脓毒症大鼠肺组织中尿激酶型纤溶酶原激活剂受体的表达及其与肺损伤程度的相关性研究

目的探讨脓毒症大鼠肺组织中尿激酶型纤溶酶原激活剂受体（uPAR）表达变化及其与肺损伤的关系。 方法将48只雄性成年大鼠分为假手术组及脓毒症组，每组各24只大鼠。采用盲肠结扎穿孔术建立脓毒症损伤模型，假手术组大鼠只行开腹手术、不行结扎及穿孔，各组分别在术后6、12、24 h各取8只大鼠分批处死后收集肺泡灌洗液并留取肺脏。观察所有大鼠各时间点肺组织病理变化，测定肺组织干湿重比及肺泡灌洗液中蛋白变化，并采用免疫组织化学染色测定uPAR表达情况。 结果光镜下可见，假手术组大鼠肺组织肺泡结构完整，术后24 h只有少量炎症细胞浸润；脓毒症组大鼠肺泡腔内大量炎症细胞浸润，肺泡结构破坏，并以术后24 h最明显。两组大鼠各时间点肺组织干湿重比、肺泡灌洗液蛋白水平及uPAR表达比较，差异均有统计学意义（F = 32.000、97.770、72.780，P均< 0.001）。与假手术组相比，脓毒症组大鼠6、12、24 h肺组织干湿重比[（0.75 ± 0.03）vs.（0.78 ± 0.03）；（0.77 ± 0.04）vs.（0.83 ± 0.05）；（0.78 ± 0.04）vs.（0.89 ± 0.05）]、肺泡灌洗液蛋白水平[（79 ± 22）mg/L vs.（110 ± 40）mg/L；（79 ± 23）mg/L vs.（168 ± 36）mg/L；（94 ± 24）mg/L vs.（199 ± 56）mg/L]及uPAR表达[（2.2 ± 1.3）分vs.（4.6 ± 1.9）分；（2.3 ± 0.9）分vs.（6.4 ± 1.8）分；（2.4 ± 0.9）分vs.（7.0 ± 1.8）分]均明显升高（P均< 0.05）；且脓毒症组大鼠12、24 h亚组肺组织干湿重比、肺泡灌洗液蛋白水平均显著高于6 h亚组，而uPAR表达仅24 h亚组显著高于6 h亚组（P均< 0.05）。同时，肺组织中uPAR表达与肺组织干湿重比、肺泡灌洗液蛋白浓度均呈正相关（r = 0.618，P< 0.001；r = 0.652，P< 0.001）。 结论与假手术组相比，uPAR在脓毒症大鼠肺组织中表达明显增加，并且与肺损伤程度呈正相关。

Expression of urokinase plasminogen activator receptor in lung tissue of septic rats and its correlation with lung injury

ObjectiveTo investigate the expression of urokinase plasminogen activator receptor (uPAR) in lung tissue of septic rats and its relationship with lung injury. MethodsForty-eight male adult rats were randomly divided into a sham operation group and a sepsis group, with 24 rats in each group. The sepsis-induced injury was induced by cecal ligation and puncture (CLP) in the sepsis group, and rats in the sham operation group only underwent laparotomy, without ligation and perforation. Eight rats in each group were sacrificed at 6, 12, and 24 h after surgery respectively to collect lung tissue and bronchoalveolar lavage fluid. The pathological changes of lung tissue were observed; the wet/dry weight ratio of lung tissue and protein content of bronchoalveolar lavage fluid were detected. The uPAR expression was determined by immunohistochemical staining. ResultsUnder optical microscope, rats in the sham operation group had intact alveolar structure of lung tissue, and only a few inflammatory cells infiltrated at 24 h after laparotomy. However, a considerable number of inflammatory cells infiltrated into the alveolar cavity, and the alveolar structure was destroyed in the sepsis group, which was most obvious at 24 h after CLP. The wet/dry weight ratio, protein content of bronchoalveolar lavage fluid and uPAR expression were significantly different at each time point between the two groups (F = 32.000, 97.770, 72.780; all P < 0.001). Compared with the sham operation group, the wet/dry weight ratio [(0.75 ± 0.03) vs. (0.78 ± 0.03), (0.77 ± 0.04) vs. (0.83 ± 0.05), (0.78 ± 0.04) vs. (0.89 ± 0.05)], protein content of bronchoalveolar lavage fluid [(79 ± 22) mg/L vs. (110 ± 40) mg/L, (79 ± 23) mg/L vs. (168 ± 36) mg/L, (94 ± 24) mg/L vs. (199 ± 56) mg/L] and uPAR expression [(2.2 ± 1.3) vs. (4.6 ± 1.9), (2.3 ± 0.9) vs. (6.4 ± 1.8), (2.4 ± 0.9) vs. (7.0 ± 1.8)] in the sepsis group increased markedly at 6, 12, and 24 h after CLP (all P < 0.05). In the sepsis group, the wet/dry weight ratio and protein content of bronchoalveolar lavage fluid at 12 and 24 h were much higher than those at 6 h, and the uPAR expression at 24 h was much higher than that at 6 h (all P < 0.05). Meanwhile, the uPAR expression was positively correlated with the wet/dry weight ratio and protein content of bronchoalveolar lavage fluid (r = 0.618, P < 0.001; r = 0.652, P < 0.001). ConclusionCompared with the sham operation group, the uPAR expression increases significantly in the lung tissue of septic rats and is positively correlated with the degree of lung injury.