烟碱对大鼠移植肺NF-κB表达和细胞因子的影响

Effect of intraperitoneal injection of nicotine on NF-κB and cytokines expression in rat lung transplantation

目的评价外源性烟碱对大鼠移植肺损伤以及NF-κB表达和细胞因子的影响。方法雄性Wistar大鼠40只,随机分为3组,假手术组(S组;8只);肺移植组(C组;16只,供体、受体各8只);肺移植+烟碱处理组(N组;16只,供体、受体各8只)。S组只进行开胸等操作不进行肺移植;N组于肺移植术后15min时腹腔注射烟碱2 mg/kg。肺移植术后2 h取移植肺组织,进行肺组织病理损伤(LIS)评分,测定肺组织湿/干重比(W/D),采用免疫组化染色测定肺组织NF-κB表达,ELISA法测定血浆TNF-α、IL-1β和IL-6的浓度。结果 C组NF-κB的表达明显高于N组和S组,S组NF-κB的表达最低。与C组比较N组和S组血浆IL-6、IL-1β和TNF-α浓度降低。与C组比较,N组和S组W/D和LIS评分降低;但N组仍比S组W/D和LIS评分高。结论外源性烟碱可能通过激活胆碱能抗炎通路减少NF-κB的表达及随后TNF-α、IL-1β和IL-6的合成,减轻大鼠移植肺损伤。

Objective To investigate the effect and possible mechanism of intraperitoneal injection of nico-tine on lung injury induced by lung transplantation in rat. Methods 40 male Wistar rats were randomly divided into three groups：the control group （ the group C） ventilated with 50% oxygen for 120 min after lung transplantation, the sham group （the group S）, and the nicotine group （the group N） received intraperitoneal injection of nicotine （2 mg/kg） after lung transplantation. The equal amount of normal saline was given to rats in the group C. All rats were sacrificed 120 min after lung transplantation by exsanguination. The wet to dry weight ratio （ W/D） of lung tissue was measured. Lung tissue histological score （ lung injury score, LIS） was performed. TNF-α, IL-1βand IL-6 in serum were measured by enzyme-linked immunosorbent assay （ ELISA） . The protein expression of NF-κB in lung tissue was detected by immunohistochemical staining. Results The levels of serum IL-6, IL-1βand TNF-αin the group N and the group S were significantly lower than those in the group C （ P〈0. 05 ） . The expression of NF-κB in the lung-transplanted rats was significantly higher than that in the sham operation group （ P〈0. 05 ） , but it was significantly lower in the group N than in the group C. The value of W/D and LIS was the lowest in the group S, followed by the group N and the group C （ P〈0. 05 ） . Conclusion Intraperitoneal injection of nicotine can alleviate inflammatory response of transplanted lung. The mechanism is more likely that the nicotine actives cholinergic anti-inflammatory pathway to suppress the expression of NF-κB and proinflammatory factor.