Effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease / 中华麻醉学杂志

Objective To evaluate the effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD).Methods Thirty adult male Sprague-Dawley rats,aged 8 weeks,weighing 200-250 g,were divided into 3 groups (n=10 each) using a random number table method:control group (C group),COPD group and doxofylline group (Dox group).Rats were fed in normoxia for 2 months,and normal saline 0.2 ml was injected into the trachea on 1st and 30th days in C group.Rats were exposed to cigarette smoke for 30 min every day,lasting for 2 months,and lipopolysaccharide 200 μg (0.2 ml) was injected into the trachea on 1st and 30th days in COPD and Dox groups.Two months later,rats in each group were anesthetized,tracheally intubated,and then mechanically ventilated.Doxofylline 50 mg/kg was intravenously injected immediately after intubation in Dox group,and the equal volume of normal saline was given instead in C and COPD groups.Pulmonary specimens were taken after 120 min of mechanical ventilation for examination of pathological changes and for determination of wet/dry weight ratio (W/D ratio) and tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents (by enzyme-linked immunosorbent assay).Results No significant pathological change of lung tissues was found in C group,and COPD pathological changes were observed in COPD and Dox groups.Compared with C group,the W/D ratio and TNF-α level were significantly increased,and the IL-10 level was decreased in COPD and Dox groups (P＜0.05).Compared with COPD group,the W/D ratio and TNF-α level were significantly decreased,and the IL-10 level was increased in Dox group (P＜0.05).Conclusion Doxofylline can reduce the pulmonary inflammatory response induced by mechanical ventilation in rats with COPD.

Evolution and mechanism of acute lung injury following hemorrhagic shock in a rodent model at plateau / 临床麻醉学杂志

Objective To explore the pathogenesis of acute lung injury in rats suffering hemorrhagic shock at plateau.Methods Seventy-two male Wistar rats, weighing 280-320 g, were randomized into 6 groups (n=12): sham group (group Sham), hemorrhagic shock for 15 min (group HS15), hemorrhagic shock for 30 min group (group HS30), hemorrhagic shock for 45 min group (group HS45), hemorrhagic shock for 60 min group (group HS60) and 90 min group (group HS90).Hemorrhagic shock model of Wistar rats was reproduced at plateau.The rats were only anesthetized, no shock and were sacrificed after 90 min in group Sham.The other groups were different in bleeding time and then were respectively sacrificed at 15, 30, 45, 60 and 90 min after shock.The pathological changes in the lungs were observed with light microscope.Wet to dry weight ratio (W/D), lung permeability index (LPI), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and superoxide dismutase (SOD) in lung were measured.Enzyme-linked immunosorbent assay was used to detect the TNF-α and IL-10 in lung tissue, the expression and distribution of claudin-3 and claudin-4 in lung tissue was verified by immunohistochemistry method.Results Compared with group Sham, shock causes acute lung injury at different degree, and was positively correlated with the duration of shock, during the period of 15 to 30 min, it merely rendered a slight change in lung W/D, LPI, MPO, MDA, TNF-α, T-SOD and IL-10.Subsequently, along with time prolonged, lung W/D, neutrophils in BALF, LPI, MPO, MDA, TNF-α were significantly elevated, while T-SOD and IL-10 were notably reduced (P<0.05).Immunohistochemical results showed that claudin-3 and claudin-4 expression in lung epithelial cells and endothelial cells expressed at low levels and dislocated (P<0.05).Conclusion After a short time compensatory lesions, the change of rats' hemodynamic stability suffering severe hemorrhagic shock showed a spiral downward.Along with the extension of the shock, hemorrhagic shock at plateau results into the disturbance of inflammatory response and oxidative stress, the loss of claudin-3 and claudin-4 in lung epithelial cells, which triggers the acute lung injury.

