Chen T-H, Wang J-J
Division of Cardiovascular Surgery, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Transplant Proc. 2018 Nov;50(9):2860-2863. doi: 10.1016/j.transproceed.2018.03.052. Epub 2018 Mar 15.
Lung injury subsequent to pancreatic ischemia and reperfusion (PIR) due to shock, revascularization, and pancreas transplantation is a major clinical problem. In addition to proteases, massive production and release of reactive oxygen species (ROS) and induction of inflammatory cytokines have been implicated in remote lung injury. Niacin, also known as vitamin B, is both antioxidative and anti-inflammatory. In this study, we examined the protective effectiveness of niacin pretreatment against PIR-induced pancreatic and remote lung injury.
Male Sprague-Dawley rats were divided into a sham-operated group, a PIR group, and a PIR group pretreated with niacin; the niacin (300 mg/kg per day) was given on 4 consecutive days before the study. Pancreatic ischemia was established by occluding both the gastroduodenal and splenic arteries for 120 minutes, followed by 240 minutes of reperfusion. Lung injury was assessed by pulmonary barrier function via pulmonary filtration coefficient, K, using an isolated-perfused rat lung preparation. Alveolar protein leakage was assessed by protein concentration in the bronchoalveolar lavage fluid (PCBAL). Lung water content was assessed by both wet-weight/dry-weight ratio (W/D) and lung-weight/body-weight ratio (LW/BW). Lung inflammation was evaluated by the lavage differential neutrophil cell count and tissue tumor necrosis-alpha (TNF-α) level. Oxidative stress was assessed by tissue malondialdehyde (MDA) level. Serum lactate dehydrogenase (LDH) and amylase were examined for lung and pancreas injury. We also evaluated lung tissue SIRT1 mRNA expression.
Compared with the sham group, the PIR group had increased serum amylase and LDH, and impaired the pulmonary barrier dysfunction with marked increases in K, PCBAL, W/D, and LW/BW, and augumented oxidative stress and inflammation with elevated tissue MDA and TNF-α and lavage neutrophil count, which correlated with decreased SIRT1 mRNA expression. Conversely, niacin pretreatment reduced pancreatic and remote lung injury and attenuated pulmonary oxidative stress and inflammation, and also protected against PIR-induced pulmonary barrier dysfunction while restoring SIRT1 mRNA expression.
Niacin pretreatment reduced PIR-induced pancreatic and lung injury and protected against pulmonary barrier function impairment, which was associated with niacin's antioxidative and anti-inflammatory activity and its capacity to increase SIRT1 mRNA expression.
由于休克、血管再通和胰腺移植导致的胰腺缺血再灌注（PIR）后继发的肺损伤是一个主要的临床问题。除蛋白酶外，活性氧（ROS）的大量产生和释放以及炎性细胞因子的诱导也与远隔肺损伤有关。烟酸，也被称为维生素B，具有抗氧化和抗炎作用。在本研究中，我们检测了烟酸预处理对PIR诱导的胰腺和远隔肺损伤的保护效果。
将雄性Sprague-Dawley大鼠分为假手术组、PIR组和烟酸预处理的PIR组；在研究前连续4天给予烟酸（每天300mg/kg）。通过阻断胃十二指肠动脉和脾动脉120分钟建立胰腺缺血，随后再灌注240分钟。使用离体灌注大鼠肺标本，通过肺滤过系数K评估肺屏障功能来评价肺损伤。通过支气管肺泡灌洗液（PCBAL）中的蛋白质浓度评估肺泡蛋白渗漏。通过湿重/干重比（W/D）和肺重/体重比（LW/BW）评估肺含水量。通过灌洗中性粒细胞分类计数和组织肿瘤坏死因子-α（TNF-α）水平评估肺炎症。通过组织丙二醛（MDA）水平评估氧化应激。检测血清乳酸脱氢酶（LDH）和淀粉酶以评估肺和胰腺损伤。我们还评估了肺组织SIRT1 mRNA表达。
与假手术组相比，PIR组血清淀粉酶和LDH升高，肺屏障功能障碍，K、PCBAL、W/D和LW/BW显著增加，氧化应激和炎症增强，组织MDA、TNF-α升高，灌洗中性粒细胞计数增加，这与SIRT1 mRNA表达降低相关。相反，烟酸预处理减轻了胰腺和远隔肺损伤，减轻了肺氧化应激和炎症，还预防了PIR诱导的肺屏障功能障碍，同时恢复了SIRT1 mRNA表达。
烟酸预处理减轻了PIR诱导的胰腺和肺损伤，并预防了肺屏障功能损害，这与烟酸的抗氧化和抗炎活性及其增加SIRT1 mRNA表达的能力有关。
