糖皮质激素治疗二氧化氮致大鼠急性肺水肿实验初步研究

目的 探讨糖皮质激素对二氧化碳(NO2)所致大鼠急性肺水肿的治疗效果.方法 将SD大鼠随机分为空白对照组、染毒组及大、中、小剂量糖皮质激素治疗组,每组6只.空白对照组予净空气平衡30 min,染毒组及大、中、小剂量糖皮质激素治疗组在NO2染毒后分别给予生理盐水2.5 mg/kg和地塞米松6.0、3.0、1.0 mg/kg.测定大鼠肺湿干重比(W/D),用ELISA法测定血浆心房利尿钠肽(ANP)含量、全血超氧化物歧化酶(SOD)活力及血浆中白细胞介素-6(IL-6)、IL-10、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)的含量.结果 与空白对照组比较,大、中、小剂量激素治疗组及染毒组大鼠肺W/D明显升高,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组大鼠肺W/D明显降低,差异有统计学意义(P<0.05).与空白对照组比较,大、中、小剂量激素治疗组及染毒组大鼠全血中SOD活力明显降低,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组全血中SOD活力无明显改变,差异无统计学意义(P>0.05).与空白对照组比较,染毒组大鼠血浆中ANP含量明显升高,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组大鼠血浆中ANP含量明显降低,差异有统计学意义(P<0.05).与染毒组[(68.55±27.84)pg/ml]比较,大、中、小剂量激素治疗组大鼠血浆中TNFα含量[分别为(27.04±8.19)、(40.10±9.09)、(39.76±9.60)pg/ml]明显降低,差异有统计学意义(P<0.05).与染毒组[(29.29±9.31)pg/ml]比较,大、中剂量激素治疗组大鼠血浆中IL-6含量[分别为(15.97±6.18)、(19.69±5.52)pg/ml]降低,差异有统计学意义(P<0.05).与染毒组[(44.38±9.19)pg/ml]比较,大、中、小剂量激素治疗组大鼠血浆中IL-10含量[(23.24±5.14)、(27.78±8.17)、(33.29±10.42)pg/ml]降低,差异有统计学意义(P<0.05).与染毒组[(30.83±6.82)pg/ml]比较,大、中剂量激素治疗组大鼠血浆中IFN-γ含量[分别为(7.21±4.55)、(19.23±4.35)pg/ml]降低,差异有统计学意义(P<0.05).结论 大、中、小剂量糖皮质激素均具有改善肺泡壁和毛细血管的通透性及非特异性的抗炎作用,对肺水肿有明显的治疗作用,在降低炎性因子方面,以大、中剂量激素治疗组效果更为明显.

Preliminary experimental research on glucocorticoid for treatment of nitrogen dioxide induced acute pulmonary edema in rats

Objective To investigate the therapeutic effect of glucocorticoids on the acute pulmonary edema in rats induced by nitrogen dioxide(NO2). Methods Thirty SD female rats were randomly equally divided into 5 groups: normal control group, NO2 exposed group, high-,middle-and low-dose of glucocorticoids treated group (6 rats per group) . 6 rats in the normal control group were exposed to room air for 30 min, and the other rats to NO2. 18 rats in the glucocorticoids group were treated with different doses of dexamethasone (6.0, 3.0, 1.0 mg/kg), while the rats in the NO2 poisoning group were treated with normal saline (2.5 mg/kg).The lung wet/dry (W/D) weight ratio was calculated, and plasma atrial natriuretic peptide (ANP) levels, superoxide dismutase (SOD) activity from whole blood, plasma interleukin 6 (IL-6), interleukin 10 ( IL- 10), tumor necrosis factor- α (TNF-α) and Interferon-γ (IFN-γ)were detected by enzyme-linked immunosorbent assay (ELISA). Results The lung W/D ratios were increased significantly in glucocorticoids treated group and NO2-exposed group compared with normal control group (P<0.05), while they were significantly reduced in glucocorticoids treated group as compared with NO2-exposed group (P<0.05). SOD activity in whole blood in glucocorticoids treated group and NO2-exposed group was significantly lower than that of normal control group (P<0.05), while it was no significant difference between that of glucocorticoids treated group and NO2 -exposed group (P>0.05). Plasma ANP was significantly increased in NO2-exposed group compared with normal control group (P<0.05), while it was significantly decreased in glucocorticoids treated group compared with NO2 -exposed group(P>0.05 ). Plasma TNF-α of high-,middle- and low- dose of glucocorticoids treated group[(27.04±8.19), (40.10±9.09), (39.76±9.60) pg/ml] was decreased significantly as compared with NO2-exposed group (68.55 ±27.84 pg/ml) (P<0.05). Plasma IL-6 in high-and middle-dose of glucocorticoids treated group [( 15.97±6.18 )、 ( 19.69±5.52 ) pg/ml] was significantly decreased as compared to NO2-exposed group[(29.29±9.31 ) pg/ml] (P<0.05). Plasma IL- 10 in high-,middle-and low- dose of glucocorticoids treated group[(23.24±5.14), (27.78 ±8.17), (33.29±10.42) pg/ml] was significantly reduced compared with NO2-exposed group [(44.38 ±9.19) pg/ml] (P<0.05). Plasma IFN-γ in high-and middle-dose of glucocorticoids treated group [(7.21±4.55 ), ( 19.23±4.35 ) pg/ml] was reduced compared with NO2-exposed group[(30.83±6.82 ) pg/ml](P<0.05 ). Conclusion High-,middle-,low -dose glucocorticoids all can improve the permeability of alveolar wall and capillary, and have nonspecific anti-inflammatory effects. The therapeutic effects on pulmonary edema re significant. High and middle dose of glucocorticoids treated group are more useful for decreased inflammatory factors.