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目的探讨乌司他丁对急性肺损伤(acute lung injury,ALI)大鼠肺组织糖皮质激素受体α(glucocorticoid receptor alpha,GRα)、糖皮质激素受体β(glucocorticoid receptor beta,GRβ)表达的影响。方法将72只成年雄性SD大鼠随机分为3组:空白对照组(n=24)、脂多糖组(LPS组,n=24)和脂多糖加乌司他丁组(LU组,n=24),各组又分为4、8、12、24 h 4个不同时间点,每个时间点各6只。LPS组腹腔注射LPS(5 mg/kg);LU组腹腔注射LPS(5 mg/kg)后,即刻腹腔注射乌司他丁(10万U/kg)。各组补足生理盐水至腹腔注射总体积为1 ml。光镜下观察肺组织HE染色病理学变化;同时测定大鼠肺湿干重比(W/D);采用蛋白印迹分析技术检测GRα、GRβ的表达。以灰度值表示其相对表达水平。结果病理检查证实大鼠ALI造模成功。在各时间点3组大鼠肺组织GRα、GRβ的表达:LPS组大鼠肺组织GRα表达水平均低于对照组(P均<0.01),GRβ均高于对照组(P均<0.01);LU组GRα表达水平均高于LPS组(P均<0.05),但仍低于对照组(P均<0.05),GRβ与GRα相反。LPS组内各时间点肺组织GRα、GRβ表达水平比较差异有统计学意义(P<0.05,P<0.01),GRα于8 h降到最低,然后递升;GRβ于8 h达到最高,然后递降。LU组内各时间点肺组织GRα、GRβ表达水平比较差异有统计学意义(P<0.05,P<0.01),随时间延长GRα表达递降,GRβ递增并于8 h达到最高,然后递降。结论 ALI大鼠GRα和GRβ在肺组织中的表达较正常肺组织有所改变,乌司他丁对ALI大鼠有保护作用,可能与其可调控GRα和GRβ的表达有关。
Objective To investigate the effects of ulinastatin on the expression of GRα, GRβ in lung tissue of acute lung injury (ALI) rats. influences. Methods Seventy-two male Sprague-Dawley rats were randomly divided into 3 groups: control group (n = 24), lipopolysaccharide group (n = 24) and lipopolysaccharide plus ulinastatin group 24), each group is divided into 4,8,12,24 h 4 different time points, each time point 6 each. LPS group was injected intraperitoneally with LPS (5 mg / kg). LU group was given intraperitoneal injection of ulinastatin (10 000 U / kg) immediately after intraperitoneal injection of LPS (5 mg / kg). Each group make up the normal saline to the total volume of intraperitoneal injection of 1 ml. The pathological changes of lung tissue were observed under light microscope. The wet / dry weight ratio (W / D) of lungs was also measured. The expression of GRα and GRβ was detected by Western blotting. The relative expression levels are expressed as gray values. Results The pathological examination confirmed the success of rat model of ALI. The expression of GRα and GRβ in the lungs of the three groups at each time point: the expression of GRα in the lung tissue of the LPS group was lower than that of the control group (all P <0.01), while the GRβ was higher than that of the control group (all P <0.01). The expression of GRα in LU group was higher than that in LPS group (all P <0.05), but still lower than that in control group (all P <0.05). The levels of GRα and GRβ in lung tissue at each time point in LPS group were significantly different (P <0.05, P <0.01). GRα decreased to the lowest level at 8 h and then increased. GRβ reached the peak at 8 h and then decreased. The expression of GRα and GRβ in lung tissues at each time point had statistical significance (P <0.05, P <0.01). The expression of GRα decreased gradually with the increase of time and reached the peak at 8 h and then decreased. Conclusions The expressions of GRα and GRβ in lung tissue of ALI rats are different from those in normal lung tissues. Ulinastatin has a protective effect on ALI rats, which may be related to the regulation of GRα and GRβ expression.