苦味痠染色隨機編號:頸後部1、右前腿2、左前腿3、右後腿4、左後腿5、尾部6)。在第1、7、14及28天測試點取此組肺組織檢測NO、NOS、TGF-β1水平;取大鼠動脈血3 ml測定NF-κB水平。結果(1)各實驗組肺組織NO、NOS、NF-κB在第7天時達到峰值,第14、28天時下降但仍高于A組,其中B組升高最顯著,B組與各箇榦預組在第1、7、14、28天各箇觀察點比較均具有統計學差異(P<0.01);F組與C組各箇觀察點均差異有統計學意義(P<0.05),F組與D組、E組某些觀察點偶有差異,差異不明顯。(2)動脈血TGF-β1水平在第14天時達到峰值,此後開始下降,但仍高于正常對照組,其中B組升高最顯著,B組與LA各劑量組和F組各箇檢測點比較均具有統計學差異( P<0.05);F組與C組差異有統計學意義( P<0.05),F組與D組在第7、14、28天差異有統計學意義( P<0.05);F組與E組在第28天差異有統計學意義,其餘各觀察點無統計學差異( P>0.05)。結論 LA能減輕PQ誘導的肺纖維化,機製可能是其獨特的抗氧化作用,一方麵抑製NF-κB活性,通過NF-κB-NOS-NO信號通路減少氧自由基,抑製氧化應激;一方麵降低TGF-β1錶達,減輕肺纖維化。 LA具有脂溶性和水溶性,脂溶性能抑製細胞膜上的自由基,水溶性能與細胞液接觸,可清除線粒體來源的自由基,減輕肺纖維化,改善肺功能。
목적탐토류신산( LA)간예급성백초고( PQ)중독유도대서폐섬유화적궤제。방법선택건강웅성Sprage-Dawley대서144지(2월령,체중200~260 g),수궤분정상조(A조,24지)화실험조(120지)。 A조급여등량생리염수관위,실험조급여PQ 50 mg/kg관위유도대서폐섬유화모형。건립모형후의거간예방법적불동분위오조:PQ조( B조,복강주사등량생리염수)24지;LA대제량조( C조,복강주사LA 100 mg· kg -1· d-1)24지;LA중제량조(D조,복강주사LA 60 mg· kg -1· d-1)24지;LA소제량조(E조,복강주사LA 30 mg· kg-1· d-1)24지;환원형곡광감태( GSH)조( F조,복강주사GSH 200 mg· kg-1· d-1)24지。각조재안측시점불동분위4개아조,6지1롱,분별사양(이고미산염색수궤편호:경후부1、우전퇴2、좌전퇴3、우후퇴4、좌후퇴5、미부6)。재제1、7、14급28천측시점취차조폐조직검측NO、NOS、TGF-β1수평;취대서동맥혈3 ml측정NF-κB수평。결과(1)각실험조폐조직NO、NOS、NF-κB재제7천시체도봉치,제14、28천시하강단잉고우A조,기중B조승고최현저,B조여각개간예조재제1、7、14、28천각개관찰점비교균구유통계학차이(P<0.01);F조여C조각개관찰점균차이유통계학의의(P<0.05),F조여D조、E조모사관찰점우유차이,차이불명현。(2)동맥혈TGF-β1수평재제14천시체도봉치,차후개시하강,단잉고우정상대조조,기중B조승고최현저,B조여LA각제량조화F조각개검측점비교균구유통계학차이( P<0.05);F조여C조차이유통계학의의( P<0.05),F조여D조재제7、14、28천차이유통계학의의( P<0.05);F조여E조재제28천차이유통계학의의,기여각관찰점무통계학차이( P>0.05)。결론 LA능감경PQ유도적폐섬유화,궤제가능시기독특적항양화작용,일방면억제NF-κB활성,통과NF-κB-NOS-NO신호통로감소양자유기,억제양화응격;일방면강저TGF-β1표체,감경폐섬유화。 LA구유지용성화수용성,지용성능억제세포막상적자유기,수용성능여세포액접촉,가청제선립체래원적자유기,감경폐섬유화,개선폐공능。
Objective To explore possible protection mechanisms of α-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 group(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,200 mg· kg-1· d-1,peritoneal injection).At the commencement of the experiment ,arterial blood was taken about 3 ml to determine NF-κB,and the levels of NO,NOS,TGF-β1 were tested,which were measured at 1th, 7th,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,7th,14th 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 ( P<0.01 );compared with GSH group ,big dose LA group showed up significant difference (P <0.01),in LA dose group of 7th,14th,in 28th day showed significant difference ( P<0.05 );the level of TGF-β1 in the small dose LA group had significant difference at the 28th day,other than the others checkpoints (P>0.05).Conclusions The results showed that PQ-induced pulmonary fibrosis can be alleviated by LA;the mechanism is possible related to its unique antioxidation .On one hand,LA can reduce NF-κB activity and scavenge oxygen free radicals by NF-κB-NOS-NO signal pathway to inhibit oxidative stress;on the other hand,it can inhibit the expression of TGF-β1,and to alleviate lung tissues fibrosis.LA shows the characteristics of fat-soluble and water-soluble,it is not only scavenging oxygen free radicals in cell membrane ,but also removes the free radicals of mitochondrial origin .Thereby,LA can protect the lung tissues against lung fibrosis .