糖皮质激素治疗结核性胸腔积液的实验研究

Effects of glucocorticoids on tuberculous pleural effusion： experiment with rats

目的探讨糖皮质激素治疗结核性胸腔积液的价值。方法用标准人型结核分枝杆菌菌株H。Rv0．03mg注入Wistar大鼠胸腔内，建立结核性胸腔积液的动物模型。将90只模型大鼠随机分成2组，每组45只。（1）激素组：注菌后24h在大鼠右大腿内侧肌内注射曲安奈德注射液0．3mg／只。（2）对照组：注菌后不作任何处理。注药后8、24、32、48h和3、5、7、10、15d每组各处死5只大鼠，解剖胸腔，记录胸腔积液量，观察胸腔、胸膜和肺组织大体和镜下病理变化，检测胸腔积液中白细胞数及分类和蛋白质、葡萄糖、乳酸脱氢酶（LDH）、可溶性细胞间黏附分子1（sICAM一1）、转化生长因子B1（TGF—B1）、1干扰素（IFN．1）水平。结果激素组大鼠在用药后8—48h的各个时点胸腔积液量均明显少于对照组（P〈0．05，P〈0．01）；用药后3d胸腔积液即完全消失。激素组大鼠胸腔积液中白细胞计数在用药后24—48h的各时点、中性粒细胞比例在用药后8—48h的各时点均明显低于对照组（均P〈0．01）；蛋白质含量在用药后32和48h明显高于对照组（均P〈0．01）；LDH在24h内明显低于对照组（P〈0．01）；sICAM一1和TGF—B1在8h高于而48h低于对照组（均P〈0．01）；IFN·1在8~48h的各时点均明显高于对照组（均P〈0．01）；IFN一∥TGF—B1比值随时问而升高，8—48h的各时点均明显高于对照组（均P〈0．01）。病理学检查显示激素组平均胸膜厚度明显低于对照组，胸膜下及肺间质血管充血及间质水肿程度也比对照组轻。结论早期使用激素治疗结核性胸腔积液可降低胸膜腔的炎症反应，加速积液的吸收，减轻胸膜增厚。

Objective To explore the effects of systemic glucocorticoid treatment on tuberculous pleural effusion. Methods Ninety Wistar rats were intrapleurally injected with 0. 03 mg of standard human Mycobacterium tuberculosis to establish models of tuberculous pleural effusions and then were randomly divided into 2 equal groups both without anti-tuberculosis treatment, glucocorticoids group （GG） undergoing intramuscular injection of 0. 3 mg triamcinolone acetonide in the right thigh 24 h after intrapleural injection, and control group （CG） received nothing as control. 8, 24, 32, and 48 hours, and 3, 5, 7, 10, and 15 days after intramuscular injection 5 rats from each group were killed. The thorax was opened, the amount of pleural effusion （PE） was recorded, and the pleural cavity, histopathology of pleura and lung parenchyma were examined. The white blood cell （ WBC ） count and differential leukocyte count, and levels of total protein （TP）, glucose （GLU）, and lactic dehydrogenase （LDH） in the PE were determined. Bioassays were used to detect the PE levels of soluble intercellular adhesion molecule-1 （ slCAM-1 ）, transforming growth factor β1 （ TGF-β1 ） , and interferon γ （IFN-γ）. Results The PE volumes of GG 8 -48 h after the intramuscular injection were significantly lower than those of CG （ P 〈 0. 05, P 〈 0. 01 ）, and PE completely disappeared on day 3. The WBC in PE 24 -48 h after and the percentages of neutrophils 8 -48 h after the intramuscular injection of GG were all significant lower than those of CG （ all P 〈 0. 01 ）. The TP levels 32 and 48 h after the intramuscular injection of GG were both significantly higher than those of CG （ both P 〈 0.01 ）. The LDH level of GG within 24 h after the i11tramuscular injection was significantly lower than that of CG （P〈 0. 01 ）. Both the sICAM--γ and TGF-β1 levels of GG were higher 8 h after the intramuscular injection, but lower 48 h after the intramuscular injection than those of CG （ both P 〈 0. 01 ）. The IFN-γ levels 8 - 48 h after the intramuscular injection of GG were all higher than those of CC （ all P 〈 0. 01 ）. The IFN-γ/TGF-β1 ratios at different time points of GG were all higher than those of CG, and there were significant differences in those 8 -48 h after the intramuscular injection between these 2 groups （all P 〈 0.01）. Pathologically, the mean thickness of pleura in GG was significantly less than that in CG. Congestion and edema in subpleura and pulmonary interstitium were less in GG than in CG. Conclusion Early use of glucocorticoids helps reduce the inflammatory response in pleural cavity in tuberculous pleurisy accelerate the absorption of pleural effusion and decrease the thickness of pleura.