慢性阻塞性肺部疾病(COPD)是全球性高发病率、高死亡率以及高卫生保健费用的重要疾病之一。2001年COPD是发达国家第5位的致死原因,占总死亡数的3.8%;在发展中国家则为第6位致死原因,占总死亡数的4.9%[1]。随着全球人口的老龄化,COPD负担将逐年增加。因此,在未来数年内我们必须共同面对挑战,实施有成本效益的防治策略,以遏制这一疾病及其耗费。
支气管哮喘是由嗜酸粒细胞、 肥大细胞和T淋巴细胞等多种细胞和细胞组分参与的气道慢性炎症性疾患,主要病理特点为上皮层大量的嗜酸粒细胞浸润及以上皮下纤维化、平滑肌增生、胶原蛋白沉积为主的气道重塑。哮喘的发病机制较为复杂,而炎症因子表达异常在哮喘的发病中发挥主要作用[1-3]。哮喘是一种全球范围内的常见病、多发病,我国约有1000万以上哮喘患者,而目前对于哮喘尚缺乏有效的根治方法。 间充质干细胞(mesenchymal stem cells,MSC)是具有强大的增殖能力和多向分化潜能的成体干细胞,同时具有免疫调节作用,它能通过免疫调节作用改善多种免疫相关性疾病的病情,而既往MSC在呼吸系统疾病中的研究主要集中在急性肺损伤,在哮喘当中的研究甚少。对于哮喘这一类以炎症因子表达异常为主的变态反应性疾病,MSC是否可以用于哮喘的治疗,值得我们进一步探讨。
ObjectiveTo study immunodepression effect of bone marrow-derived mesenchymal stem cell (BMSC) on acute asthmatic airway inflammation by galectin-1 (gal-1) in vivo.MethodsEighty-five female BALB/c mice were equally randomized into normal control group, asthmatic group, BMSC treatment group, gal-1 treatment group and BMSC and gal-1 inhibitor group. Ovalbumin (OVA) was used to establish acute asthmatic model. Total cell number and differential cell analysis in each group in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, hematoxylin-eosin and periodic-acid Schiff staining was used to compare airway inflammation among five groups. Measurement of cytokines, including interleukin (IL) -4, IL-5 and gal-1 in BALF and OVA specific IgE (OVA-IgE) in serum were evaluated by enzyme linked immunosorbent assay. Moreover, dendritic cell (DC) in lung tissue was sorted by immunomagnetic beads and its MAPK signal pathway was analyzed by western blotting among five groups.ResultsAccumulation of inflammation cells, particularly eosinophils around airway and in BALF was evident in asthmatic mouse model, meanwhile hyperplasia of Goblet cell was also obvious in asthmatic group. BMSC engraftment or gal-1 infusion significantly reduced airway inflammation and hyperplasia of Goblet cell and the number of inflammation cells in BALF, especially eosinophils attenuated dramatically. However, there was no effect on airway inflammation and hyperplasia of Goblet Cell by simultaneous infusion BMSC engraftment and gal-1 inhibitor. Compared to normal control group, the level of IL-4, IL-5 in BALF and OVA-IgE in serum was increased remarkably in asthmatic group, but the level of gal-1 reduced obviously. Moreover, infusion of BMSC or gal-1 could mitigate the level of IL-4, IL-5 in BALF and OVA-IgE in serum and increase the level of gal-1 in asthmatic mouse. However, infusion with both BMSC and gal-1 inhibitor exerted no effect on cytokine and OVA-IgE in asthmatic mouse. DC was sorted by immunomagnetic beads and western blotting was used to detect the expression of MAPK signal pathway among five groups. The expression of ERK phosphorylation in asthmatic group was much lower than that in normal control group. On the contrary, the expression of p38 phosphorylation was much higher than that in normal control group. BMSC engraftment or gal-1 infusion significantly activated the ERK pathway and inhibited the p38 MARP pathway on asthmatic mouse DC. Nevertheless, the expression of ERK phosphorylation and p38 phosphorylation for group with BMSC and gal-1 inhibitor infusion was between the level of asthmatic group and normal control group.ConclusionsBMSC infusion alleviates airway inflammation in asthmatic mouse, especially weakens eosinophils infiltration, and the underlying mechanism might be protective effect of gal-1 secreted by BMSC which plays a role in lung tissue DC and regulates the DC expression of MAPK signal pathway.
