Objective

To observe the differentiation of macrophages in lung tissue and alveolar lavage fluid of mice with severe pulmonary infection and the changes after intervention with ceftriaxone and ulinastatin, and to explore the pathogenesis of severe pulmonary infection under immunosuppressive state and the intervention effect of two drugs.

Methods

40 male Balb/c mice are randomly divided into normal group, model group, ulinastatin group, and ceftriaxone group with 10 mice in each group. Mice models of acute lung injury with immunodeficiency are established by methylprednisolone and endotoxin, and then treated with ulinastatin and ceftriaxone. Respiratory frequencies of mice in each group are measured at 3 h and 6 h after drug use through trachea, and then the mice are anaesthetized with uratan and killed 6 h after drug use. The number of alveolar macrophages and neutrophils in alveolar lavage fluid is collected and detected, and the pathological changes are observed. The positive expression of CD163 in lung tissue is detected by IHC (immunohistochemistry), and real-time quantitative PCR (Polymerase Chain Reaction) is used to detect the expression of Ml and M2 markers in bronchoalveolar lavage fluid (BALF).

Result

Compared with the normal group, the mice in the model group breathed shallowly and quickly, occasionally nodded breathing, respiratory distress, and respiratory rate increased. Compared with the model group, the mice in the ulinastatin group and ceftriaxone group breathed slowly, occasionally have shortness of breath, smooth breathing, and slow breathing rate, and the mice in ulinastatin group breathe more smoothly. The number of macrophages and neutrophils in BALF of model group is higher than that of normal group. The number of macrophages and neutrophils in ulinastatin group and ceftriaxone group is lower than that of model group and the difference is statistically significant, and the number of macrophages and neutrophils in ulinastatin group is relatively less than that in model group.

Conclusion

In the early stage of severe pulmonary infection under immunosuppressive state, the organism is in the CARS (Compensatory Anti-inflammatory Response Syndrome) stage; M1 macrophages had immune paralysis and M2 macrophages are abnormally activated. Compared with ceftriaxone, ulinastatin can alleviate lung injury more effectively and protect the lung of mice with acute lung injury. The protective mechanism of ulinastatin on lung of mice infected with immunocompromised endotoxin may be through inhibiting M1 macrophages and regulating non-specific immune function.

中文翻译：

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不同治疗对慢性阻塞性肺疾病和反复肺部感染巨噬细胞分化的影响[J].

客观的

观察重症肺部感染小鼠肺组织和肺泡灌洗液中巨噬细胞的分化情况及头孢曲松和乌司他丁干预后的变化，探讨免疫抑制状态下重症肺部感染的发病机制及两种药物的干预效果。

方法

40只雄性Balb/c小鼠随机分为正常组、模型组、乌司他丁组和头孢曲松组，每组10只。用甲泼尼龙和内毒素建立免疫缺陷急性肺损伤小鼠模型，然后用乌司他丁和头孢曲松治疗。用药后3、6小时通过气管测量各组小鼠呼吸频率，然后用乌拉坦麻醉小鼠，用药后6小时处死。收集并检测肺泡灌洗液中肺泡巨噬细胞和中性粒细胞的数量，并观察其病理变化。IHC（免疫组化）检测肺组织CD163阳性表达，

结果

与正常组相比，模型组小鼠呼吸浅而快，偶有点头呼吸，呼吸窘迫，呼吸频率增加。与模型组相比，乌司他丁组和头孢曲松组小鼠呼吸缓慢，偶有呼吸急促、呼吸顺畅、呼吸频率减慢，乌司他丁组小鼠呼吸更顺畅。模型组BALF中巨噬细胞和中性粒细胞数量高于正常组。乌司他丁组和头孢曲松组巨噬细胞和中性粒细胞数量低于模型组，差异有统计学意义，乌司他丁组巨噬细胞和中性粒细胞数量相对少于模型组。

结论

在免疫抑制状态下的重症肺部感染早期，机体处于CARS（代偿性抗炎反应综合征）阶段；M1巨噬细胞免疫麻痹，M2巨噬细胞异常激活。与头孢曲松相比，乌司他丁能更有效地减轻肺损伤，保护急性肺损伤小鼠的肺。乌司他丁对免疫功能低下内毒素感染小鼠肺的保护机制可能是通过抑制M1巨噬细胞和调节非特异性免疫功能。