Objective To study the inhibitory effects of curcumin on bleomycin-induced pulmonary fibrosis in rats at the fibrosing stage and explore its possible mechanism.Methods 96 male SD rats were randomly divided into a normal control group，a fibrosis model group，a fibrosis model treated with prednisone group and a fibrosis model treated with curcumin group.Pulmonary fibrosis were induced by instilled bleomycin through tracheal.From day 15 after bleomycin administration，the curcumin group and prednisone group were given curcumin（300 mg/kg） or prednisone（5 mg/kg） per day by intragastric administration，respectively.The normal control group and fibrosis model group were given 1% sodium carboxymethyl cellulose（10 mL/kg） as control.Six rats of each group were randomly sacrificed on day 21，28，42 and 56 after bleomycin administration，respectively.The histological changes of the lung were evaluated by HE and Masson’s trichrome staining.Lung expressions of transforming growth factor-β1（TGF-β1） and hydroxyproline were assessed by immuno-histochemistry and digestion method，respectively.Results Pulmonary fibrosis and hydroxyproline level in the curcumin group were significantly reduced as compared with those in the model group on day 42 and 56.The expession of TGF-β1 in the curcumin group was significantly lower than that in the model group on day 28，42 and 56，and was not significantly different from the normal group on day 56.Conclusion Curcumin could alleviate bleomycin-induced pulmonary fibrosis in rats at the fibrosing stage by inhibiting the expressions of TGF-β1.
Objective To study the pathology and possible mechanism of experimental hydrochloric acid（HCl） inhalation-indued pulmonary fibrosis in rats.Methods 120 male SD rats were randomly divided into a nomal control group，a bleomycin group，a high dose HCl group，a middle dose HCl group and a low dose HCl group.The bleomycin group was intratracheally injected with bleomycin once to induce pulmonary fibrosis.The three HCl groups were intratracheally injected with HCl once per week.The control group was given saline by the same way.Six rats of each group were randomly sacrificed on day 7，14，28 and 42 respectively.The histological changes of lung tissue were studied by HE and Masson’s trichrome staining.Hydroxyproline level in lung tissue was measured by digestion method.Protein and mRNA expression of transforming growth factor-β1（TGF-β1） were assayed by immunohistochemistry and RT-PCR respectively.Results Alveolitis in three HCl groups was significantl compared to control group，most severe at the second week，then remained at a high level which was equivalent to or exceeded the level of the bleomysin group after 28 days.Pulmonary fibrosis in three HCl groups was also significantly more severe than that in the control group，but milder than that in the bleomysin group.The high-dose and middle-dose HCl groups were not significantly different from the bleomysin group on day 42.There was no difference between three HCl groups in the earlier period，but the high-dose HCl group has a significantly difference from low-dose group on day 42.The content of hydroxyproline in high-dose and middle-dose HCl groups was also significantly higher than that in the control group.On day 42 hydroxyproline content in high-dose HCl dose rather middle –or low dose group was similiar with the level of bleomysin group.Content of TGF-β1 mRNA in three HCl groups was comparable to the level of bleomysin group on day 28 and exceeded on day 42.The expression of TGF-β1 in three HCl groups was not significantly different from the bleomysin group on day 42.Conclusion Experimental acid aspiration might contribute to pulmonary fibrosis in rats.Acid induced alveolar epithelial cell damage，abnormal proliferation and repair and fibrosis could be involved..
Objective To evaluate the diagnostic value and safety of surgical lung biopsies ( SLB)in patients with interstitial lung disease ( ILD) . Methods A retrospective analysis was performed on patients undergoing SLB, who were obtained from Chinese literatures through searching PubMed, CBM,Wanfang database, VIP information and CHKD from 2000 to 2010. The data from Affiliated Drum Tower Hospital, Nanjing University Medical College from2000 to 2010 was also reviewed. Results A total of 398cases underwent SLB, including open lung biopsy ( OLB) in 221 cases and video-assisted thoracoscopic lung biopsy ( VATLB) in 177 cases. SLB yielded a specific diagnosis for 386 cases. The total postoperative complication rate was 12. 1% and mortality rate was 2. 0% . The diagnostic yield, post-operative complication rate, and mortality rate between VATLB and OLB had no significant difference. Conclusion SLB is a useful and relatively safe procedure for diagnosis of ILD.
Objective To investigate the proliferation inhibitory effect and to explore the molecular mechanism of curcumin on pulmonary fibroblasts. Methods Fibroblasts derived from lung tissue of patients with idiopathic pulmonary fibrosis ( IPF) was cultured in vitro and incubated with curcumin at different concentrations for different time. Fibroblasts were randomized into 5 groups, ie. a control group and 4 curcumin groups ( intervened by 5, 10, 20, 40 μmol / L curcumin, respectively) . MTT assay was used to determine the inhibitory rate of curcumin on the proliferation of pulmonary fibroblasts. Apoptosis and the Caspase-3 expression of pulmonary fibroblasts were identified by flow cytometry ( FCM) . Variables were compared with One-Way ANOVA. The correlations between variables were analyzed using Pearson’scorrelation coefficient. Results Curcumin inhibited pulmonary fibroblasts proliferation in a dose-dependent and time-dependent manner( r =0. 886, r = 0. 832, respectively, all P lt; 0. 01) . Apoptosis rate of pulmonary fibroblasts in 4 curcumin groups was ( 29. 58 ±2. 13) % , ( 64. 36 ±3. 92) %, ( 72. 98 ±4. 42) % , ( 83. 14 ±2. 51) % , respectively, which was significantly higher than that in the control group[ ( 3. 84 ±1. 88) % , P lt;0. 01] . The positive expression rate of apoptosis-regulating protein caspase-3 was ( 26. 24 ±3. 64) % ,( 44. 87 ±5. 31) % , ( 57. 44 ±4. 23) % , ( 73. 65 ±5. 01) % , respectively, which was significantly higher than that of the control group[ ( 4. 02 ±0. 62) % , P lt; 0. 01] . Conclusions In vitro, curcumin can significantly inhibit proliferation and induce apoptosis of pulmonary fibroblasts of patients with IPF. The mechanism maybe associated with up-regulating expression of Caspase-3.
