Objective To assess the variation and its significance of messenger ribonucleic acid(mRNA) expression of endothelial nitric oxide synthase (eNOS) in allografts of common carotid transplantation model in white rabbits. Methods To establish an animal model of common carotid transplantation in vivo, 30 rabbits were divided into four groups with random number table. Group A (n=3): autografts; group B (n=9): allografts with the least treated; group C (n=9): allografts treated by penicillin/streptomycin and preserved under room temperature; group D (n=9): allografts treated by penicillin/streptomycin and cryopreserved in liquid nitrogen. All the transplanted grafts were harvested 1-3 weeks later, then compared and evaluated the histomorphological variation and eNOS mRNA expression. Results The vascular structures of autografts in group A were kept approximately normal, only a few infiltration of inflammatory cells could be found. The structural variations of allografts in other trial groups behaved similarly as, intima proliferation in the 1st week, intima hyperplasia in the 2nd week, and both intima and media hypertrophy in the 3rd week. And also there seemed that luminal thrombosis could be found in all the allografts. Allografts in group B were destructed utmost the worst in all the groups. The expression of eNOS mRNA in allografts of group B was significantly less than that in other groups (Plt;0.05). Conclusion The down-regulation of eNOS mRNA expression might lead to intima hyperplasia and thrombosis of allografts.
Medical nitric oxide (NO) flow control system plays an important role in lowering pulmonary hypertension. The design requirements, overall scheme, delivery system and hardware circuits of a medical NO flow control system were introduced in this paper. Particularly, we proposed the design of NO delivery system and hardware circuits in detail. To deliver nitric oxide of a variable concentration, the designed system needs to work with a ventilator. The system can adjust and monitor the inhaled nitric oxide concentrations and send out sound and light alarms when the inhaled nitric oxide concentrations are out of the set range. To validate reliability and efficacy, we measured specifications such as linearity, stability and response time of the proposed NO flow control system by continuously administering nitric oxide into inspiratory circuit to deliver nitric oxide of variable concentrations to a test lung. The experiments showed that these specifications can meet the desired requirements.
Objective To study the relationship between the expression ratio of induced nitric oxide synthase (iNOS) over glial fibrillary acidic protein (GFAP) and the time of injury after brain concussion in rat, in order to acquire a new visual angle for determining injury time of cerebral concussion. Methods Eighty-five healthy Sprague-Dawley rats were divided into three groups randomly: model group (n=25), experimental group (n=55), and control group (n=5). The rats in the model group were used to confirm the attack hight to make the model of brain concussion; according to the time of execution, rats in the experimental group were then subdivided into 11 groups with 5 rats in each subgroup, and their execution time was respectively hour 0.5, 1, 3, 6, 12, 24, 48, 96, 168, 240, and 336; the rats in the control group were executed after fed for 24 hours. After the model of cerebral concussion was established through freefalling dart method, hematoxylin-eosin staining and immunohistochemistry staining of iNOS and GFAP were conducted for the brain of the rats. All related experimental results were studied by using microscope with image analytical system and homologous statistics. Results The ratio of positive expression of iNOS over that of GFAP increased gradually during hour 0.5- 3 after injury in brain (from 5.03 to 10.47). At the same time, the positive expression of iNOS increased significantly (from 14.61% to 37.45%). However, the increase of the positive expression of GFAP was not obvious. Between hour 3 and 12, the ratio began to decline to 4.98, which was still at a high level, and during the same time period, the positive expressions of iNOS and GFAP also experienced the same change pattern. Later, the ratio began to decline between hour 12 and 336 after injury (from 4.98 to 0.95). All ratios at this time were lower than those between hour 0.5 and 12. The positive expression of iNOS and GFAP both increased to a climax before declining. Conclusions The ratio of positive expression of iNOS over GFAP and the respective change pattern of iNOS and GFAP can be used as the evidence of estimating the injury time of cerebral concussion. We can use the ratio of two or more markers to provide a new visual angle for concluding the concussion injury time.
