海狗油对内毒素致大鼠急性肺损伤的保护作用及其机制研究

Protective effect of seal oil on LPS-induced acute lung injury in rats

目的:探讨海狗油软胶囊对内毒素的主要成份脂多糖(lipopolysaccharide,LPS)诱导大鼠形成急性肺损伤(acute lung injury,ALI)的保护作用及其作用机制。方法:SD大鼠分为6组:空白对照组、模型对照组、阳性对照组、海狗油高剂量组(H)、中剂量组(M)和低剂量组(L),除空白对照组外,其余大鼠尾静脉注射(iv)LPS 6 mg·kg-1造成急性肺损伤模型,造模前1周,分别灌胃(ig)海狗油1,0.5和0.25 g·kg-1,qd,连续7 d,末次给药1 h后LPS造模,阳性对照组造模同时ivω-3鱼油脂肪乳注射液1 g·kg-1,造模24 h后大鼠眼静脉丛取血并用二氧化碳窒息处死,测定各组大鼠血清肿瘤坏死因子(tumor necrosis factor,TNF-α)、白细胞介素1(interleukin-1,IL-1)和白细胞介素6(interleukin-6,IL-6),测肺脏湿重和干重比值(W/D),观察各组大鼠肺组织的病理改变等。结果:造模后大鼠体温升高,海狗油各剂量组与模型组相比,体温显著降低(P<0.01);核转录调节因子(NF-κB)和致炎细胞因子TNF-α,IL-1和IL-6都有不同程度地表达下调;W/D值显著降低(P<0.05)。各组大部分肺泡结构尚好,肺组织损伤程度低,明显好于模型组。结论:海狗油软胶囊对大鼠急性肺损伤具有保护作用,其作用机制可能与抑制NF-κB信号通路、抑制炎症细胞因子的表达有关。

Objective： To observe the preventive effect of seal oil soft capsules on lipopolysaccharide（ LPS）-induced acute lung injury（ ALI）. Methods： SD rats were randomly divided into six groups： blank control group,model group,positive control group,high（ H）,middle（ M） and low（ L） dose seal oil group. Except the blank control group,the rest rats were treated by iv injection of LPS of 6 mg·kg^-1 through tail to set up ALI model after ig administration of seal oil at the dose of 1,0. 5,and 0. 25 g·kg^-1 for a week,while the rats in the positive group were intravenously given ω-3 fish oil fat emulsion injection at 1 g·kg^-1 on the day of ALI modelling. After 24 h blood samples were taken through the eye venous plexus and the rats were executed by carbon dioxide asphyxiation. Serum levels of tumor necrosis factor（ TNF-α）,interleukin-1（ IL-1）,and interleukin-6（ IL-6） and the ratio of wet weight to dry weight（ W / D） of lungs were determined. The pathologic changes of the lung tissues were observed. Results： The rats had acute body temperature increases after injection of LPS. The rats in the seal oil groups of different doses all had significantly lower body temperature than the LPS model group（ P〈0. 01）.The serum levels of cytokines TNF-α,IL-1 and IL-6 were significantly decreased for the three dose groups of seal oilsoft capsules compared with the LPS model group. The W / D ratios in all the seal oil groups were decreased significantly than the LPS model group（ P〈0. 05）. The alveolar structure of the rats in the high,medium and low dose seal oil groups remained good with low degree of lung injury,which was significantly better than the model group. Conclusion： Seal oil soft capsules have protective effect on acute lung injury. The mechanism may be inhibiting the expressions of inflammatory factors NF-κB and cytokines.