Objective To systematically evaluate the effectiveness of N-acetylcysteine (NAC) combined with low-dose glucocorticoid for patients with idiopathic pulmonary fibrosis (IPF). Methods Such databases as The Cochrane Library (Issue 12, 2012), EMbase (January 1974 to July 2012), PubMed (January 1966 to July 2012), CHEST (January 1995 to July 2012), CNKI (January 1994 to July 2012), CBM (January 1978 to July 2012), VIP (January 1989 to July 2012) and WanFang Data (January 1995 to July 2012) were searched to collect the randomized controlled trials (RCTs) about NAC combined with low-dose glucocorticoid versus glucocorticoid alone for IPF patients. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality, and then the meta-analysis was performed using RevMan 5.1 software. Results A total of seven RCTs including 264 IPF patients were included. The results of meta-analysis demonstrated that, compared with the glucocorticoid used alone, a) NAC combined with low-dose glucocorticoid could significantly improve PaO2 (SMD=0.82 mmHg, 95%CI 0.30 to 1.35, P=0.002) and DLco (SMD=0.59 mmHg, 95%CI 0.16 to 1.03, P=0.008) with a significant difference. b) NAC combined with low-dose glucocorticoid could significantly improve all clinical symptoms (RR=1.56, 95%CI 1.26 to 1.92, Plt;0.000 1). Conclusion NAC combined with low-dose glucocorticoid for IPF patients can significantly improve PaO2, DLco, and the clinical symptoms such as cough, difficulty breathing after activities, cyanosis, and Velcro rales. Due to the quantity and quality limitation of included studies, this conclusion still needs to be further proved by more high quality and double blind RCTs.
ObjectiveTo investigate the effect of indocyanogen green retention rate (ICGR) measurement and Child-Pugh classification of liver function in the preoperative evaluation of hepatic functional reservation. MethodsThe level of ICGR at 15 min (ICGR15) and the percentage of liver fibrosis in 103 patients with liver cancer were measured before hepatectomy, and the Child-Pugh classification of liver function was evaluated before and after the operations, and their connections were analyzed. ResultsAs the rise of Child-Pugh classification of liver function, the percentage of liver fibrosis increased gradually, there were significant differences between any two Child-Pugh classification (Plt;0.05). There was a linear correlation between the ICGR15 and the liver fibrosis percentage (rs=0.960, Plt;0.05). The value of preoperative ICGR15 in patients with postoperative Child-Pugh classification from grade A to grade B or grade B to grade C was gnificantly higher than that in patients with stabilization of Child-Pugh classification before and after operations (Plt;0.05). ConclusionICGR15 combined with Child-Pugh classification can improve the accuracy for the evaluation of preoperative hepatic functional reservation.
Immunohistochemical study on 39 specimens of hepatobilibary duct stricture due to stones were performed. Collagen types Ⅲ and Ⅳ were studied by quantitative analysis. The results showed that significant increase of type Ⅲ collagen was found in the stenotic bile duct wall, the portal area and liver sinusoid with fibrosis. Abnormal increasing of type Ⅳ collagen was found in the liver sinusoid of the stenotic bile duct.
Objective To explore the effects of SU5416，a vascular endothelial growth factor receptor (VEGFR) inhibitor，on inflammation in mice with bleomycin-induced pulmonary fibrosis.Methods C57BL/6 mice were randomly divided into four groups，ie.a control group，a bleomycin-induced pulmonary fibrosis (BPF) group,early intervention with SU5416 group (days 1-14，SE)，and delayed intervention with SU5416group (days 15-28，SD).Bleomycin (10 mg/kg) was instilled into the trachea of the mice to induce pulmonary fibrosis.After the instillation，SU5416 (50 mg/kg) was injected into the peritoneal cavities of the mice twice a week.The mice treated with bleomycin alone or with bleomycin followed by SU5416 were sacrificed on the day 14 and day 28 after the instillation of bleomycin.Lung tissues were taken and processed for determination of hydroxyl proline content.Bronchoalveolar lavage fluid (BALF) was collected for total and differential cell counts and measurements of lactic dehydrogenase (LDH) levels.Results It was found that the hydroxyl proline contents，the number of macrophages，and the LDH contents from the mice treated with bleomycin alone on day 14 were greatly increased.However，only the hydroxyl proline showed a significant increase in the mice treated with bleomycin alone on day 28.The number of macrophages，LDH contents，and hydroxyl proline contents were greatly reduced in the mice treated with bleomycin and early administration of SU5416 on day 14 when compared with those treated with bleomycin alone.But there were no significant differences in the above parameters of the mice treated with bleomycin and delayed administration of SU5416 on day 14.Conclusion This study indicates that early intervention by SU5416 might attenuate the fibrosis through inhibiting early inflammation in animal model of pulmonary fibrosis induced by bleomycin.
