硫氧还蛋白-1在急性坏死性胰腺炎大鼠肺组织中的表达及褪黑素干预的影响

Effects of melatonin on Trx-1 expression in the lungs of rats with acute necrotizing pancreatitis

目的:探讨内源性硫氧还蛋白-1(Trx-1)在急性坏死性胰腺炎(ANP)大鼠模型肺组织中的表达;观察褪黑素对ANP胰和肺脏的保护作用和对肺组织Trx-1表达的影响.方法:将72只SD大鼠随机分成对照组(C组,n=24)、急性胰腺炎组(A组,n=24)、褪黑素前干预组(M组,n=24).A组用6%的左旋精氨酸(L-Arginine,L-Arg)腹腔内注射,每次25mL/kg体质量,共3次,注射间隔1h,诱导ANP模型,在首次注射L-Arg前30min腹腔注射生理盐水20mL/kg体质量1次;C组同法注射相当于A组各次注射用量的等容积生理盐水;M组在诱导胰腺炎前30min腹腔内注射0.25%褪黑素(20mL/kg体质量)干预.在注射完L-Arg后的6、12、24h三个时点分批处死大鼠,应用免疫组织化学技术检测各组ANP肺组织Trx-1的表达,并观察各组对应各时点胰腺、肺组织病理学和肺免疫组织化学的改变;抽取动脉血测定Trx-1和淀粉酶.结果:A组大鼠胰腺和肺组织病理损伤在6、12、24h时点比C组明显加重(均P<0.01);M组胰腺和肺组织病理损伤在6、12、24h时点较A组明显减轻(P<0.01或0.05).A组、M组肺组织表达Trx-1量在6、12、24h时点较C组显著升高(均P<0.01).在24h,A组血清淀粉酶较C组显著升高(4598U/L±2274U/Lvs2033U/L±863U/L,P<0.01);M组较A组低(3990U/L±1146U/Lvs4598U/L±2274U/L,P<0.05).A组大鼠血清Trx-1含量在6、12h时点显著降低,24h时点显著升高,呈前低后高趋势;与A组比较,M组血清Trx-1在6、12h时点显著升高,24h时点显著降低,量的峰值前移.结论:Trx-1在ANP肺损伤组织中的过度表达与急性胰腺炎相关性肺损伤关系密切.褪黑素影响Trx-1表达,并可能在一定程度上减轻ANP的胰、肺组织损伤.

AIM： To investigate the expression of thioredoxin-1 （Trx-1） in the lungs of rats with L-arginine （L-Arg）-induced acute necrotizing pancreatitis （ANP） and assess the effects of melatonin on Trx-1 expression. METHODS： Seventy-two male Sprague-Dawley rats were randomly divided into three groups：normal control group, model control group and melatonin intervention group. The ANP model group was intraperitoneally injected three times with 6% L-Arg at a dose of 25 mL/kg body weight at an interval of 1 h to induce ANP. The normal control group was intraperitoneally in-jected with equal volumes of normal saline. The melatonin intervention group was injected intra-peritoneally with 0.25% melatonin at a dose of 20 mL/kg body weight half an hour before ANP induction. Rats were executed at 6, 12 and 24 hours after last L-Arg injection. The expression of Trx-1 in the lungs was detected by immuno-histochemistry. The pathological changes in the pancreas and lungs were analyzed and scored according to Kusser’s and Lei’s criteria, respec-tively. The contents of serum Trx-1 and amylase were measured. RESULTS： At 6, 12 and 24 hours after last L-Arg injection, the pathological changes in the pan-creas and lungs in the model control group were more severe than those in the normal control group （all P 0.01）. However, the pathological changes in the pancreas and lungs in the mela-tonin intervention group were milder than those in the model control group （P 0.01 or 0.05）. At 24 hours, the content of serum amylase in the model control group was significantly higher than that in the normal control group （4 598 U/L ± 2 274 U/L vs 2 033 U/L ± 863 U/L, P 0.01）. In contrast, the content of serum amylase in the melatonin intervention group was lower than that in the model control group （3 990 U/L ± 1 146 U/L vs 4 598 U/L ± 2 274 U/L, P 0.05）. Compared to the normal control group, serum Trx-1 contents in the model control group significantly decreased at 6 and 12 hours but significantly increased at 24 hours. The contents of serum Trx-1 in melatonin intervention group at 6 and 12 hours were significantly higher than those in the model control group. CONCLUSION： Lung injury is closely related to pancreatic injury in ANP. The expression of Trx-1 in the lungs of rats with ANP increasessignificantly. Overexpression of Trx-1 in the lungs is closely associated with the development of ANP and acute pancreatitis-associated lung injury. Melatonin can, to a certain extent, alter the expression of Trx-1 and reduce pancreatic and pulmonary injury in ANP in rats.