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Objective To explore the roles of Th17 cells in paraquat-induced acute lung injury(ALI)in a murine models through investigating the expression of Th17 type cytokine IL-17 and the specific transcription factor of Th17 cells-RORγt mRNA. Methods Male Kunming mice were randomly divided into the normal control group and the poisoned group. The ALI model induced by PQ poisoning was produced by intraperitoneal injection PQ solu-tion (20 mg/kg),and the normal control group was given normal saline solution with the same volume. After treatment for 48 hours,the animals were sacrificed. H&E staining and TUNEL staining were done to measure histo-logical changes and apoptosis. Serum level of Th17 related-cytokines was assayed by ELISA. The mRNA ex-pression of RORγt and the protein expression of IL-17 in the lung tissue were detected by real time-PCR assay and western blot,respectively. Results Compared with the normal control group,the lung inflammation and apopto-sis were significantly higher in the poisoned group. The serum level of IL-17A was significantly increased (P <0.05) and the lung parenchyma RORγt mRNA and IL-17 protein levels were significantly increased. Conclu-sion IL-17 plays an important role in the pathogenesis of ALI induced by paraquat poisoning.
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Aim To establish and compare asthma models among different strains of obese mice. Methods Different strains of SPF female mice, namely Kunming ( KM ) , C57BL/6J and BALB/c mice, were randomly divided into four groups ( control group, asthma group, obesity group and obese asthma group). The mice were fed a high-fat diet or a normal diet for 12 weeks, following which they were sensitized and challenged with ovalbu-min ( OVA) or phosphate-buffered saline ( PBS) . Body weight, fat weight, liver weight, Lee′s index, OVA-specific IgE concen-tration in bronchoalveolar lavage fluid ( BALF) , serum total cho-lesterol ( TC) and triglyceride ( TG) levels, and lung and adi-pose morphologies were evaluated. The specific airway resistance ( sRaw) was measured using double-chamber plethysmography. Results The mice on a high-fat diet showed a more rapid in-crease in body weight compared with those on a normal diet. Af-ter 12 weeks of feeding, body, fat, and liver weights and Lee′s index were higher for the obese mice than for the lean mice. The adipocyte cross-sectional area was significantly greater in the obese BALB/c and KM mice than in their lean counterparts;the C57BL/6J groups showed no significant differences. The BALB/c mice demonstrated more significant symptoms of acute asthma, local inflammation and airway hyper-responsiveness ( AHR ) . Conclusion Compared with C57BL/6J and KM mice, BALB/c mice fed a high-fat diet and sensitized and challenged with OVA provide the most suitable model for evaluating the relationship between obesity and asthma.
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Objective To introduce inhaled inactivated-mycobacterium phlei on prevention and treatment of moderate bronchial asthma to observe the clinical effect. Method This study was a prospective and controlled study. The patients diagnosed with asthma in our out-patient from March 2009 to December 2010 were collected, who met the following conditions were included in the study: age≥ 14 years; met the criteria of moderate chronic persistent bronchial asthma in Global Initiative for Asthma (GINA) in 2008; suspended receiving systemic corticosteroids, Montelukast, ketotifen and other anti-inflammatory and anti-allergic drugs in one month; no significant respiratory tract infections; and other serious illnesses or abnormalities known.A total of 100 patients with asthma were selected, including 37 males and 63 females, age (32.11 ± 12.95 )years. The patients were randomly(random number) divided into two groups: A group(treatment group; 16males and 34 females, age 33.56 ± 14.23 years) and B group (control group; 21 males and 29 females,age 30.66 ± 11.50 years); 50 in each group. No significant difference was noted between the two groups on age and gender composition. The patients in A group were treated with inhaled inactivated-mycobacterium phlei F. U. 36 Injection 1.72 μg/mL × 2 that adding 3 mL normal saline, once a day for 5 days. The patients in B group were treated with salmeterol xinafoate and fluticasone propionate powder for inhalation (50/100 μg), twice daily for sustainable use. The patients in the two groups were observed for one month. During this course, the patients in the two groups could inhale the salbutamol sulphate aerosol as need to relieve symptoms. And the number of using was recorded. Pulmonary function test and asthma provocative test were carried out on the Day O, 6 and 31. ACT scores were measured before and after the treatment. Results On Day 6 and 31 after treatment, the negative conversion rates of asthma provocative test of the patients in A group were 82% and 78% respectively, B group were 84% and 90% respectively. Provocative test of the patients in the two groups were negative conversion significantly before and after treatment. There was no significant difference between the two groups by chi-square test (P ＞ 0. 05 ). Completely random designed data was analyzed by analysis of variance. The analysis showed that the accumulated doses of methacholine of the patients in the two group increased significantly ( P ＜ 0. 05 ), but no difference between the two groups.There was a improvement trend on forced expiratory volume in one second( FEV1 )of the patients in A group after treatment, but no difference. FEV1 of the patients in B group increased significantly higher ( P ＜0.05), which was significantly higher than A group on the 31th day (P ＜0. 05); Peak expiratory flow (PEF) of the patients in the two group increased significantly on Day 6 and 31 after treatment (P ＜0.05 ).On Day 31, B group was significantly higher than A group ( P ＜ 0. 05 ); Scores of asthma control test (ACT)of the patients in the two group were significantly increased, and the number of using of salbutamol sulfate aerosol was significantly reduced (P ＜0.01 ). B group was obvious than group A (P ＜0.05 ). During treatment, there were only two adverse reaction cases of transient low fever; most obvious was on the third day.Conclusions Inhaled inactivated-mycobacterium phlei would inhibit the airway hyperresponsiveness of the patients with moderate bronchial asthma in short time, improve the symptoms, reduce the acute exacerbation, and reduce the use of rescue medication, which has the roles of prevention and treatment of moderate asthma in a certain period of time.