ObjectiveTo establish a simple and stable model of benign tracheal stenosis in SD rats by nylon brush scraping induced mechanical injury, and to observe the pathological changes of tracheal tissue at different time points after modeling.MethodsTwenty SD rats were divided into sham operation group (10 rats) and stenosis model group (10 rats) by random number method. Symptoms and survival conditions were observed, tracheal tissues were obtained, granulation tissue proliferation was observed, and stenosis indexes were measured and compared. Another fifteen rats were sacrificed at different time points (days 0, 2, 4, 6, and 8) after modeling. Tracheal tissues were obtained, HE staining and Masson staining were performed to observe pathological changes with time.ResultsThe survival rate of the sham operation group was 100% on the 8th day after operation, and the survival rate was 0% on the 8th day after operation in the stenosis model group. The difference in survival condition between the two groups was statistically significant (P=0.000 1) by Log-rank test. The stenosis index in the sham operation group was (6.12±1.78)%, and in the stenosis model group was (60.28±12.56)%. The difference in the stenosis between the two groups was statistically significant (P<0.000 01). HE staining results showed that the tracheal lumen was unobstructed and no granulation tissue hyperplasia or stenosis was found in the sham operation group. The epithelial mucosa was intact and smooth, and the cilia structure was clearly visible. It was a pseudo-stratified ciliated columnar epithelium, which was consistent with the characteristics of normal airway mucosa. While in stenosis model group, the lumen was significantly narrowed, and the stenosis was mainly caused by granulation tissue hyperplasia. No epithelial structure was observed, or epithelial structure was extremely abnormal. Masson staining showed that the fibroblasts in the injured site increased first and then decreased, and the collagenous fiber (blue) in the injured site gradually increased with time.ConclusionsA model of benign tracheal stenosis in rats can be successfully established by nylon brush scraping induced mechanical injury. The modeling method is simple, controllable and reproducible. The model can be widely used in the investigation of pathogenic mechanism for benign airway stenosis and efficacy exploration of new treatment.
ObjectiveTo explore the efficacy of community-acquired pneumonia (CAP) by tracheoscopy intervention altimeter and analyze and compare its financial burden.MethodsRetrospective analysis of 419 hospitalized patients with CAP was carried in respiratory medicine department of four hospitals from July 1, 2017 to August 31, 2018 (Changhai Hospital, Shanghai First People’s Hospital, Baoshan Branch of Shanghai First People’s Hospital, and Baoshan Integrated Traditional Chinese and Western Medicine Hospital). According to the time of tracheoscopy intervention treatment, they were divided into 3 groups: 127 patients treated with tracheoscopy intervention during the initial treatment period (within 72 h after obtaining imaging diagnosis) were included in an early intervention group, 158 patients treated with tracheoscopy intervention 72 h after obtaining imaging diagnosis were included in a medium-term intervention group, and 134 patients treated without tracheoscopy intervention were included in a non-intervention group. The total efficiency of treatment, improvement of clinical symptoms, imaging absorption, serum inflammation index level, sputum culture positive rate, change rate, efficiency after drug change, hospital stay and hospitalization cost were compared among three groups.ResultsThe total efficiency of treatment in the early intervention group was higher than that of the medium-term intervention group and the non-intervention group, with statistically significant difference (P<0.05), and the time of normality of body temperature, the time of disappearance of strong sputum and cough in the early intervention group, the absorption time of chest X-rays were shorter than that of the medium-term intervention group and the non-intervention group, and the difference was statistically significant (P<0.05); peripheral blood hemoglobin, serum calcitonin and hypersensitive C reactive protein levels were lower than those in the medium-term intervention group and the non-intervention group, with statistically significant differences (P<0.05), and the sputum-positive and drug-change rates in the early intervention group and the medium-term intervention group were higher than those in the non-intervention group, and the difference was statistically significant (P<0.05); the duration of hospital stay in the early intervention group was shorter than that of the medium-term intervention group and the non-intervention group, and the cost of hospitalization was less than that of the medium-term intervention group and the non-intervention group, and the difference was statistically significant (P<0.05).ConclusionTracheoscopy intervention treatment in the initial period of CAP not only significantly improves the efficacy, but also significantly reduces treatment costs and length of hospitalization, hence it is worth clinical promotion.