辛伐他汀对急性肺损伤及囊性纤维化跨膜传导调节体表达的影响

目的:探讨辛伐他汀对急性肺损伤大鼠囊性纤维化跨膜传导调节体(CFTR氯离子通道)的影响及其对减轻急性肺损伤的作用。方法:40只雄性SD大鼠随机分为空白组、模型组、辛伐他汀低剂量组(20 mg/kg)、辛伐他汀中剂量组(40 mg/kg)、辛伐他汀高剂量组(80 mg/kg);气道内滴注脂多糖(10 mg/kg)制备急性肺损伤模型。进行肺湿/干重比、肺泡灌洗液蛋白检测,HE染色观察肺组织的病理变化;实时荧光定量PCR检测肺组织匀浆CFTR mRNA表达。结果:结果显示,模型组的肺湿干重比,肺泡灌洗液蛋白较空白组高(P0.05),病理示肺泡膈增厚,大量炎性细胞浸润,肺泡腔内可见红细胞及血肿,提示模型复制成功。辛伐他汀低剂量组的肺湿/干重比、肺泡灌洗液蛋白与模型组相比无明显差异,病理可见肺损伤较重,与模型组相比无改善;CFTR mRNA表达与模型组相比稍高但无明显差异(P0.05)。辛伐他汀中高剂量组中肺湿/干重比、肺泡灌洗液蛋白与模型组相比有所降低,肺组织CFTRmRNA表达较模型组明显增加(P0.05),但中高剂量组之间无明显差异(P0.05);病理可见肺泡膈增厚,极少见炎性细胞浸润及透明膜,肺泡腔内未见明显出血和水肿,肺损伤程度较模型组减轻。结论:中高剂量的辛伐他汀(40 mg/kg)对急性肺损伤有一定保护作用,并上调CFTR的表达。

Role of Simvastatin in Rats with Acute Lung Injury and Expression of Cystic Fibrosis Membrane Conductance Regulator

Objective:To investigate the effect of simvastatin on the expression of cystic fibrosis transmembrane conduction regulating body (CFTR chloride ion channels) in rats with acute lung injury, and its role in alleviating the acute lung injury.Methods:40 male SD rats were randomly divided into blank group, ALI model group, low dose simvastatin group (20 mg/kg), middle dose simvastatin group (40 mg/kg) and high dose simvastatin group (80 mg/kg); We established a rat model of acute lung injury by intratracheal instillation of lipopolysaccharide (LPS) with a dose of 10 mg/kg. The wet-dry (W/D) ratio of the lung, total protien in the bronchoalveolar lavage fluid (BALF) were examined, HE statining were used to observe the pathological changes in lung tissue of rats; and the expression of CFTR mRNA in lung tissues was determined with quantitative RT-PCR (Q-PCR).Results:The results showed that the W/D of lung and total protein of BALF in ALI model group were higher than those in blank group (P<0.05); In pathological examination of lung tissue, ALI model group was characterized by a wider alveolar septum, a large number of inflammatory cell infiltration, alveolar wall swelling and destruction, a large number of edema and hemorrhage in lung parenchyma. Those results showed that the model of acute lung injury was established. Compared with ALI model group, the W/D of lung, total protein of BALF had no significantly difference in low dose simvastatin group (P>0.05); pathological examination of lung tissue injury did not show significant difference. Moreover, CFTR mRNA expression in low dose simvastatin group was slightly higher than ALI model group (P>0.05). In the middle and high dose simvastatin groups, the W/D of lung and total protein of BALF were lower than those in ALI model group (P<0.05), while CFTR mRNA expression was remarkably higher than that in ALI model group (P<0.05); pathological examination revealed that the lung tissue injury in middle and high dose simvastatin groups were milder than that in ALI model group. In pathological examination, The middle and high dose simvastatin groups showed alveolar septum thickening. However, It is hardly to see inflammatory cell infiltration and hyaline membranes in lung parenchyma, alveolar edema and hemorrhage can not be seen in those groups as well. Furthermore, middle dose simvastatin group has no difference fromhigh dose simvastatin group in CFTR mRNAexpression (P>0.05).Conclusion:Middle and high dose (>40 mg/kg) simvastatin can ameliorate acute lung injury by lipopolysaccharide (LPS), this may relate with up-regulating CFTRmRNA expression.