【目的】 观察大黄素调节Janus激酶2（JAK2）/转录激活因子3（STAT3）信号通路对卒中相关性肺炎（SAP）大鼠肺损伤的 影响。【方法】 采用改良线栓法结合气管注射铜绿假单胞菌法建立SAP大鼠模型。将造模成功的大鼠随机分为模型组，大黄 素低、高剂量组，大黄素高剂量+香豆霉素（JAK2激活剂）组，每组12只，另选出12只SD大鼠设为假手术组。干预后，测定 动脉血气指标二氧化碳分压（PaCO2）、氧分压（PaO2），测定肺湿/干质量比，进行支气管肺泡灌洗液（BALF）中炎性细胞计数， 采用苏木素-伊红（HE）染色法观察肺组织病理形态并进行病理损伤评分，采用酶联免疫吸附分析（ELISA）检测肺组织中髓过 氧化物酶（MPO）活性，BALF和血清中白细胞介素6（IL-6）、环氧化酶2（COX-2）水平，采用Western Blot法检测肺组织JAK2/ STAT3 通路关键蛋白表达。【结果】 与假手术组比较，模型组大鼠肺组织发生明显病理损伤，PaCO2值，肺湿/干质量比， BALF 中白细胞数及嗜酸性粒细胞数，病理损伤评分，肺组织 MPO 活性水平，BALF 和血清 IL-6、COX-2 水平，肺组织 p-JAK2/JAK2及p-STAT3/STAT3比值均显著升高，PaO2值显著降低，差异均有统计学意义（P < 0.05）；与模型组比较，大黄 素低、高剂量组大鼠肺组织病理损伤均减轻，PaCO2值，肺湿/干质量比，BALF中白细胞数及嗜酸性粒细胞数，病理损伤评 分，肺组织 MPO活性水平，BALF和血清 IL-6、COX-2水平，肺组织 p-JAK2/JAK2及 p-STAT3/STAT3比值均降低，PaO2值 升高，差异均有统计学意义（P < 0.05），且大黄素高剂量组作用效果更强；香豆霉素可减弱大黄素对模型大鼠上述各指标的 改善作用。【结论】 大黄素可通过抑制JAK2/STAT3信号通路活化下调SAP大鼠炎症水平，进而减轻肺损伤，改善肺功能。

Objective To observe the effect of emodin on lung injury in rats with stroke associated pneumonia （SAP）through regulating Janus kinase 2（JAK2）/signal transducer and activators of transcription 3（STAT3） signaling pathway. Methods The SAP rat model was established by modified thread embolization method combined with intratracheal injection of Pseudomonas aeruginosa method. The successfully modeled rats were randomly divided into model group， emodin low-and high-dose groups and emodin high-dose + coumermycin （JAK2 activator）group，with 12 rats in each group，and another 12 SD rats were selected as the sham-operated group. After the intervention， the partial pressure of arterial blood gas indexes such as carbon dioxide（PaCO2）and partial pressure of oxygen（PaO2）were measured，the ratio of lung wet/ dry mass（W /D）was determined，the inflammatory cell count in the bronchoalveolar lavage fluid（BALF）was detected，the histopathological feature in the lung tissues was observed by hematoxylin-eosin （HE） staining and the pathological injury was scored， enzyme-linked immunosorbent assay（ELISA）was used to detect myeloperoxidase（MPO）activity in the lung tissues and interleukin 6（IL-6）and cyclooxygenase 2（COX-2）levels in BALF and serum，and Western Blot was used to detect the expression of JAK2/STAT3 pathway key proteins in lung tissues. Results Compared with the sham-operated group，the model group rats showed that more obvious pathological injury in lung tissues was seen， and PaCO2 value，ratio of lung W/D，white blood cell count and eosinophils count in BALF，pathological injury score，MPO activity in lung tissues，IL-6 and COX-2 levels in BALF and serum，and ratios of p-JAK2/JAK2 and p-STAT3 / STAT3 in lung tissues were significantly increased，and PaO2 value was significantly decreased， the differences being statistically significant（P < 0.05）；compared with the model group，the emodin low- and high-dose groups rats showed that the pathological injury in lung tissues was reduced，PaCO2 value，ratio of lung W / D，white blood cell count and eosinophils count in BALF，pathological injury score，MPO activity in lung tissues，IL-6 and COX-2 levels in BALF and serum，and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in lung tissues were all decreased，and PaO2 value was increased，the differences being statistically significant（P < 0.05）， and the improvement effect was more stronger in high-dose emodin group； coumermycin attenuated the improvement effect of emodin on the above various indexes in the model rats. Conclusion Emodin can reduce the inflammation levels in SAP rats through inhibiting the activation of JAK2/STAT3 signaling pathway，thus reducing the lung tissue damage and improving the lung function of rats.

R285.5

河北省中医药管理局2022年度中医药类科研计划课题（编号：2022417）