姜黄素和地塞米松对大鼠移植肺缺血再灌注损伤的保护作用

Protective effects of curcumin or dexamethasone on ischemia-reperfusion injury of rat lung grafts

目的研究姜黄素(CUR)和地塞米松(DXM)对大鼠移植肺缺血再灌注损伤的干预作用。方法实验分四组进行,CUR组肺移植前3 h供、受者腹腔注射CUR溶液;DXM组肺移植前30 min受者腹腔注射DXM溶液;载体组肺移植前3 h供、受者腹腔注射CUR的溶剂二甲基亚砜;假手术组不进行肺移植。每组分别于恢复血液再灌注2 h和24 h各处死大鼠6只,采取颈动脉(CA)血和左肺静脉(LPV,移植侧)血,测定血氧合指数(PP_2/FiO_2)以及血清中丙二醛(MDA)、总抗氧化能力(TAOC)、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)的含量;同时行肺组织病理学观察,测定肺湿重与干重比(W/D),以及肺组织中髓过氧化物酶活性(MPO)、MDA、TAOC、TNF-α、IL-6的含量。结果再灌注2 h及24 h,CUR组及DXM组LPV血的PO_2/FiO_2明显高于载体组(P<0.01)。CUR组与DXM组再灌注2 h和24 h的肺水肿病理评分和总分明显低于载体组(P<0.017),CUR组与DXM组再灌注24 h的W/D明显低于载体组(P<0.01)。再灌注2 h和24 h,CUR组与DXM组肺组织中MPO含量明显低于载体组(P<0.05,P<0.01)。再灌注2 h时,CUR组和DXM组血清和组织中MDA含量明显低于载体组(P<0.05),再灌注24 h时,CUR组血清MDA含量和DXM组组织中MDA含量明显低于载体组(P<0.05)。再灌注2 h和24 h,CUR组肺组织和血清中TAOC含量明显高于载体组(P<0.01,P<0.05),而DXM组仅再灌注2 h的肺组织和再灌注24 h的血清中TAOC含量高于载体组(P<0.01)。再灌注2 h和24 h,CUR组和DXM组肺组织中TNF-α和IL-6含量低于载体组。结论CUR和DXM对大鼠移植肺缺血再灌注损伤具有保护作用,其机制可能与二者具有抗氧化和抗炎作用有关。

Objective To investigate the curative effects of curcumin （CUR） or dexamethasone （DXM） on ischemia-reperfusion injury （IRI） of rat lung grafts. Methods Male SD rats were randomly divided 4 groups： CUR group （CUR was administered intraperitoneally to both donors and recipients at 3 h prior to operation）; DXM group （DXM was administered intraperitoneally at 30 rain prior to operation） ; vehicle group （Animals were injected with the DMSO to both donors and recipients at 3 h prior to operation） ; sham group （Time-matched control animals underwent the same surgery, except that no graft was implanted）. Six animals were sacrificed at different reperfusion periods of 2 h and 24 h, respectively. Oxygenation indexes （PO2/FiO2）, lung injury scores, wet/dry ratio （W/D） and myeloperoxidase （MPO） activity in the transplanted lung were measured. Malondialdehyde （MDA）, total anti-oxidative capacity （TAOC）, tumor necrosis factor （TNF）-α and interleukin （IL）-6 in the transplanted lung and serum were determined. Results The levels of LPV PO2/FiO2 were significantly higher in the CUR and DXM groups than in the vehicle groups both 2 and 24 h after reperfusion, respectively （P〈0. 01）. The extent of pulmonary edema and the total scores in CUR and DXM groups were significantly decreased at 2 and 24 h after reperfusion as compared with those in vehicle group,respectively （P〈0. 017）. Pretreatment with CUR or DXM significantly decreased W/D of grafts at 24 h after reperfusion, as compared to vehicles （P〈0. 01）. Pretreatment with DXM and CUR significantly inhibited the increase of MDA levels in tissue and serum at 2 h （P〈0. 05）. After 24 h reperfu- sion, MDA levels in serum could be decreased by CUR （P〈0. 05）, while MDA levels in tissue could be decreased by DXM （P〈0. 05）. CUR could inhibited the decrease of TAOC levels in serum and tissue at 2 and 24 h after reperfusion, respectively （P〈0. 05,P〈0. 01） ; TAOC levels in tissues at 2 h after reperfusion and those in serum at 24 h after reperfusion were significantly higher in the DXM group than in the vehicle group, respectively （P〈0. 05）. Levels of TNF-α and IL-6 in grafts of CUR and DXM groups were decreased as compared with those in vehicle group at 2 and 24 h after reperfusion, respectively. Conclusion Administration of CUR or DXM attenuated ischemia-reperfusion injury of lung grafts by inhibiting oxidation and inflammation.