Objective To investigate the effect of inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine on pancreas islets cultured with cytokines TNF-α and IL-1β in rats. Methods Islets isolated from Wistar rats were purified and cultured. According to whether cytokines TNF-α, IL-1β and aminoguanidine were added into the medium respectively or not, islets were divided into 4 groups: cultured with islet only was taken as blank control group, cultured with TNF-α+IL-1β as cytokine group, cultured with aminoguanidine as aminoguanidine group, and cultured with TNF-α+IL-1β and aminoguanidine as aminoguanidine+cytokine group. NO level in culture medium and iNOS activity in islets tissue (Test Kit), apoptosis (TUNEL method) and viability of islets cell (acridine orange/ethidium bromide stain), and the function of islets (insulin release test) were measured. Results Compared with blank control group, the activity of iNOS in islet tissue and level of NO in culture medium increased, and the mass mortality and apoptosis appeared in islet cells, while insulin secretion decreased in cytokine group (P＜0.01). Compared with cytokine group, the activity of iNOS 〔（3.17±0.51） U/ml vs. （38.93±4.72） U/ml〕 and level of NO 〔（50.5±10.4） μmol/L vs. （313.0±35.4） μmol/L〕 decreased, the survival 〔（72.73±3.14）% vs. （57.07±5.07）%〕 increased and the apoptosis rate 〔（20.11±8.48）% vs. （41.17±6.87）%〕 decreased, the insulin secretion (secretion index: 3.50±0.27 vs. 1.96±0.19) improved； There were all significant differences in 2 groups (P＜0.01). Conclusion The iNOS inhibitor aminoguanidine could prevent the islet from the damage of iNOS/NO, alleviate the impairment of cytokines to islets, and ameliorate the survival and function of islets.
Objective To investigate the efficacy of low-dose inhaled nitric oxide (iNO) in the treatment of severe hypoxemia after Sun’s operation. Methods The clinical data of patients undergoing Sun’s operation for acute Type A aortic dissection in our hospital from January 2020 to June 2022 were retrospectively analyzed. Patients who received conventional treatment before November 2021 were enrolled as a control group. After November 2021, iNO was used in our hospital, and the patients who received iNO as an iNO group. The preoperative clinical baseline data, perioperative clinical data and oxygenation index were compared between the two groups. Results A total of 54 patients were included in the control group, including 45 males and 9 females, with an average age of 53.0±10.9 years. A total of 27 patients were included in the iNO group, including 21 males and 6 females, with an average age of 52.0±10.6 years. The preoperative body mass index of the two groups was greater than 25 kg/m2, white blood cell count, C-reactive protein were significantly higher than normal level, but there was no statistical difference between the groups (P＞0.05). There were no statistical differences in intraoperative data between the two groups (P＞0.05). The iNO group had significantly shorter duration of mechanical ventilation, postoperative ICU stay, and postoperative hospital stay than the control group (P<0.001). After 12 h of iNO treatment, hypoxic condition improved obviously, oxygenation indices in 12 h, 24 h, 36 h,48 h, 60 h and 72 h in the iNO group were significantly higher than those in the control group (P<0.05). Conclusion The treatment of severe hypoxemia after Sun’s surgery with low-dose of iNO is safe and effective, can significantly improve oxygenation function, and has significant advantages in shortening ventilator use time, postoperative ICU stay and postoperative hospital stay, but it is not significant in changing postoperative mortality.
