摘要
目的研究尿胰蛋白酶抑制剂(UTI)对脓毒症导致的大鼠模型肺组织损伤的保护作用。方法将清洁级雄性Wistar大鼠70只分为UTI组(30只)、模型组(30只)、假手术组(10只)。采用盲肠结扎穿刺(CLP)法制造脓毒症模型,分别在术后0、12 h给予UTI组静脉注射UTI 5×104U/kg,给予模型组和假手术组注射同等容量生理盐水,术后24 h测定动脉血气及乳酸(Lac);ELISA法检测血浆肿瘤坏死因子(TNF)-α、白介素(IL)-1β含量,HE染色观察肺组织病理改变,化学比色法测定肺组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,TUNEL法测定肺组织细胞凋亡,实时荧光定量PCR检测肺组织核转录因子-κB(NF-κB)mRNA的表达。结果与模型组相比较,UTI组24 h存活率高于模型组(χ2=1.669,P>0.05),肺组织病理改变减轻,急性肺损伤(ALI)评分显著降低(t=5.285,P<0.01);血浆TNF-α、IL-1β含量均显著降低(t=8.926,P<0.01;t=10.105,P<0.01);肺组织SOD活性显著升高(t=5.440,P<0.01),MDA的含量显著降低(t=6.632,P<0.01),细胞凋亡指数明显降低(t=7.539,P<0.01),NF-κB mRNA表达降低(t=3.276,P<0.01)。结论 UTI可以通过调控NF-κB信号转导通路的活性,减轻炎症级联放大效应,降低氧化应激水平,减少肺组织细胞凋亡,进而减轻脓毒症导致的肺损伤。
Objective To investigate the protective effect of urinary trypsin inhibitor（UTI） on lungs of septic rats,so as to provide theoretical basis for clinical treatment.Methods The sepsis model was established by cecum ligation and puncture（CLP）,and the UTI group received an intravenous administration of 5×104 U/kg at 0 h and 12 h after the operation,while the model group and sham operation group were given the same amount of saline.24 h after the operation,rats were killed to collect the lungs and plasma specimen.The arterial blood gas and lactic acid were measured.The expression of TNF-α and IL-1β in the plasma were detected by ELLSA.The pathological changes of the lung tissue were demonstrated by HE staining.Chemical colorimetry method was used to determine the levels of SOD and MDA in the lung tissue.The apoptotic cells were detected by TUNEL method.The NF-κB mRNA expression was examined by real-time fluorescence quantitative PCR.Results The survival rate of rats in UTI group was higher than that in model group（χ2=1.669,P0.05）.HE staining showed the pulmonary pathological changes were attenuated in the UTI group compared with the model group,and the lung injury scores were decreased（t=5.285,P0.01）.The levels of TNF-α and IL-1β in the plasma were lower in the UTI group than that in model group（t=8.926,P0.01;t=10.105,P0.01）.Compared with the model group,the activity of SOD was higher in UTI group（t=5.440,P0.01）,and the level of MDA was lower（t=6.632,P0.01）.The number of apoptosis cells in the lung tissue was significantly decreased in UTI than that in the model group（t=7.539,P0.01）.The NF-κB mRNA expression was down regulated in the UTI group compared with the model group（t=3.276,P0.01）.Conclusion UTI can play a protective role in acute lung injury resulting from sepsis.NF-κB signal pathway might participate in restraining the inflammatory responses,inhibiting the oxidation stress,and reducing the apoptosis in lung tissue.
出处
《山东大学学报（医学版）》
CAS
北大核心
2012年第9期15-20,共6页
Journal of Shandong University:Health Sciences
基金
山东省科技攻关计划(2006GG2202008)
