乌司他丁对鼠急性肺损伤的保护作用及相关因子的表达

目的 观察乌司他丁注射液对光气引起急性肺损伤时肿瘤坏死因子-α(TNF-α)表达的影响.方法 清洁级健康SD雄性大鼠64只,以随机数字表达法分为两大组共8个小组,即染毒组(乌司他丁干预组、光气染毒组、生理盐水对照组)和未染毒组(空气对照组、生理盐水空气对照组、乌司他丁空气对照组),每组各8只.空气对照组、生理盐水空气对照组、乌司他丁空气对照组吸入空气,光气染毒组、乌司他丁干预组和生理盐水对照组吸入同等浓度和相同时间的光气,并分别同等容积、不同种类和不同浓度的药物从尾静脉注射到大鼠体内并测量肿瘤坏死因子的变化情况,酶联免疫法测定肿瘤坏死因子的含量变化,荧光定量PCR测定TNF-αmRNA的表达情况.结果 实验大鼠64只全部进入结果分析:损伤组右下肺湿质量、干质量及湿/干质量比较空气对照组和乌司他丁空气对照组显著增加(P<0.01);乌司他丁治疗组和地塞米松治疗组右下肺湿质昔、干质量及湿/干比值较模型组明显降低(P<0.01)但仍明显高于对照组(P<0.01);对照组的肺组织大体观察可见表面光滑呈淡红色无充血水肿及梗死灶;光气染毒组和生理盐水组可见肺微血管出血和微血栓形成,肺间质和肺泡内有水肿液和炎症细胞的浸润,部分可见灶状肺不张,乌司他丁治疗组和地塞米松治疗组的病理学改变可见肺微血管充血出血微血栓形成及炎症细胞浸润,但比光气染毒组要稍轻;乌司他丁治疗组肿瘤坏死因子α的表达水平均高于空气对照组和乌司他丁空气对照组(P<0.01),但低于光气染毒组和生理盐水组(P<0.01).结论 乌司他丁可能通过抑制TNF-α的高表达来促进急性肺损伤的修复.

Protective effects of ulinastatin on phosgene-induced acute lung injury and the expression of tumor necrosis factor-alpha

Objective To observe the effects of ulinastatin on the expressions of tumor necrosis factor-α (TNF-α) in the lung tissues of rats with acute lung injmy induced by phosgene, and to explore the mechanism of ulinastafin in treating acute lung injury. Method Sixty-four clean grade healthy male SD rots were randomly divided(random number) into eight groups with eight in each group. Group A1 in which rats were exposed to air. Group A2 in which rots wereexposed to air and treated with saline. Group A3 in which rats were exposed to air and treated with dexamethasone. Group A4 in which mrs were exposed to air and treated with ulinastatin. Group B1 in which rots were exposed to phosgene without treatment. Group B2 in which rats were exposed to phosgene and treated with saline. Group B3 in which rats were exposed to phosgene and treated with dexamethasone. Group B4 in which rats were exposed to phosgene and treated with ulinastatin. The expressions of TNF-α in the lung tissues were measured by using immunohistocheistry. Lung tissues were observed grossly and under 200-fold light microscope to identify the positive expressions in kytoplasm. Results In group B1 and group B2, the wet weight, dry weight and wet/dry weight ratio og right lower lobe of lung were higher thai those in group A1 and group A4( P <0.01 ), and those in group B4 and group B3 were significantly lower than those in group B1(P<0.01 ), but still higher than those in group A1 and A4(P<0.01). The gross observation suggested that the surfaces of lung tissues in group A1and group A2 were slick and rose pink without congestion, dropsy or infarction; the surfaces of lung tissue in groups B1 and B2 appeared with congestion, dropsy and many petechia. The surfaces of lung tissue in groups B3 and B4 were similar to those in groups B1 and B2. Under the light microscope, the structure, of lungs in groups A1 and A2 were clear without congestion, effusion or inflammatory cell infiltration. In groups B1 and B2, the engorgement of lung capillary vessels, congestion and tiny thrombosis were found and there abundant edematous fluid and inflammatory cell infiltration in lung stroma and alveolus with focal pulmonary atelectasis in some lung tissue section. The tissues in groups B3 and B4 showed congestion, dropsy, tiny thrombosis and inflammatory cell infiltration, but these changes were slighter than those in groups B1 and B2. The expressions of TNF-α in groups B1, B2, B3, and B4 were significantly higher thanthose in groups A1 and A2( P < 0.01 ), but the expressions of TNF-α IN group B4 was lower than that in groups B1 and B2(P<0.01). Conclusions Ulinastatin could lessen the lung injury by reducing the expressions of pro-inflammatory cytokines such as TNF-α.