槲皮素对脓毒症急性肺损伤大鼠肿瘤坏死因子-α／白细胞介素-1β的影响

The effects of quercetin on levels of tumor necrosis factor-α and interleukin-1β in rats with acute lung injury associated with sepsis

【摘要】目的观察槲皮素对脓毒症相关急性肺损伤（ALI）大鼠肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）的影响，以及槲皮素对脓毒症时的肺保护作用。方法选用健康雄性Wistar大鼠35只，按随机数字表法分为对照组（5只）、模型组（10只）、槲皮素高剂量组（75mg／kg，10只）和槲皮素低剂量组（50mg／kg，10只）。腹腔注射脂多糖（LPS）10mg／kg2ml建立脓毒症ALI大鼠模型；对照组给予等量生理盐水。治疗组于制模前30min腹腔注射槲皮素。各组于制模后6、12、24h取血，采用酶联免疫吸附法（ELISA）检测血清中TNF-α、IL-1β含量；于制模后24h腹腔注射水合氯醛麻醉并处死大鼠，取肺组织行苏木素-伊红（HE）染色观察组织病理学改变，取肺叶测定肺组织湿／干重比值（W／D比值）。结果与对照组比较，模型组制模后6h血清TNF-α（ng／L）、IL-1β（ng／L）含量即明显升高（TNF-α：73．00±0．28比28．48±0．26，IL-1β：46．30±0．21比28．38±1．07，均P〈0．01），肺W／D比值明显升高（5．710±0．025比3．860±0．034，P〈O．01）；与模型组比较，槲皮素低、高剂量组制模后6hTNF-α、IL-1β含量即明显下降（TNF-α：55．52±0．31、57．76±0．27，IL-1β：39．47±9．65、41．83±0．16，均P〈0．05），肺组织病理改变明显好转，肺w／D比值明显下降（4．810±0．036、4．900±0．029，均P〈O．05），两治疗组间炎症介质比较差异无统计学意义；高剂量组肺组织病理损伤改善程度明显优于低剂量组。结论槲皮素可下调大鼠血清TNF-α、IL-1β含量，对脓毒症ALI大鼠的肺组织起保护作用。

Objective To investigate the effects of quereetin on the levels of tumor necrosis faetor-α （TNF-α） and interleukin-1β （IL-1β） in rats with acute lung injury （ALI） associated with sepsis and its proteetive effect on such lungs. Methods Thirty-five healthy Wistar rats were divided by random numeric table method into four groups： control group （5 eases）, model group（10 eases）, Quereetin high level treated group （75 mg/kg, 10 eases） and quereetin low level treated group （50 mg/kg, 10 eases）. The ALI rat model was established by intra-peritoneal （i. p. ） injection of lipopolysaeeharide （LPS, 10 mg/kg）, which was dissolved in normal saline up to 2 ml, the rat in control group was administered with normal saline 2 ml by i.p. injection, Quereetin groups received their respective quereetin dosages by i.p. injection 30 minutes before the modeling; 6, 12, 24 hours after the modeling, the levels of TNF-α and IL-1β were measured by enzyme-linked immunoadsorbent assay （ELISA） in serum. All the rats were anesthetized by intra-peritoneal injection of 10% Chloral Hydrate and were sacrificed, the lung was seetioned and stained with hematoxylin-eosin （HE） to make pathological examinations, and at the same time, the wet and dry weight ratios （W/D ratio） of the lung were ealeulated and eompared. Results Compared with control group, model group showed a significant inerease in the levels of TNF-α （ng/L） and IL-1β （ng/L） from 6 hours after the modeling （TNF-α： 73.00±0. 28 vs. 28.48±0.26, IL-1β 46.30±0.21 vs. 28.38±1.07, all P〈0.01）, the wet and dry ratios （W/D ratio） of the lung were also significantly increased （5. 710±0. 025 vs. 3. 860±0. 034, P〈0.01） ; in the two quereetin treatment groups, the levels of TNF-α and IL-1β were signifieantly lower than those in model group from 6 hours after the modeling （Quereetin low level treated group：TNF-α： 55.52 ± 0. 31, IL-1β： 39.47±9.65; Quereetin high level treated group ：TNF-α： 57.76±0. 27, IL-1β： 41. 83±0.16, all P〈0. 05）, the pathological changes in lung tissue were milder than those in ALI group, and W/D ratio of the lung were signifieantly deereased （Quereetin low level treated group 4. 810± 0. 036, Quereetin high level treated group 4. 900±0. 029, both P〈0.05）; there were no significant differences between the two Quereetin treated groups in the levels of inflammatory mediators ; compared with quereetin low level treated group, the pathological changes in lung tissue in Quereetin high level treated group showed obviously milder in degree. Conclusion Quereetin ean down-regulate the levels of TNF-α and IL-1β and has a protective effect on lung tissues in rats with septic ALI.