茯苓酸调节IL-6/JAK2/STAT3信号通路对肺炎支原体肺炎小鼠的治疗作用研究  

Study on the therapeutic effect of pachymic acid on regulating IL-6/JAK2/STAT3 signaling pathway in rats with mycoplasma pneumoniae pneumonia

作　　者：赵之寒 刘卓 赵峥[2] 张亮亮[2] 靳兆 ZHAO Zhihan;LIU Zhuo;ZHAO Zheng;ZHANG Liangliang;JIN Zhao(Department of Thoracic Surgery,Western Area of Handan Central Hospital,Handan,Hebei 056000,China;Department of Respiratory Medicine,Western Area of Handan Central Hospital,Handan,Hebei 056000,China)

机构地区：[1]河北省邯郸市中心医院西区胸外科,河北邯郸056000 [2]河北省邯郸市中心医院西区呼吸内科,河北邯郸056000

出　　处：《检验医学与临床》2024年第24期3675-3681,共7页Laboratory Medicine and Clinic

基　　金：河北省医学科学研究课题(20220022)。

摘　　要：目的分析茯苓酸调节白细胞介素(IL)-6/酪氨酸激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路在肺炎支原体肺炎(MPP)小鼠治疗中的作用。方法将60只小鼠按照随机数字表法分为对照(CK)组、模型(Model)组、茯苓酸低剂量组、茯苓酸高剂量组、茯苓酸高剂量+Colivelin(JAK2激活剂)组、Fedratinib(JAK2抑制剂)组。采用血气分析仪检测动脉血中氧分压(PaO_(2))、二氧化碳分压(PaCO_(2)),并计算氧合指数(OI);检测肺组织湿/干(W/D)比值;采用酶联免疫吸附试验检测肺组织中肿瘤坏死因子-α(TNF-α)、IL-10、IL-18水平;采用苏木精-伊红(HE)染色观察肺组织病理损伤;采用原位末端标记(TUNEL)染色检测肺组织细胞凋亡情况;采用蛋白印迹法检测小鼠肺组织中B淋巴细胞瘤-2关联X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)、IL-6、磷酸化酪氨酸激酶2(p-JAK2)/JAK2、磷酸化信号传导子及转录激活子3(p-STAT3)/STAT3蛋白表达水平。结果CK组小鼠肺组织形态结构正常;与CK组比较,Model组小鼠肺组织结构明显被破坏,动脉血中PaCO_(2)、肺组织W/D比值、TNF-α及IL-18水平、凋亡率,以及Bax、IL-6、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平明显升高,动脉血中PaO_(2)、OI,以及肺组织IL-10水平、Bcl-2蛋白表达水平明显降低,差异均有统计学意义(P<0.05);与Model组比较,茯苓酸低剂量组、茯苓酸高剂量组和Fedratinib组小鼠肺组织形态有所改善,动脉血中PaCO_(2)、肺组织W/D比值、TNF-α及IL-18水平、凋亡率,以及Bax、IL-6、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达水平明显降低,动脉血中PaO_(2)、OI,肺组织IL-10水平、Bcl-2蛋白表达水平明显升高,差异均有统计学意义(P<0.05)。结论茯苓酸可降低MPP小鼠肺组织炎症反应和细胞凋亡,改善肺组织功能,可能与抑制IL-6/JAK2/STAT3信号通路有关。Objective To analyze the role of pachymic acid in regulating the interleukin(IL)-6/tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in the treatment of Mycoplasma pneumoniae pneumonia(MPP)mice.Methods Sixty mice were randomly divided into control(CK)group,model group,low-dose pachymic acid group,high-dose pachymic acid group,high-dose pachymic acid+Colivelin(JAK2 activator)group,and Fedratinib(JAK2 inhibitor)group according to a random number table.Blood gas analyzer was used to detect in arterial blood partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PaCO_(2))and calculates oxygenation index(OI).The wet/dry(W/D)ratio of lung tissue was detected.Enzyme linked immunosorbent assay was used to detect the levels of tumor necrosis factor-α(TNF-α),IL-10 and IL-18 in lung tissue.Hematoxylin-eosin(HE)staining was used to observe pathological damage in lung tissue.Apoptosis in lung tissue cells was detected using in situ end labeling(TUNEL)staining.Western blot was used to detect the protein expression levels of Bax,Bcl-2,IL-6,p-JAK2/JAK2,p-STAT3/STAT3 in mouse lung tissue.Results The lung tissue morphology and structure of the CK group mice were normal.Compared with the CK group,the lung tissue structure of the model group mice was significantly disrupted,and the levels of PaCO_(2)in arterial blood,lung tissue W/D ratio,TNF-α,IL-18,apoptosis rate,Bax,IL-6,p-JAK2/JAK2 and p-STAT3/STAT3 protein expression levels increased significantly.The levels of PaO_(2),OI,lung tissue IL-10 and Bcl-2 protein expression in the blood decreased significantly,the differences were statistically significant(P<0.05).Compared with the model group,the low-dose pachymic acid group,high-dose phchymic acid group and Fedratinib group showed improvement in lung tissue morphology in mice.The levels of PaCO_(2)in arterial blood,lung tissue W/D ratio,TNF-α,IL-18,apoptosis rate,Bax,IL-6,p-JAK2/JAK2 and p-STAT3 protein expression levels reduced significantly,while the levels o

关 键 词：茯苓酸 IL-6/JAK2/STAT3信号通路 肺炎支原体肺炎 B淋巴细胞瘤-2 肺组织 

分 类 号：R392.1[医药卫生—免疫学]