气道给rhSOD对胎粪诱导肺损伤中NF-κB及MIP-1α表达的影响

Effect of rhSOD on pulmonary nuclear factor-kappa B and MIP-1α expression in meconium-induced acute lung injury

目的:观察早期经气道给予重组人超氧化物歧化酶(rhSOD)对胎粪诱导大鼠肺NF-κB和炎症因子MIP-1α表达的影响,以探讨其在胎粪诱导肺损伤中的作用及其机制。方法:24只雄性SD大鼠,随机分为:(1)对照组(control),经气管插管注入生理盐水1mL/kg;(2)胎粪+生理盐水处理组(Mec/saline);(3)胎粪+rhSOD治疗组(Mec/rhSOD)。后两者先由气管插管注入20%新生儿胎粪生理盐水混悬液1mL/kg建立急性肺损伤模型,再分别经气管插管注入生理盐水1mL/kg或rhSOD20g.L-1.kg-1。24h后取材,RT-PCR法测定肺组织MIP-1αmRNA、Westernblotting法测定NF-κB蛋白表达改变,同时行支气管肺泡灌洗液(BAL)细胞计数。结果:Mec/saline组大鼠BAL细胞计数、肺组织MIP-1αmRNA和NF-κB蛋白表达均明显高于control组[(4.68±1.40)×109cells/Lvs(0.53±0.19)×109cells/L,3.60±0.75vs1.56±0.33,0.72±0.31vs0.23±0.21],(均P<0.01);Mec/rhSOD组大鼠BAL细胞计数、肺组织MIP-1αmRNA和NF-κB蛋白表达分别为(3.13±0.77)×109cells/L、2.20±0.39和0.44±0.21,均显著低于Mec/saline组(均P<0.01),但仍显著高于control组(均P<0.01)。结论:早期经气道给rhSOD可能通过抑制肺MIP-1α和NF-κB表达而减轻胎粪诱导的肺炎症反应。

AIM： To evaluate the role and mechanisms of recombinant human superoxide dismutase （rhSOD） in meconium- induced acute lung injury. （ALI） by evaluating pulmonary MIP- 1α and NF - κB expression. METHODS： 24 health male Sprage - Dawley rats were randomized to 3 groups （8, each group）, followed by intratracheal （IT） administration with （1） saline at 1 mL/kg （control group）; （2） 20% human newborn meconium suspension at 1 mL/kg, followed by aline at 1 mL/kg （Mec/ saline group） ; （3） 20% human newborn meconium suspension at lmL/kg, followed by rhSOD at 20 mg/kg （Mec/rhSOD group）. The animal was killed 24 h after treatment. The measurements included the bronchoalveolar lavage （BAL） cell count, RT- PCR analysis of pulmonary MIP-1α mRNA expression, Western blotting analysis of pulmonary NF- κB expression, RESULTS： Meconium - induced ALI was characterized by increased BAL cell count, increased expressions of pulmonary MIP - 1α mRNA and NF - κB protein [ （4.68 ± 1.40） × 10^9 cells/L vs （0.53 ± 0. 19） × 10^9 cells/L, 3.60 ± 0.75 vs 1.56 ± 0.33, 0.72 ± 0.31 vs 0.23 ± 0.12, respectively in control rats, all P 〈 0.01 ]. IT administration of rhSOD early in the ALl rat significantly decreased meconium - indueed BAL cell count [ （3.13 ± 0.77） × 10^9 cells/L vs （4.68 ± 1.40） × 10^9 cells/L in Mec/saline rats, P 〈 0.01 ], inhibited the expression of pulmonary, MIP- 1α mRNA （2,20 ± 0.39 vs 3,60 ± 0.75, in Mec/saline rats, P 〈 0.01 ） and NF- κB protein （0.44 ± 0.21 vs 0.72 ± 0.31 in Mee/saline rats, P 〈 0.05）. CONCLUSION： The early IT administration of rhSOD in ALl rat following meeoniunl aspiration protects lung from inflanunatory injury through inhibiting meconium - induced pulmonary MIP - let mRNA anti NF- κB protein expression.