目的探讨注射用红花黄色素对油酸致大鼠急性肺损伤的作用及其机制。方法Wistar大鼠随机分成对照组、油酸组(模型组)、油酸+山莨菪碱10mg/kg组、油酸+红花黄色素(8、16、32mg/kg)组,每组12只,各组在iv油酸0.18g/kg前给予药物干预。油酸损伤4h后,测定大鼠动脉血血氧分压、左肺含水系数和肺组织髓过氧化物酶(MPO)活性;RT—PCR法检测肺组织肿瘤坏死因子-a(TNF—a)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)mRNA表达水平;免疫组织化学法观察肺组织NF-kBp65活化细胞数;Western blotting法检测p38MAPK蛋白磷酸化水平。结果红花黄色素组大鼠动脉血血氧分压值均高于模型组,肺组织含水系数和MPO活性均低于模型组;同时各炎症因子mRNA表达水平,NF—kBp65阳性细胞数和p38MAPK蛋白磷酸化水平也均低于模型组。结论红花黄色素可缓解急性肺损伤所致肺水肿,提高动脉血氧分压,减少肺部炎性细胞浸润,其作用机制可能与抑制p38MAPK磷酸化及NF-kB活化,下调TNF-a、IL-β等炎症因子的表达有关。
Objective To investigate the effects of safflor yellow (SY) injection on acute lung injury (ALI) rats induced by oleic acid (OA) and its potential mechanism. Methods Wistar rats were randomly divided into six groups, including control group, OA group, OA+10 mg/kg anisodamine group, OA+8 mg/kg SY group, OA+16 mg/kg SY group, and OA+32 mg/kg SY group. Normal saline or anisodamine or SY were pretreated before 0.18 g/kg OA iv injection. The arterial partial pressure of oxygen, the pul- monary water content index, and MPO activity in lung tissue were determined; The mRNA level of TNF- a, IL-1β, IL-6, ICAM-1, and VCAM-1 were measured by RT-PCR; And NF-kB p65 protein in nucleus observed by immunohistochemical technology, while the level of p38 MAPK protein phosphorylation in lung tissue was analyzed by Western blotting. Results The arterial partial pressure of oxygen in all SY groups was higher than that in OA group, while the pulmonary water content index and MPO activity were lower than those in OA group, as well as the mRNA level of the above inflammatory cytokines and the NF- kB p65 in nucleus and level of p38 MAPK phosphorylation. Conclusion SY could alleviate the lung tissue edema, increase the arterial partial pressure of oxygen, and depress MPO activity in ALI rat induced by OA. The SY mechanism of attenuating the acute lung injury may be associated with inhibiting the p38 phosphorylation and NF-kB activation and reducing inflammatory factors expression.