Objective To explore the clinical features of microscopic polyangiitis ( MPA )complicated with pulmonary involvement in comparison with idiopathic pulmonary fibrosis ( IPF) . Methods Clinical and laboratory data of 27 patients with MPA and 56 patients with IPF in the Drum Tower Hospital from2006 to 2010 were analyzed retrospectively. The differences were compared between the MPA patients with pulmonary fibrosis manifestation ( MPA/PF patients) and those without pulmonary fibrosis manifestation( MPA/NPF patients) , and the IPF patients. Results The differences between the MPA/PF patients and the MPA/NPF patients were rarely found in terms of respiratory symptoms, ANCA positive rate, and multiple organ involvement, but the proportions of suffering severe renal damage and severe pulmonary hypertension in the MPA /PF patients were relatively high ( P lt; 0. 05) . Furthermore, there were significant differences between the MPA/PF patients and the IPF patients in terms of dyspnea, incidence of renal damage, ANCA positive rate, incidence of serious pulmonary hypertension, and multiple organ involvement. The IPF patients were more prone to develop dyspnea while MPA patients were more prone to develop renal damage, high ANCA positive rate, high incidence of serious PAH and multiple organ involvement, such as rush, joint pain,weight loss, fever and gastrointestinal symptoms ( P lt;0. 05) . Conclusions When patients have respiratory symptoms complicated with renal failure, skin damage, fever, and joint pain, the diagnosis of MPA should be considered. For patients who were clinically suspected as interstitial pneumonitis or pulmonary fibrosis,measurement of serumantineutrophil cytoplasmic antibodies and creatinine test are essential for diagnosis.
Objective To investigate the prevalence of obstructive sleep apnea hypopnea syndrome ( OSAHS) in patients with idiopathic pulmonary fibrosis ( IPF) and its clinical significance. Methods Sleep quality and breathing disorders were measured by polysomnography and the relationship with lung function was analyzed in 20 IPF patients. Results Thirteen of 20 subjects ( 65% ) had OSAHS as defined by an AHI ≥5 events per hour. Three subjects ( 15% ) had mild OSAHS ( AHI,5 to 20 events per hour) , and 10 subjects ( 50% ) had moderate-to-severe OSAHS ( AHI≥20 events per hour) . The sleep architecture in these patients showed a reduction in sleep efficiency, rapid eye movement ( REM) sleep and slow wave sleep, and a marked sleep fragmentation due to an increased arousal index. The AHI was negatively correlated with FVC% pred ( r =-0.672, P=0.001) and FEV1% pred ( r =-0.659, P=0.002) , and positively correlated with body mass index ( BMI) ( r=0.791, Plt;0.0001) . Conclusions OSAHS is a common comorbidity in IPF. Early treatment of OSAHS may improve quality of life and the prognosis of patients with IPF.
Objective To explore the prognostic significance of baseline clinical and pulmonary physiological variables on idiopathic pulmonary fibrosis ( IPF) . Methods Patients diagnosed with IPF according to 2011 ATS/ERS/JRS/ALAT statementwere selected from Nanjing DrumTower Hospital between January 1, 2002 and July 31, 2010. The baseline characteristics were abstracted, including age, gender, smoking history, corticosteroid, delay before diagnosis, body mass index, finger clubbing, oxygenation index ( PaO2 /FiO2 ) , C-reaction protein, erythrocyte sedimentation rate ( ESR) , serum lactate dehydrogenase ( LDH) , albumin, vital capacity ( VC) , forced vital capacity ( FVC) , total lung capacity ( TLC) , and singlebreath diffusing capacity of the lung for carbon monoxide ( DLCO) . The relationships between all factors and survival were examined with a univariate Cox proportional-hazard model. Kaplan-Meier method was used to assess the survival probabilities between groups with different baseline characteristics. Results Eighty-four patients were included in this study, with the median survival time of 34. 7 months. PaO2 /FiO2 , FVC% pred, VC% pred, TLC% pred, and DLCO% pred showed significant associations with the mortality of IPF ( hazard ratios 0. 940-0. 994, P lt; 0. 01) . The Kaplan-Meier analyses for above variables also showed significant differences ( P lt;0. 05) . Besides, the statistical difference of survival probability could be found between the patients with elevated serumLDH and those with normal LDH ( 27. 0 months vs. 43. 1 months, P =0. 014) . Conclusions Baseline oxygenation and pulmonary function parameters may indicate the prognosis of IPF patients. Serum LDH may provide clinicians with additional prognostic information.