盐酸戊乙奎醚减轻脂多糖诱导的大鼠肺损伤

Penehyclidine hydrochloride attenuates LPS-induced acute lung injury in rats

目的探讨盐酸戊乙奎醚(PHCD)对脓毒症休克大鼠肺脏的保护作用。方法 36只健康SD大鼠随机分为正常对照组、脂多糖(LPS)处理组和PHCD处理组。利用大鼠腹腔注射LPS(5 mg/kg)制备休克模型,然后通过尾静脉注射PHCD(1.0 mg/kg)治疗,注射6 h后进行大鼠血气分析,处死大鼠后检测每组大鼠肺的干湿质量比(W/D),ELISA检测支气管肺泡灌洗液(BALF)中白细胞介素8(IL-8)、IL-6及肿瘤坏死因子α(TNF-α)的水平,HE染色观察肺组织炎症反应,实时定量PCR检测肺组织诱导型一氧化氮合酶(i NOS)的mRNA水平,Western blot法检测肺组织i NOS蛋白水平。结果与对照组相比,LPS处理组肺W/D和血乳酸(LAC)显著升高,pH值和动脉氧分压(PaO_2)显著下降,BALF中TNF-α、IL-8和IL-6水平均明显增加,肺组织中i NOS表达明显上调;LPS处理组大鼠肺部明显水肿、充血、白细胞渗出增加。经过PHCD治疗的大鼠,肺W/D和LAC降低,pH值和PaO_2上升,BALF中TNF-α、IL-8、IL-6含量均有明显降低,肺组织中i NOS水平明显下降,肺部炎症反应减轻。结论 PHCD可抑制LPS诱发的肺部炎症、减轻肺损伤。

Objective To study the protective effect of penehyclidine hydrochloride（ PHCD） against acute lung injury induced by lipopolysaccharide（ LPS） in rats. Methods 36 Sprague Dawley（ SD） rats were randomly divided into control group,LPS-induced shock group（ LPS group）,and PHCD treated group（ PHCD group）. Rat shock model was prepared by intraperitoneal injection of LPS（ 5 mg/kg）. The rats of PHCD group were treated with PHCD（ 1. 0 mg/kg） by caudal vein injection. Rat blood gas analysis was performed 6 hours after the injection. Lung wet/dry mass ratio（ W/D） was detected after the rats were sacrificed. The levels of tumor necrosis factor α（ TNF-α）,interleukin 8（ IL-8）,and IL-6 in bronchoalveolar lavage fluid（ BALF） were tested by ELISA. The lung tissue inflammation was observed by HE staining. The expression of inducible nitric oxide synthase（ i NOS） was detected by real-time quantitative PCR and Western blot analysis.Results Compared with the control group,lung W/D and blood lactate acid（ LAC） increased significantly in the LPS group,while the blood pH and the arterial oxygen partial pressure（ PaO_2） decreased markedly. The levels of TNF-α,IL-8 and IL-6 significantly increased in lung BALF of the LPS-induced rats,and the expression of i NOS increased significantly. HE staining showed that LPS treatment caused pulmonary edema,congestion and inflammatory cell infiltration. After PHCD treatment,lung W/D and LAC were reduced; the pH and PaO_2 were elevated compared with LPS-induced rats; the levels of TNF-α,IL-8 and IL-6 in BALF were evidently down-regulated; the expression of i NOS decreased obviously. HE staining showed that the lung inflammation was attenuated by PHCD treatment. Conclusion PHCD attenuates lung injury by inhibiting LPS-induced lung inflammation.