弥漫性肺泡出血致病机制及弥漫性肺泡出血小鼠应用地塞米松治疗的效果  

Pathogenesis of diffuse alveolar hemorrhage in mice and the effect of dexamethasone

作　　者：杨中南 阎磊 曹慧霞 焦晓静 李纳 邵凤民 YANG Zhongnan;YAN Lei;CAO Huixia;JIAO Xiaojing;LI Na;SHAO Fengmin(Department of Nephrology,Zhengzhou University People's Hospital,Henan Provincial People's Hospital,Henan Provincial Key Laboratory of Kidney Disease and Immunology,Zhengzhou450003,China)

机构地区：[1]郑州大学人民医院河南省人民医院肾内科河南省肾脏病免疫重点实验室,郑州450003

出　　处：《中华实用诊断与治疗杂志》2020年第3期254-257,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省自然科学基金(182300410296);河南省科技厅重大科技攻关项目(121100910600)。

摘　　要：目的探讨弥漫性肺泡出血(diffuse alveolar hemorrhage, DAH)的可能发病机制及地塞米松治疗DAH模型小鼠的疗效。方法 C57BL/6小鼠30只,随机分为对照组、模型组、地塞米松组各10只。模型组、地塞米松组一次性腹腔注射Pristane 0.5 mL制备DAH模型,对照组一次性腹腔注射生理盐水0.5 mL。造模成功后,地塞米松组腹腔注射地塞米松15 mg/kg,模型组、对照组腹腔注射等量PBS,均1次/d,连续13 d。药物处理第14天处死3组小鼠,取肺组织,观察肺组织出血情况、肺组织病理改变,Western blot法检测肺组织磷酸化Janus激酶2(phosphorylation-Janus kinase 2, p-JAK2)、磷酸化信号转导和转录活化因子3(phosphorylation of signal transduction and activator of transcription 3, p-STAT3)相对表达量,TUNEL法检测肺组织细胞凋亡率。结果药物处理第14天,对照组肺组织呈正常乳白色、未见出血,组织病理示肺组织正常,未见炎症细胞浸润;模型组、地塞米松组肺组织呈暗红色,可见弥漫性出血,组织病理示肺泡腔内充满大量红细胞并伴有炎症细胞浸润,且模型组与地塞米松组无明显差异。模型组、地塞米松组肺组织p-JAK2相对表达量(0.147±0.010、0.153±0.007)、p-STAT3相对表达量(0.120±0.010、0.123±0.014)及肺组织细胞凋亡率[(7.794±1.116)%、(7.536±0.851)%]均高于对照组[0.056±0.006、0.045±0.009、(0.571±0.193)%](P<0.05),模型组与地塞米松组比较差异无统计学意义(P>0.05)。结论肺组织细胞凋亡增多及JAK2/STAT3活化可能与DAH发病相关,地塞米松对DAH无明显治疗作用。Objective To investigate the pathogenesis of diffuse alveolar hemorrhage(DAH) and the effect of dexamethasone on DAH mice models. Methods Thirty C57 BL/6 mice were randomly divided into control group, model group and dexamethasone group, with 10 mice in each group. Model and dexamethasone groups were intraperitoneally injected with 0.5 mL of pristane once to establish DAH mice models, while control group was intraperitoneally injected with equivalent volume of normal saline. After successful modeling, dexamethasone group was intraperitoneally injected with 15 mg/kg dexamethasone, while model and control groups were intraperitoneally injected with equivalent volume of PBS once a day totally for 13 consecutive days. The mice were sacrificed on the 14 th day after drug treatment to obtain the lung tissues. The hemorrhage and histopathologic change of lung tissues were observed in three groups. Western blot was used to detect the relative expressions of phosphorylation-Janus kinase 2(p-JAK2) and phosphorylation of signal transduction and activator of transcription 3(p-STAT3). TUNEL was used to detect the apoptotic rate. Results On the 14 th day after drug treatment, the lung tissue was in milky white, no hemorrhage was found, histopathologic examination showed normal lung tissue, and no inflammatory cell infiltration occurred in control group. The lung tissue was in dark red, diffuse hemorrhage was found, histopathologic examination showed a large amount of red blood cells in alveolar cavity and inflammatory cell infiltration occurred in model and dexamethasone groups, which showed no significant difference between two groups. The relative expressions of p-JAK2(0.147±0.010, 0.153±0.007), p-STAT3(0.120±0.010, 0.123±0.014) and lung cell apoptotic rates((7.794±1.116)%,(7.536±0.851)%) were higher in model group and dexamethasone group than those in control group(0.056±0.006, 0.045±0.009,(0.571±0.193)%)(P<0.05), and showed no significant differences between model group and dexamethasone group(P>0.05). Conclusion

关 键 词：弥漫性肺泡出血 细胞凋亡 磷酸化Janus激酶2 磷酸化STAT3转录因子 地塞米松 

分 类 号：R563[医药卫生—呼吸系统]