ObjectiveTo investigate the effects of curcumin on expression of iNOS mRNA, study the protective and therapeutic effects on rats with severe acute panceratitis associated renal injury, and explore the possible mechanisms. MethodsA total of 24 rats were randomly divided into control group (n=8), severe acute panceratitis with renal injury group (injury group, n=8), and curcumin-treated group (treated group, n=8).The rats of control group and injury group were given 1.5 mL saline through intragastric administration at 3 h before operation, while the rats of treated group were fed with same amount of curcumin diluent at 3 h before operation.The rats of injury group and treated group with pancreatic head clamping method to establish the model of severe acute pancreatitis.At 12 h after modeling, rats in control group and injury group were perfused with 1.5 mL saline, and rats in treated group were intragastrically administrated to the same volume of curcumin diluent.All the rats were sacrificed at 18 h after modeling.The levels of serum amylase, creatinine, and blood urea nitrogen were detected and pathological chang of pancreas and the left kidney were observed under light microscope.The renal cell apoptosis were analyzed using TUNEL staining in three groups.The serum levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in three groups were detected by enzyme-linked immunosorbert assay (ELISA).The expressions of inducible nitric oxide synthase (iNOS) mRNA in the right kidney were detected with realtime polymerase chain reaction (RT-PCR) in three groups. ResultsCompared with the control group, the levels of serum amylase, creatinine, blood urea nitrogen, IL-1β, IL-6, and IL-10, the cell apoptosis and the expressions of iNOS mRNA in injury group and treated group were significantly increased (P < 0.05).In the treated group, the level of IL-10 was higher than the injury group (P < 0.05), and the difference of other indexes were lower than the injury group (P < 0.05). ConclusionsCurcumin has a better protective effect on severe acute pancreatitis associated renal injury.It may be through inhibited the expressions of IL-1βand IL-6, stimulated the expression of IL-10, and down-regulation of iNOS mRNA expression to reduce the generation of oxygen free radicals and NO damage to cell and reducing the cell apoptosis and necrosis of kidney.
Objective Observing the expressions of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） mRNA in lung tissues of rats with acute necrotizing pancreatitis （ANP） to explore the role of NOS in ANP associated-lung injury. Methods Forty Wistar rats were assigned into ANP group (n=30) and sham-operation group (SO group, n=10). ANP model was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Pathological changes of the lung tissue were observed under light microscope at 3 h, 6 h and 12 h after the ANP-model operation, and the expressions of iNOS mRNA and eNOS mRNA in lung tissue were assayed by RT-PCR. Results Different degrees of pathological changes of the lung tissue, such as hyperemia, edema, inflammatory cells infiltration, hemorrhage and necrosis, were found in the ANP group. The pathologic injury scores of lung tissue in ANP group were higher than that in SO group (Plt;0.05), and gradually increased with the duration extension of ANP (Plt;0.05). Compared with the SO group, the expressions of iNOS and eNOS mRNA in ANP group were all higher at 3 h, 6 h, and 12 h (Plt;0.05). Conclusions The overexpressions of iNOS and eNOS mRNA may play important roles in lung injury of ANP. This provides us a theory basis that lung injury of ANP could be relieved by inhibiting the expressions of iNOS and eNOS mRNA.
ObjectiveTo explore the predictive value of fractional exhaled nitric oxide (FeNO) in the treatment response of adult asthmatic patients. Methods64 adult outpatients with asthma from Peking Union Hospital between March and September 2013 were recruited in the study. All patients completed asthma control test (ACT) together with exhaled nitric oxide (FeNO) and pulmonary function test. Then the patients were classified into a higher FeNO group (n=33) and a normal FeNO group (n=31) according to FeNO level. All patients accepted regular inhaled ICS/LABA treatment (salmeterol and fluticasone 50/250). Three months later all patients reaccepted ACT,FeNO and pulmonary function test. ResultsThe ACT score increased in all patients,and was significantly higher in the higher FeNO group than that in the normal FeNO group[22.07±5.49 vs. 19.23±5.48,t=2.893,P<0.05]. The complete control rate of the higher FeNO group was higher than that in the normal FeNO group (42.42% vs. 19.35%,χ2=3.960,P<0.05). The FEV1 and FEV1%pred of two groups both increased significantly (P<0.05),but there was no significant difference between two groups (P>0.05). Correlation analysis showed that FeNO and the declined rate of FeNO was negatively correlated with the ACT score(r=-0.302,P<0.05;r=0.674,P<0.01) and positively correlated with the improvement of ACT score (r=0.514,P<0.01;r=0.674,P<0.01). No significant correlation was found between FeNO and FEV1 or FEV1%pred. ConclusionThe effect of ICS/LABA therapy is better for asthma patients with higher FeNO. FeNO can be used for predicting the response to ICS/LABA therapy in patients with asthma and guiding the treatment.
