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目的:观察盐酸戊乙奎醚(PHC)对脂多糖(LPS)性肺损伤(ALI)大鼠肺泡Ⅱ型上皮细胞(ATII)和肺组织细胞外信号调节激酶(ERK)活化的影响。方法:SD大鼠随机分为对照组、LPS组(静脉注射5 mg/kg LPS)和LPS+PHC高、中、低(3.0、1.0和0.3 mg/kg)3个剂量组,每组8只,测定肺湿重/干重(W/D)比值,考马斯亮蓝法测BALF蛋白含量,双缩脲法测血浆蛋白含量,并计算肺通透指数(LPI=BALF蛋白/血浆蛋白),透射电镜观察各组ATII超微结构,并进行PHC影响肺组织ERK表达的量效性分析;另取大鼠在注入生理盐水(NS)后即刻0 h(对照组)和注射LPS后2 h、4 h、6 h和12 h共5个时点,每时点6只,进行PHC影响肺组织ERK表达的时效性分析。蛋白免疫印迹法检测肺组织ERK的表达。结果:LPS组大鼠电镜下可见ATII板层小体排空明显而致空泡化,微绒毛脱落,微丝模糊、断裂、缩短,线粒体空泡变性,基膜不完整,而PHC显著减少ATII板层小体空泡化,减轻ATII损伤。LPS模型组大鼠肺W/D比值、LPI及肺组织磷酸化ERK表达显著高于对照组(均P<0.05),PHC高剂量组显著降低LPS诱导的大鼠肺W/D比值、LPI(均P<0.05),显著抑制LPS诱导的大鼠肺组织磷酸化ERK表达(P<0.05);PHC在LPS注射后6h时最能有效抑制ERK磷酸化。结论:PHC抑制LPS诱导的ALI大鼠肺组织通透性增加、ATII损伤和肺组织ERK活化,PHC对LPS诱导大鼠肺组织通透性增高和ATII损伤的拮抗作用可能与抑制ERK活化有关。
Objective: To observe the effect of penehyclidine hydrochloride (PHC) on the activation of alveolar type Ⅱ epithelial cells (ATII) and extracellular signal-regulated kinase (ERK) in lung tissue of lipopolysaccharide (LPS) -induced lung injury (ALI) Methods: SD rats were randomly divided into control group, LPS group (5 mg / kg LPS) and LPS + PHC high, medium and low doses (3.0, 1.0 and 0.3 mg / kg) (W / D) ratio, BALF protein content by Coomassie brilliant blue method, plasma protein content by biuret method, and pulmonary permeability index (LPI = BALF protein / plasma protein) The ultrastructures of ATII in each group were observed by electron microscope, and the dose-effect analysis of PHC on the expression of ERK in lung tissues was performed. The rats were sacrificed at 0 h immediately after NS injection (control group) and 2 h after LPS injection h, 6 h and 12 h at 5 time points, each time point 6, carry on the PHC affect the ERK expression in the lung tissue timeliness analysis. Western blot was used to detect the expression of ERK in lung tissue. Results: The LPS group showed obvious vacuolization, microvilli shedding, fuzzy microvilli, rupture, shortening of mitochondria, degeneration of mitochondria and incomplete basement membrane, while PHC significantly reduced ATII Lamellar body vacuolization, reduce ATII damage. LPS model rats lung W / D ratio, LPI and lung tissue phosphorylation ERK expression was significantly higher than the control group (all P <0.05), PHC high dose group significantly reduced LPS-induced lung W / D ratio, LPI ( P <0.05), and significantly inhibited the phosphorylation of ERK in LPS-induced lung tissue (P <0.05). PHC inhibited the ERK phosphorylation 6 h after LPS injection. CONCLUSION: PHC can inhibit the increase of lung tissue permeability, ATII injury and ERK activation in LPS-induced ALI rats. The antagonistic effect of PHC on LPS-induced lung tissue permeability and ATII injury may be related to the inhibition of ERK activation.