慢性阻塞性肺疾病急性加重期痰热证与痰湿证模型生物学指标的比较研究

A comparative study of biological indicators of phlegm-heat syndrome （痰热证） and phlegm-dampness syndrome （痰湿证） model with acute exacerbation of chronic obstructive pulmonary disease

目的从炎症反应、激素水平、肺组织病理损伤、肺功能方面评价慢性阻塞性肺疾病急性加重期（AECOPD）痰热证与痰湿证动物模型的异同。方法将56只Wistar大鼠按随机数字表法均分为正常组、AECOPD组、AECOPD痰热证组和AECOPD痰湿证组。观察大鼠外周血白细胞计数（WBC）、中性粒细胞比例，血清游离三碘甲状腺原氨酸（FT1）、游离甲状腺素（FT4）、肾上腺素（E）、去甲肾上腺素（NE）、皮质醇（c0R）、c-反应蛋白（CRP）、肿瘤坏死因子-α（TNF—α）、白细胞介素-8（IL-8）和支气管肺泡灌洗液（BALF）中TNF-α、IL-8及细胞间黏附分子-1（ICAM-1）水平，测定大鼠肺功能，观察肺组织病理改变。结果①痰湿证组外周血WBC和中性粒细胞比例〉痰热证组〉AECOPD组〉正常组，两两比较差异明显。3个模型组血清及BALF中炎症因子水平明显高于正常组，其中痰湿证组血清IL-8[（4．13±1．28）μg／L]、CRP[（3．07±0．69）μg／L3明显高于痰热证组[（1．75±0．53）μg／L，（1．98±0．42）μg／L，均P〈0．01]。③AECOPD组和痰热证组FT3[（9．44±3．17）μmol／L，（9．95±3．68）μmol／L]较正常组[（4．53±2．80）pmol／L]显著升高，痰湿证组FT3[（2．13±1．31）μmol／L31]下降（P〈0．05或P〈0．01）。痰湿证组血清FT3[（2．23±0．71）pmol／L]、E[（87．27±29．32）nmol／L]、NE[（71．69±21．24）nmol／L]均显著低于正常组[FT4（4．64±1．49）pmol／L，E（143．94±32．90）nmol／L，NE（100．32±27．73）nmol／L，P〈0．05或P〈0．01]，AECOPD组各指标与正常组无明显差异，痰热证组各指标显著高于AECOPD组；痰湿证组c0R〉痰热证组〉AECOPD组≈正常组。⑧3个模型组气管周围炎性细胞浸润，纤毛倒伏、脱落，肺泡囊扩大；痰热证组、痰湿证组大鼠病理改变较AECOPD组明显，而两组间气管周围炎性细胞浸润程度相似。④3个模型组呼吸峰流速（PEF）、潮气量（Vt）及分钟通气量（MV）较正常组明显降低，但呼吸频率（f）和吸气阻力（Rin）水平显著增高，这些指标以痰湿证组变化显著；而痰热证组与AECOPD组间上述指标无明显差异。结论AECOPD痰热证和痰湿证模型动物的局部及全身炎症反应、肺组织病理损伤较单纯AECOPD模型更明显，且痰湿证模型在全身炎症反应、甲状腺和肾上腺髓质指标水平及肺功能减退方面均较痰热证模型更严重。

Objective To compare phlegm-heat syndrome （痰热证） with phlegm-dampness syndrome （痰湿证） of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） in regard to inflammatory response, hormone level, lung pathological examination and lung function. Methods Fifty-six Wistar rats were randomly divided into four groups, including normal control group, AECOPD group, phlegm-heat syndrome of AECOPD group （PHs group）, phlegm-dampness syndrome of AECOPD group （PDs group）. The level of white blood cell （WBC） count, neutrophil ratio, free triiodothyronine （FT3）, free thyroxine （FT4）, epinephrine （E）, norepinephrine （NE）, cortisol （COR）, C-reactive protein （CRP）, tumor necrosis factor-α （TNF-α）, interleukin-8 （IL-8） in blood, and TNF-α, IL-8, intercellular adhesion molecule-1 （ICAM-1） in broncho-alveolar lavage fluid （BALF） were determined with radioimmunology. Lung function was tested by whole-body plethysmography. Results ①The count of WBC and neutrophil ratio in PDs group were higher than in PHs group, AECOPD group and normal group, there was significant difference in multiple comparison. The levels of inflammatory mediators in serum and BALF in three model groups were evidently higher than in normal group, and IL-8 [（4.13 ± 1.28） μg/L] and CRP [（3. 07±0. 69） μg/L] in serum in PDs group were higher than those in PHs group [（1.75± 0. 53） μg/L, （1.98 ± 0. 42） μg/L, both P〈 0. 013. ②FT3 level in blood in both AECOPD group and PHs group [（9.44±3.17） pmol/L, （9.95 ± 3.68） pmol/L] was significantly higher than that in normal control group [（4. 53±2. 80） pmol/L3, FT3 in PDs group [（2.13±1. 31） pmol/L] was evidently lower than that in normal group （P〈0.05 or P〈0.01）. The level of FT4[（2.23±0. 71） pmol/L], E [（87. 275±29.32） nmol/L3 and NE [（71. 695=21.24） nmol/L] in PDs group were all obviously lower than those in normal group [FT4： （4. 64± 1.49） pmol/L, E： （143. 945± 32.90） nmol/L, NE： （100. 32±27.73） nmol/L, P（0.05 or P〈 0. 01 3. There was no significant difference in the above three parameters between AECOPD group and normal group. Each parameter in PHs group was markedly higher than that in AECOPD group. The content of COR in PDs group was higher than in PHs group, in which COR was higher than in AECOPD group, which was equal to that in normal group. ③The pathological changes in lung included inflammatory cell infiltration, exfoliation of cilia, dilatation of alveolar spaces of lung tissue in AECOPD group, which were more significant in PHs group and PD group. Inflammatory cells infiltration around the bronchi, thickening of interalveolar spaces, and vasodilatation were more pronounced in PHs group and PDs group than in AECOPD group. Inflammatory cell infiltration around the bronchi were about the same between PHs and PDs groups. ④The levels of peak expiratory velocity （PEV）, tidal volume （VT）, minute ventilation （MV） were significantly lower in AECOPD group, PHs group and PDs group than in normal control group, but the levels of frequency （f） and inspiratory resistance （Rin） were evidently higher. Compared with AECOPD group, the levels of PEV, VT, MV were significantly decreased, the level of respiratory f and Rin evidently increased in PDs group. Compared with PHs group, the levels of PEV, VT, MV significantly decreased in PDs group, while the level of f and Rin evidently increased. There was no significant difference in the above five parameters between AECOPD group and PHs group. Conclusion The changes in local and systemic inflammatory response, lung histopathological injury in PHs group and PDs group were more evident than changes in AECOPD group. The changes in systemic inflammatory response, decrease in functional indicators of thyroid and adrenal medulla, and decline in lung function were more marked in PDs group than in PHs group.