Efficacy of add-on montelukast in nonasthmatic eosinophilic bronchitis: the additive effect on airway inflammation, cough and life quality / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy of montelukast (MONT), a cysteinyl leukotriene receptor antagonist, in nonasthmatic eosinophilic bronchitis (NAEB), especially its influence on cough associated life quality is still indefinite. We evaluated the efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in improving life quality, suppressing airway eosinophilia and cough remission in NAEB.</p><p><b>METHODS</b>A prospective, open-labeled, multicenter, randomized controlled trial was conducted. Patients with NAEB (aged 18-75 years) were randomized to inhaled BUD (200 μg, bid) or BUD plus oral MONT (10 μg, qn) for 4 weeks. Leicester cough questionnaire (LCQ) life quality scores, cough visual analog scale (CVAS) scores, eosinophil differential ratio (Eos), and eosinophil cationic protein (ECP) in induced sputum were monitored and compared.</p><p><b>RESULTS</b>The control and MONT groups contained 33 and 32 patients, respectively, with similar baseline characteristics. Significant with-in group improvement in CVAS, LCQ scores, Eos, and ECP was observed in both groups during treatment. After 2-week treatment, add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement (both P < 0.05). Similar results were seen at 4-week assessment (both P < 0.05). 4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and greater decrease of ECP (both P < 0.05).</p><p><b>CONCLUSIONS</b>MONT combined with BUD was demonstrated cooperative effects in improvement of life quality, suppression of eosinophilic inflammation, and cough remission in patients with NAEB.</p>

Effect of suberoylanilide hydroxamic acid on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude / 中华麻醉学杂志

Objective To evaluate the effect of suberoylanilide hydroxamic acid (SAHA) on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude.Methods Forty healthy male SpragueDawley rats,aged 2-3 months,weighing 240-280 g,transported from breeding grounds at an altitude of 1520 meters to the experimental station at an altitude of 3780 meters,were randomly divided into 4 groups (n =10each):sham operation group (group S),lethal hemorrhagic shock group (group LHS),normal saline group (group NS),and SAHA group.Anesthesia was induced with inhalation of 3% isoflurane and maintained with inhalation of 0.5%-1.0% isoflurane.Lethal hemorrhagic shock was induced by withdrawing blood from the femoral artery in groups LHS,NS and SAHA.Normal saline 0.25 ml and SAHA 7.5 mg/kg (0.25 ml) were injected intravenously over 2 min after completion of blood-letting in groups NS and SAHA,respectively.The survival rates with 3 h were recorded.Blood samples from femoral veins were taken before blood-letting,immediately after completion of blood-letting and at 3 h after completion of blood-letting (immediately after death if the survival time was less than 3 h) for determination of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) activities by the colorimetric method.Liver specimens were taken at 3 h after completion of blood-letting or immediately after death for examination of the pathological changes of the liver and for determination of c-Jun N-terminal kinase (JNK),phosphorylated-JNK (p-JNK) and caspase-3 expression and acetylation of H3K9 in liver tissues by Western blot.Results Compared with group S,the activities of serum AST,ALT and LDH were significantly increased in the other three groups (P ＜ 0.01).Compared with LHS and NS groups,the activities of serum AST,ALT and LDH were significantly decreased,the survival rate within 3 h and acetylation of H3K9 were increased,caspase-3 expression was down-regulated,and p-JNK/JNK ratio was decreased in group SAHA (P ＜ 0.05 or 0.01).The pathological changes of the liver were severe in LHS and NS groups and attenuated in SAHA group.Conclusion Administration of SAHA in early shock can significantly protect the liver after lethal hemorrhage in rats first entering high altitude,and increased acetylation of H3K9 and inhibition of the JNK/caspase-3 apoptotic pathway in liver tissues are involved in the mechanism.

Research progress of histone deacetylase inhibitors in the theraphy of anti-sepsis shock in animal experiments / 国际外科学杂志

It has demonstrated histone deacetylase inhibitor to be protective in preclinical and early clinical studies for the therapy of cancer,central nervous system degenerative diseases and immune system diseases.Strikingly,Recent studies have shown that it has emerged as a potent prosurvival and anti-inflammatory drug,offering new lines of therapeutic intervention for sepsis shock,and can reverse the changes of genes expression at the molecular level,caused by sepsis shock and its follow-up of fluid resuscitation.What' s more,it has slight impact on hemodynamics,ultimately alleviates lesions to systemic inflammatory response syndrome and multiple organ failure syndrome and simultaneously lays a good foundation to win the golden time for treatment.On the other hand,with the development of second hit theory,it will also set up a bridge between hemorrhagic shock and septic shock,resulting in expansioning the breadth and depth of understanding of shock.In brief,histone deacetylase inhibitors are the extension and challenges of the traditional therapy of anti-sepsis shock.