Objective:To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3)-retinoic acid-related orphan receptor gamma t (RORγt)-interleukin-17(IL-17) signaling pathway in airway inflammation in neutrophil asthma mice.Methods:This was an experimental study.A total of 36 female BALB/C mice were randomly divided into three groups: neutrophilic asthma group, eosinophilic asthma group, and normal control group.The eosinophilic asthma model was sensitized by intraperitoneal injecting ovalbumin (OVA) and challenged with an aerosol of OVA.The neutrophilic asthma model was sensitized by OVA and intranasal infusion of lipopolysaccharide, challenged with an aerosol of OVA.The normal control group was sensitized and challenged by normal saline instead of OVA.Bronchoalveolar lavage fluid (BALF) was collected and the total number of the cells was counted.After HE staining, the cells were classified and the numbers counted.Pathological changes of lung tissue were observed after HE staining, STAT3 and RORγt were detected by immunohistochemistry, and the proportion of Th17 cells in lung tissue was detected by flow cytometry.The levels of IL-17 and IL-6 in serum and BALF were detected by enzyme linked immunosorbent assay.Results:Compared with normal control group, the eosinophilic asthma group had significant airway inflammatory cell infiltration, increased total number of BALF cells and proportion of neutrophils ( P<0.01), raised levels of IL-17 and IL-6 in BALF and serum ( P<0.05), and elevated proportion of CD4 + IL-17 + T cells ( P<0.01). Compared with the eosinophilic asthma group, the neutrophilic asthma group showed increased airway inflammatory cells, elevated total number of BALF cells and proportion of neutrophils ( P<0.05), decreased proportion of eosinophils ( P<0.05), increased levels of IL-17 and IL-6 in serum and BALF, and enhanced proportion of CD4 + IL-17 + T cells ( P<0.05). Compared with the normal control and eosinophilic asthma groups, the neutrophilic asthma group manifested elevated expressions of STAT3 and RORγt in lung tissue ( P<0.05). Conclusions:STAT3-RORγt-IL-17 signaling pathway is involved in the pathogenesis of different inflammatory phenotypes of asthma and plays a more important role in the pathogenesis of neutrophilic asthma.

目的 检测慢性肺源性心脏病(肺心病)急性加重期血浆N-端脑钠肽前体(NT-proBNP)含量,探讨其临床意义.观察冻干重组人脑利钠肽(rhBNP)治疗肺心病急性加重期的临床疗效.方法 选择我科2019年1月至2020年12月收治的肺心病急性加重期患者184例,同期收住我科的其他呼吸系统疾病患者184例作为对照组,测定两组NT-proBNP含量并进行比较.肺心病组NT-proBNP含量<1000 pg/mL的54例,(1000～2000)pg/mL之间40例,>2000 pg/mL 90例,比较不同含量对应心功能分级情况.含量>2000 pg/mL患者随机分为药物组和对照组,两组在常规氧疗、抗感染、平喘、祛痰等治疗基础上,药物组加用rhBNP,比较两组临床疗效.同时,再测定药物组患者治疗后NT-proBNP含量,比较治疗前后变化.结果 肺心病组和对照组的NT-proBNP浓度分别为(2068±975)pg/mL和(731±329)pg/mL,组间比较差异有统计学意义(P<0.05);肺心病组NT-proBNP含量<1000 pg/mL心功能为Ⅱ级,(1000～2000)pg/mL心功能为Ⅲ级,>2000 pg/mL心功能为Ⅳ级;药物组和对照组总有效率分别为97.8％和82.2％,组间比较差异有统计学意义(P<0.05);药物组治疗前后NT-proBNP含量分别为(3547±1486)pg/mL和(625±413)pg/mL,组内比较差异有统计学意义(P<0.01).结论 测定NT-proBNP含量有助于早期诊断肺心病心力衰竭和评估心力衰竭严重程度,为调整治疗方案提供科学依据.同时对肺心病心力衰竭疗效评估及预后判断有重要意义.rhBNP治疗肺心病急性加重期心力衰竭疗效确切,不良反应少,值得临床推广应用.

Objective To established chronic intermittent hypoxic (CIH) animal model for investigate the mechanism of insulin resistance caused by CIH.Methods Twenty-four healthy male SD rats were randomly divided into four groups:normal control group (NC group),CIH 2 weeks group (CIH2 group),and CIH 5 weeks group (CIH5 group),with 8 rats in each group.The minimum oxygen concentration was 6％-7％ in animal chamber.About 8 hours per day (from 9AM to 5 PM),the experimental lasted for 35 days.The rats in control group were placed in the same animal box without CIH.After the experiment,to measure fasting blood glucose and insulin levels by radioimmunoassay and then according to the homeostasis model of insulin resistance index (HOMA) was calculated.The expressions of SOCS3 protein were detected with immunohistochemical method in rat liver cells.To detect the SOCS3-mRNA gene expression by reverse transcription and polymerase chain reaction (RT-PCR).Results Compared with the NC group,fasting blood glucose(F =33.582,P ＜0.05),insulin level (F =35.633,P ＜0.05) and HOMA-IR (F =49.045,P ＜0.05) of the CIH2.CIH5 group was higher than other groups (P ＜0.05).Compared with the NC group,the expression of SOCS3 protein was increased in CIH2 and CHI5 group (F =9.472,P ＜0.05),but in CIH2 and CIH5 group were no significantly differences (P ＞0.05).And then the expression of SOCS3-mRNA in CIH5 was higher than CIH2 and CIH5 group (F =8.665,P ＜ 0.05).Pearson correlation analysis showed that HOMA-IR and the expression of SOCS3 protein was negatively correlated (r =-0.759,P ＜0.001) and was positively correlated with SOCS3-mRNA (r =0.603,P =0.01).Conclusions ①CIH exposure caused fasting blood glucose level and increase insulin level and insulin resistance in rats with CIH.With the intermittent hypoxic exposure time prolonged,the degree of insulin resistance was increased.②CIH leads to increased expression of SOCS3 protein and SOCS3-mRNA gene in rat liver cells with CIH exposure,SOCS3 may be involved in the development of insulin resistance.