Objective To investigate the effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in rats with pulmonary fibrosis，and explore the mechanism of sodium ferulate on pulmonary fibrosis.Methods A rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin (5 mg/kg).Thirty SD rats were randomly divided into three groups (n=10 in each group)，ie.a control group，a pulmonary fibrosis model group，and a sodium ferulate group.The lung histopathology and the expression of collagen was examined by HE staining and collagen fibril staining respectively.The expressions of TGF-βRII and Smad4 mRNA in the lung tissue were detected by situ hybridization.And the expression of TGF-β1 mRNA was detected by real-time fluorescence-quantification RT-PCR.Results Collagen fibril staining indicated that the expression of pulmonary collagen in the model group was significantly higher than that in the control group and sodium ferulate group (Plt;0.001).The mRNA expressions of pulmonary TGF-β1，TGF-βRII and Smad4 were significantly higher in the model group than those in the control group (all Plt;0.01)，and were significantly lower in the sodium ferulate group than those in the model group (all Plt;0.05).Conclusions Sodium ferulate can effectively reduce pulmonary fibrosis through inhibition of the mRNA expression of TGF-β1，TGF-βRII and Smad4 in the lung tissue，thus influence the TGF-β1/Smad4 signal transduction way and inhibit the target gene activation.
Objective To investigate the role of IFN-γ in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods Seventy-five SD rats were randomly divided into five groups (15 rats in each group)，ie.a normal group，a bleomycin-induced pulmonary fibrosis model group，a dexamethasone-treated group，a high-dose IFN-γ-treated group (150 000 U/kg) and a low-dose IFN-γ-treated group (50 000 U/kg).Five rats in each group were randomly killed in 7th day，14th day and 28th day after relative treatment respectively，and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical method were adapted to determine protein levels of TGF-β1，CTGF，type Ⅰcollagen and type Ⅲ collagen in pulmonary tissues.Results Histopathological study showed that treatment with either dexamethasone or IFN-γ (both high dose and low dose) remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis (compared with model group，all Plt;0.05).Histoimmunochemical study suggested that both dexamethasone and IFN-γ could inhibit the expression of TGF-β1，CTGF，type Ⅰand type Ⅲ collagen (compared with model group，all Plt;0.05)，and the suppression of TGF-β1，type Ⅰand type Ⅲ collagen expression was more obvious in high-dose IFN-γ-treated group than those in low-dose group (Plt;0.05).Conclusions INF-γ possesses apparent anti-fibrosis effect that is similar to dexamethasone but with less side effect.Such effect may resulted from reduced production of type Ⅰand type Ⅲ collagen through expression inhibition of cytokines such as TGF-β1 and CTGF.
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 explore whether epithelial to mesenchymal transition ( EMT) occurs in bleomycin( BLM) induced pulmonary fibrosis, and the involvement of bronchial epithelial cells( BECs) in the EMT. Methods BLM-induced peribronchial fibrosis in an α-smooth muscle actin-Cre transgenic mouse( α-SMACre /R26R) was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. Results BLMtreated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some alveolar epithelial cells( AECs) in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by α-SMA immunostaining. Conclusions EMT occurs in BLM-induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.
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..
美国胸科协会(ATS)和欧洲呼吸学会(ERS)联合发表的共识中，将特发性肺纤维化(IPF)定义为原因不明并以普通型间质性肺炎(UIP)为特征性病理改变的一种慢性纤维化性间质性肺疾病。在2000年ATS／ERS的IPF共识意见 及2003年中华医学会呼吸病学分会IPF的诊断和治疗指南(草案) 中均推荐的治疗方案为糖皮质激素，或与细胞毒制剂(环磷酰胺及硫唑嘌呤)联合使用。但目前尚缺乏循证医学证据支持该治疗方案能够提高IPF患者生活质量或生存率 。近年来随着对IPF的发病机制认识的深入，越来越多的临床医师和研究者对IPF患者是否需要用糖皮质激素等药物的治疗提出了质疑。