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Objective To investigate the modulatory effects of glycyrrhizin (GL) on the expressions of nu-clear factor kappa B (NF-κB), glucocorticoid receptor (GR) and cytokines in serum, and to explore the protective mechanism of GL in acute lung injury (ALI) induced by lipopolysaecharide (LPS). Method Twenty-four male Sprague-Dawley rats were randomly(random number) divided into three groups (n = 8 in each) : normal group, ALI group and GL treatment group. Rats in the ALI group and GL treatment group were administered with LPS (5 mg/kg) intravenously. In GL treatment group, rats were treated with GL (20 mg/kg) one hour before LPS injec-tion. The animals were sacrificed 4 hours after injection of LPS, and then the lung wewt/dry ratio and PaO_2 were measured, the histopathology of lung injury was observed under light microscope, the expressions of NF-κB mRNA and GR mRNA in lung tissues were detected by using RT-PCR, and the levels of NF-κB protein and GR protein were determined by using Western blot. The levels of TNF-α and IL-10 in serum were observed by using ELISA.Data were analyzed with SPSS version 13.0 software, and means were compared with analysis of variance and Stu-dent-Newman-Keuls test. Results (1) TNF-α levels in normal group, ALI group and GL treatment group were (43.96±7.57), (153.68±20.42), and (87.23±7.52) ng/L, respectively, and IL-10 levels were (24.72±8.03), (42.48±6.81) and (58.33±9.62) ng/L, respectively (F = 183.70, all P <0.01). (2) NF-κB mRNA expressions in normal group, ALI group and GL treatment group were (0.432±0.085), (3.414±0.521) and (1.894±0.272), respectively, and NF-κB protein levels were (45.6±7.3), (254.7±16.4)and (133.5 ±11.7) ng/L, respectively, and comparison between groups showed statistical significant (F = 187.82 and 1466.53, ALL P < 0.01). GR mRNA expressions in normal group, ALI group and GL treatment group were (0.434±0.013), (0.152±0.025) and (0.308±0.033), respectively, and GR protein levels were(54.6±6.5), (11.5±2.3)and (28.2±5.6) ng/L, respectively (F = 246.00 and 260.92, all P < 0.01). (3) Com-pared with normal group, infiltration of PMNs, capillary congestion and swelling were found in ALI group, and treatment with GL could attenuate the lung injury. Conclusions Glycyrrhizin has a protective effects on rats with ALI induced by LPS maybe through down-regulating the expressions of NF-κB mRNA and TNF-α mRNA, and up-regulating the expression of GR mRNA and level of IL-10 protein.
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AIM: To observe the changes of iNOS and eNOS in lung tissue and NO in bronchoalveolar lavage fluid (BALF) in smoking rats. METHODS: 80 Wistar rats were divided into control, smoking group, L-NIL group and L-NAME group (rats were exposed to smoke and injected (i.p.) with selective iNOS inhibitor L-NIL or NOS inhibitor L-NAME). iNOS and eNOS protein levels in whole lung were detected by immunohistochemical staining, and NOS mRNA was quantified using RT-PCR. In addition, NO - 2/NO - 3 was determined using Griess assay. RESULTS: The expression of iNOS mRNA and protein in smoking rats increased, the expression of eNOS mRNA and eNOS protein decreased, and the total cell count and the level of NO - 2/NO - 3in BALF increased( P