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目的观察乌司他丁治疗后梗阻性黄疸大鼠肺的炎性浸润以及组织形态学改变,探讨乌司他丁对梗阻性黄疸大鼠肺的保护作用及其机制。方法通过胆总管结扎来建立梗阻性黄疸大鼠模型。乌司他丁治疗组术后每天给予乌司他丁10万U/kg的剂量腹腔注射给药,梗阻性黄疸对照组不进行治疗。分别在术后第1、3、7、14天取材,检测大鼠的肝功能、肺组织病理,计算干湿比及含水率,并测定肺通透性指标(伊文思蓝含量)、肺组织中髓过氧化物酶(MPO)活性以及丙二醛(MDA)含量,免疫组化测定肺组织标本TNF-α和IL-1β表达。结果乌司他丁治疗组血清胆红素含量、肺组织干湿比及含水率与梗阻性黄疸对照组相比,差异无统计学意义。而乌司他丁治疗组MPO、MDA及伊文思蓝含量较梗阻性黄疸对照组下降,差异有统计学意义(P<0.01)。乌司他丁治疗组与梗阻性黄疸对照组比较,肺间质水肿减轻,炎性细胞浸润和肺泡内红细胞渗出减少。乌司他丁治疗组第1天和第14天的TNF-α和IL-1β表达均低于同期梗阻性黄疸对照组。结论乌司他丁可抑制梗阻性黄疸大鼠致炎因子TNF-α和IL-1β在肺组织中的表达,降低中性粒细胞浸润并减少氧自由基的产生,改善肺泡毛细血管通透性,降低肺内炎症反应。
Objective To observe the inflammatory infiltration and histomorphological changes of pulmonary in obstructive jaundice rats after ulinastatin treatment and to investigate the protective effect and mechanism of ulinastatin on the lung of obstructive jaundice rats. Methods The model of obstructive jaundice was established by ligating the common bile duct. The ulinastatin group was treated with ulinastatin 100 000 U / kg intraperitoneally every day after operation, and the control group without obstructive jaundice was not treated. The rats were sacrificed on the 1st, 3rd, 7th and 14th day after operation to detect the liver function and pathology of the rats. The wet / dry ratio and the water content were calculated. The indexes of pulmonary permeability (Evans blue), lung tissue (MPO) activity and malondialdehyde (MDA) content in lung tissue were detected by immunohistochemical method. The expression of TNF-α and IL-1β in lung tissue were detected by immunohistochemistry. Results Ulinastatin treatment group serum bilirubin, lung wet and dry ratio and water content and obstructive jaundice control group, the difference was not statistically significant. The ulinastatin treatment group MPO, MDA and Evans blue content than obstructive jaundice control group decreased, the difference was statistically significant (P <0.01). Ulinastatin treatment group and obstructive jaundice in the control group, interstitial edema alleviated, inflammatory cell infiltration and alveolar erythrocyte effusion decreased. The expression of TNF-α and IL-1β in the ulinastatin group was lower than that in the obstructive jaundice control group on the first and the fourteenth day. Conclusion Ulinastatin can inhibit the expression of TNF-α and IL-1β in lung tissues of rats with obstructive jaundice, reduce the infiltration of neutrophils and reduce the production of oxygen free radicals and improve the permeability of alveolar capillary , Reduce inflammation in the lungs.