现已认识到免疫反应、转录因子核因子κB( NF-κB) 的激活、细胞因子、中性粒细胞的激活和肺泡渗入、凝血级联反应、肾素-血管紧张素系统等多种因素构成的复杂网络参与急性肺损伤/急性呼吸窘迫综合征( ALI/ARDS) 的发病过程[ 1-5] 。虽然脓毒症、创伤、肺炎等ALI/ARDS诱发因素很常见, 但仅有部分病人发生ALI/ARDS, 并且具有相似临床特征的ALI/ARDS病人可有截然不同的结果, 这种异质性引起研究者对影响ALI/ARDS 易感性和预后的遗传因子进行鉴别的浓厚兴趣[ 6] 。由于数量庞大的表现型变异, 不完全的基因外显率、复杂的基因-环境相互作用及高度可能的基因座不均一性而使ALI 遗传学的研究受到挑战[ 7] 。近年来基因组学技术被应用于ALI/ARDS 发病机制的研究, 加深了人们对ALI/ARDS的认识并有可能发展出新的治疗策略以降低其发病率和病死率。
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To investigate the blood clotting dysfunction of invasive pulmonary aspergillosis(IPA)and the therapeutic effect of low molecular hepafin in a mouse model．Methods The neutropenic IPA mouse model was constructed by being given cyclophosphamide to depress immunologic function，and then intranasally challenged with Aspergillus fumigatus conidia．(1)Blood clotting function were assessed by bleeding time，clotting time，platelet count and antithrombase-III(AT-III)activity．Seventy-two mice were randomly assigned into 4 groups．Group A received only normal saline．group B received normal saline to substitute the cycloph0sphamide，and the rest equal to group D．Group C received normal saline to substitute the AspergiUus fumigatus conidia suspension，and the rest equal to group D．Group D(model group)received cyclophosphamide(intraperitoneally，150 mg／kg，d4，d1)and Aspergillus fumigatus conidia suspension(intranasally，40 μL／mouse，1．5×10∧5／mL，d0)．Six mice were randomly sacrificed in each group for analysis of blood clotting function per 24 h after inoculation for 3 times．(2)Therapeutic effect of low molecular heparin was determined by survival time of IPA mice．One hundred and eighteen mice were randomly assigned into 4 groups after challenged with 6×10 conidia／mouse and received one of the following regimens daily from dl to d7 after challenge，vehicle(group E，n=29)，low molecular heparin(group F，n=30，subcutaneous injection，1000 IU／kg，qd×7 d)，amphotericin B(group G，n=29，intraperitoneal，1 m kg，qd×7 d)，low molecular heparin plus amphotericin B(group H，n=30)．Mice survivals were recorded once daily to d21 after innoculation．Results (1)AT-III activity of group D decreased significantly 24 h after innoculation．Bleeding time and clotting time decreased significantly and AT—III activity decreased sequentially 48 h after innoculation．The platelet decreased significantly 72 h after innoculation，and bleeding time shoaened further．Clotting time was longer than that 0f 48 h．but still shorter than norm al and AT-III activity decreased sequentially．There were significant differences when comparing group D with group A，B and C(all Plt;0.01)．And there was no significant difference between group A，B and C(all Pgt;0．05)．(2)Survival analysis indicated that the therapeutic effect of low molecular hepafin plus amphotericin B was better than that of amphotericin B or low molecular heparin alone．No therapeutic effect was found in group F(group E vs group F，Pgt;0．05，both group E and group F compared with group H，P lt;0．01．Group H vs group G，P lt;0．05．Both group E and group F compared with group G，P lt;0．05)．Conclusions The results suggest that there is blood clotting dysfunction in IPA mice and AT—III activity may be an early index to monitor the disfunction．Compared with the therapeutic effect of amphoterinein B alone，low molecular hepafin plus amphoterincin B can prolong survival of neutropenic IPA mice