Objective To investigate the clinical characteristics of allergic and non-allergic asthma in Chinese adult asthmatic patients. Methods Consecutive treatment-naive adult outpatients with asthma were retrospectively analyzed in West China Hospital, Sichuan University from October 2014 to June 2016. The patients were classified into a non-allergic asthma (NAAS) group and an allergic asthma (AAS) group by skin prick test or antigen-specific IgE test. The differences between allergic and non-allergic asthma were compared in respect of gender, age, asthma control test (ACT) score, lung function, fractional exhaled nitric oxide (FeNO) level, body mass index (BMI), disease severity,etc. Results A total of 131 patients were enrolled in which 72 cases (54.96%) were allergic asthmatics and 59 cases (45.04%) were non-allergic asthmatics. The level of FeNO was statistically different (t=–2.762,P=0.007) between the NAAS group and the AAS group [(51.1±32.6)ppbvs. (69.1±41.7)ppb]. Seventeen cases of the NAAS group and 48 cases of the AAS group were complicated with rhinitis with statistically significant difference (χ2 =19.396,P=0.000). Airway limitation reversibility test showed that there were 37 cases in AAS and 20 cases in NAAS with no airway obstruction (NAO), 26 cases in AAS and 22 cases in NAAS with reversible airflow obstruction (RAO), 9 cases in AAS and 17 cases in NAAS with irreversible airflow obstruction (IAO), respectively, with statistically significant difference between two groups (Z=–2.461,P=0.014). There were 20 cases (33.9%) in NAAS and 37 cases (51.4%) in AAS with mild intermittent or persistent asthma, 18 cases (30.5%) in NAAS and 19 cases (26.4%) in AAS with moderate persistent asthma, 21 cases (35.6%) in NAAS and 16 (22.2%) in AAS with severe persistent asthma, respectively, with statistically significant difference (Z=–2.115,P=–0.034). The age, ACT score, FEV1%pred, and BMI had no statistical difference between two groups (allP>0.05). Conclusion Compared with allergic asthma, non-allergic asthma has less rhinitis, lower FeNO levels and higher prevalence of irreversible airflow obstruction.
Objective To review literatures regarding the diagnosis of asthma with the measurement of exhaled nitric oxide( eNO) and assess the effectiveness and accuracy of eNO in the diagnosis of asthma.Methods MEDLINE, OVID, CBMdisc, CNKI( 1991 to 2008) for studies involving the diagnostic value of eNO were searched, and references of included studies were also hand searched. QUADAS ( Quality Assessment of Diagnostic Accuracy Studies) items were used for quality assessment in the systematic review. Meta-disc software was used to analyze heterogeneity. Sensitivity, specificity and summary diagnostic odds ratio( SDOR) were used for the pooled analysis. The summary receiver operating characteristic ( SROC)curves were drew and the summary areas under the SROC ( SAUC) were calculated. Finally, sensitivity analysis was performed. Results Eleven literatures with15 studies were included. These 15 studies had well controlled the bias of partial verification, differential verification, incorporation and withdrawals. The possibility of the disease progression bias was less and the reference standard review could have a greater bias. The spectrumcomposition of a study, the inclusion and exclusion criteria and the reporting quality were poorly reported. In statistical analysis, the totally pooled sensitivity, pooled specificity, SDOR, SAUC of the measurement of eNO in the diagnosis of asthma was 0. 68, 0. 79, 12. 73, 0. 8446, respectively. Sensitivity analysis demonstrated no disproportionate influences of individual study. Conclusions eNO has a certain value in the diagnosis of asthma. To make further analysis, more studies with high quality are needed.