姜黄素对小鼠单肺通气诱导急性肺损伤的影响

摘要

Objective To investigate the effect of curcumin (Cur)on acute lung injury (ALI) induced by one-lung ventilation (OLV)in mice.Methods Sixty C57BL/6J mice were randomly alloca-ted into six groups (n =10):two-lung ventilation group (TLV group),OLV group,OLV+Cur pre-treated with 50 mg/kg group (Cur50 group),100 mg/kg group (Cur100 group),1 50 mg/kggroup (Cur1 50 group)and200 mg/kg group (Cur200 group).Peak and averaged airway pressure (Ppeak and Paw)of mice in each group were recorded.Mice were euthanized and the end of experiment,and left lung tissue was excised.Wet lung weight to dry lung weight (W/D)and total lung water content (TLW)were tested.Pathological changes of lung tissue were observed under light microscope,and changes of ultrastructure of lung tissue were observed by transmission electron microscope.Index of quantitative evaluation for alveolar damage (IQA)and lung injury scores were tested under light mi-croscope.The expression of c-Jun N-terminal kinase (JNK)mRNA and phosphorylated JNK (p-JNK)protein were detected respectively by reverse transcription-polymerase chain reaction (RT-PCR)and Western Blot.Apoptosis index (AI)of lung tissue was determined by terminal dexynucle-otidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL)method.Results There was no statistical significance at Ppeak and Paw of rats in each group.Compared to TLV group,the expres-sion of JNK mRNA and p-JNK protein were all significantly increased (P <0.05)in OLV group,and W/D,TLW,IQA,lung injury scores and AI were all notably higher (P <0.05);morphological and ultrastructural injuries in lung tissue were notably occured in OLV group.Compared to OLV group,the expression levels of JNK mRNA and p-JNK protein were decreasingly lower (P <0.05 )in the groups of Cur100,Cur1 50 and Cur200,W/D,TLW,IQA,lung injury scores and AI were also de-creased (P <0.05);morphological and ultrastructural injuries in lung tissue were gradually alleviated in the groups of Cur100,Cur1 50 and Cur200.However,there was no statistical significance in the in-dexes mentioned above between Cur50 group and OLV group.Conclusion Cur at doses of 100 to 200 mg/kg has protective effects on lung against OLV injury in mice,which may be related to inhibition of pneumocyte apoptosis induced by JNK.%目的：评价姜黄素(Cur)对小鼠单肺通气(OLV)诱导急性肺损伤(ALI)的影响。方法 C57BL/6J 小鼠60只,按照随机数字表法分为六组(n =10)：双肺通气组(TLV 组)、OLV 组、OLV+Cur 50 mg/kg 组(Cur50组)、OLV+Cur 100 mg/kg 组(Cur100组)、OLV+Cur 150 mg/kg组(Cur150组)和 OLV+Cur 200 mg/kg 组(Cur200组)。记录六组小鼠 OLV、TLV 时气道压峰值(Ppeak)和平均气道压(Paw)。实验结束后留取左肺,测定肺湿干/重比(W/D)和总肺水含量(TLW),光镜下观察肺组织形态学改变和进行肺组织损伤定量评估(IQA)及计算肺组织损伤评分,电镜观察肺组织超微结构改变,逆转录-聚合酶链反应(RT-PCR)和蛋白免疫印迹法(Western blot)分别检测 c-Jun 氨基末端激酶(JNK)mRNA 及磷酸化 JNK(p-JNK)蛋白表达水平,原位末端细胞凋亡检测(TUNEL)法检测肺组织细胞凋亡指数(AI)。结果与 TLV 时比较,OLV 时 OLV 组、Cur50组、Cur100组、Cur150组和 Cur200组小鼠 Ppeak 和 Paw 明显升高(P <0.05),OLV 组 W/D、TLW、IQA、AI 和肺组织伤损评分、JNK mRNA 及 p-JNK 蛋白表达水平明显升高(P <0.05)。与 OLV 组和 Cur50组比较,Cur100组、Cur150组和 Cur200组 W/D、TLW、IQA、AI 和肺组织伤损评分、JNK mRNA 及 p-JNK 蛋白表达水平明显下降(P <0.05)。与 Cur100组比较,Cur150组和 Cur200组 W/D、TLW、IQA、AI 和肺组织伤损评分、JNK mRNA 及 p-JNK 蛋白表达水平明显下降(P <0.05)。与Cur150组比较,Cur200组 W/D、TLW、IQA、AI 和肺组织伤损评分、JNK mRNA 及 p-JNK 蛋白表达水平明显下降(P <0.05)。结论姜黄素100~200 mg/kg 对 OLV 后肺损伤发生的小鼠肺脏具有较好的保护作用,其机制可能与其抑制 JNK 诱导的细胞凋亡有关。