CAJ | 학술논문

目的评价外源性硫化氢对大鼠失血性休克/复苏时急性肺损伤的影响.方法 SPF级成年雄性SD大鼠32只,体重250 ～ 300 g,6～8周龄,采用随机数字表法,将其分为4组(n=8):假手术组(S组)、假手术+外源性硫化氢的供体NaHS组(S+NaHS组)、失血性休克/复苏组(HS/R组)和失血性休克/复苏+ NaHS组(HS/R+ NaHS组).采用股动脉放血的方法制备失血性休克/复苏模型,10min内使MAP降至35 ～ 40 mmHg,持续90 min,然后于60 min内通过输注3倍放血量的乳酸钠林格氏液和放出的全部血液进行复苏.HS/R+NaHS组和S+NaHS组于复苏前即刻腹腔注射NaHS 28μmol/kg.复苏结束后3h时,进行支气管肺泡灌洗,测定支气管肺泡灌洗液(BALF)蛋白、IL-6和TNF-α的浓度;取肺组织,光镜下观察肺组织病理学结果,进行肺损伤评分,测定肺湿重/干重(W/D)比值、髓过氧化物酶(MPO)活性,并进行凋亡细胞计数,测定caspase-3、caspase-8、Bcl-2、Bax和BH3结构域凋亡诱导蛋白抗原(BID)表达.结果与S组比较,HS/R组和HS/R+ NaHS组BALF蛋白、IL-6和TNF-α的浓度、肺损伤评分、W/D比值、MPO活性、细胞凋亡计数升高,肺组织caspase-3、caspase-8、Bax和BID表达上调,肺组织Bcl-2表达下调(P＜0.05),S+ NaHS组上述指标差异无统计学意义(P＞0.05);与HS/R组比较,HS/R+ NaHS组BALF蛋白、IL-6和TNF-α的浓度、肺损伤评分、W/D比值、MPO活性、细胞凋亡计数降低,肺组织caspase-3、caspase-8、Bax和BID表达下调,肺组织Bcl-2表达上调(P＜0.05).结论外源性硫化氢可减轻大鼠失血性休克/复苏时急性肺损伤,其机制与抑制肺组织炎性反应和细胞凋亡有关.
목적 평개외원성류화경대대서실혈성휴극/복소시급성폐손상적영향.방법 SPF급성년웅성SD대서32지,체중250 ～ 300 g,6～8주령,채용수궤수자표법,장기분위4조(n=8):가수술조(S조)、가수술+외원성류화경적공체NaHS조(S+NaHS조)、실혈성휴극/복소조(HS/R조)화실혈성휴극/복소+ NaHS조(HS/R+ NaHS조).채용고동맥방혈적방법제비실혈성휴극/복소모형,10min내사MAP강지35 ～ 40 mmHg,지속90 min,연후우60 min내통과수주3배방혈량적유산납림격씨액화방출적전부혈액진행복소.HS/R+NaHS조화S+NaHS조우복소전즉각복강주사NaHS 28μmol/kg.복소결속후3h시,진행지기관폐포관세,측정지기관폐포관세액(BALF)단백、IL-6화TNF-α적농도;취폐조직,광경하관찰폐조직병이학결과,진행폐손상평분,측정폐습중/간중(W/D)비치、수과양화물매(MPO)활성,병진행조망세포계수,측정caspase-3、caspase-8、Bcl-2、Bax화BH3결구역조망유도단백항원(BID)표체.결과 여S조비교,HS/R조화HS/R+ NaHS조BALF단백、IL-6화TNF-α적농도、폐손상평분、W/D비치、MPO활성、세포조망계수승고,폐조직caspase-3、caspase-8、Bax화BID표체상조,폐조직Bcl-2표체하조(P＜0.05),S+ NaHS조상술지표차이무통계학의의(P＞0.05);여HS/R조비교,HS/R+ NaHS조BALF단백、IL-6화TNF-α적농도、폐손상평분、W/D비치、MPO활성、세포조망계수강저,폐조직caspase-3、caspase-8、Bax화BID표체하조,폐조직Bcl-2표체상조(P＜0.05).결론 외원성류화경가감경대서실혈성휴극/복소시급성폐손상,기궤제여억제폐조직염성반응화세포조망유관.
Objective To evaluate the effects of exogenous hydrogen sulfide on acute lung injury during hemorrhagic shock and resuscitation (HS/R) in rats.Methods Thirty-two SPF adult male rats,weighing 250-300 g,aged 6-8 weeks,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (S group),sham operation + exogenous NaHS group (S + NaHS group),HS/R group and HS/R + NaHS group.HS/R was induced by withdrawing blood from the femoral artery for 10 min.The mean arterial pressure was maintained at 35-40 mmHg for 90 min.The animals were then resuscitated for 60 min with infusion of lactated Ringer's solution 3 times the volume of blood withdrawn and shed blood.NaHS 28μmol/kg was injected intraperitoneally before resuscitation in HS/R + NaHS and S + NaHS groups.At 3 h after the end of resuscitation,the lungs were harvested and bronchoalveolar lavage fluid (BALF) was prepared for determination of protein,IL-6 and TNF-α concentrations.Lungs were removed for examination of pathological changes which were scored and for determination of wet to dry lung weight (W/D) ratio,myeloperoxidase (MPO) activity,cell apoptosis,and expression of caspase-3,caspase-8,Bcl-2,Bax and BH3 interacting-domain death agonist (BID).Results Compared with S group,the protein,IL-6 and TNF-α concentrations in BALF,pathological score,W/D ratio,MPO activity,and the number of apoptotic cells were significantly increased,the expression of caspase-3,caspase-8,Bax and BID was up-regulated,and the expression of Bcl-2 was down-regulated in HS/R and HS/R + NaHS groups,and no significant changes were found in the parameters mentioned above in S + NaHS group.Compared with HS/R group,the protein,IL-6 and TNF-α concentrations in BALF,pathological score,W/D ratio,MPO activity,and the number of apoptotic cells were significantly decreased,the expression of caspase-3,caspase-8,Bax and BID was down-regulated,and the expression of Bcl-2 was up-regulated in HS/R + NaHS group.Conclusion Exogenous hydrogen sulfide can alleviate acute lung injury during HS/R in rats and inhibition of inflammatory responses and cell apoptosis is involved in the mechanism.