Calcium ; metabolism ; Growth Substances ; metabolism ; Humans ; Pulmonary Fibrosis ; drug therapy ; metabolism ; prevention & control ; Taurine ; therapeutic use

To ascertain whether connective tissue growth factor (CTGF) participates in the remodeling of pulmonary artery at the early-stage of bleomycin (BLM)-induced pulmonary fibrosis, mean pulmonary arterial pressure, the expression of type I and type III collagens, and the expression and location of CTGF in pulmonary artery and arteriole were investigated in the present study. Sprague-Dawley rats received instillation of BLM [5 mg/kg body weight, in 0.5 mL of normal saline (NS)] or instillation of the same amount of NS as control. Mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery. Type I and type III collagens were examined with Sirius red staining under polarized light. CTGF expression was investigated by using immunohistochemistry, and was represented as average optical density and percentage of positive area of CTGF. The mean pulmonary arterial pressure was higher in rats on day 14 after BLM instillation [(19.5+/-2.9) mmHg] than that in the control rats [(14.8+/-1.2) mmHg] (P<0.05). The type I and type III collagens were increased both in pulmonary artery and arteriole of rats on day 14 after BLM instillation, compared with those in the control rats (P<0.05, P<0.01, respectively). The ratio of type I/III collagens in pulmonary artery was also higher in BLM-treated rats than that in the control rats (P<0.05). The values of average optical density of positive CTGF staining were increased both in pulmonary artery (0.37+/-0.02) and arteriole (0.40+/-0.03) of rats on day 14 after BLM instillation, compared with those in the control rats (artery, 0.34+/-0.01; arteriole, 0.29+/-0.01) (both P<0.05). The percentages of positive area of CTGF were higher in pulmonary artery (8.40+/-1.13) and arteriole (12.4+/-2.0) of rats on day 14 after BLM instillation than those in the control rats (artery: 1.42+/-0.63; arteriole: 1.16+/-0.34), respectively (both P<0.05). The increased positive CTGF staining areas were mainly located in the endothelium and smooth muscle layer. It is therefore concluded that CTGF expression increases in the endothelium and smooth muscle layer of pulmonary artery and arterioles during high pulmonary arterial pressure and remodeling of pulmonary artery at the early-stage of BLM-induced pulmonary fibrosis, and that the increased CTGF might be one of the mechanisms of maintenance and development of pulmonary hypertension.
Animals ; Bleomycin ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Connective Tissue Growth Factor ; metabolism ; Hypertension, Pulmonary ; Pulmonary Artery ; metabolism ; Pulmonary Fibrosis ; metabolism ; Rats ; Rats, Sprague-Dawley

Humans ; Pulmonary Fibrosis ; metabolism ; pathology ; Signal Transduction ; physiology ; Transforming Growth Factor beta1 ; metabolism ; Wound Healing ; physiology

Animals ; Cytokines ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Pulmonary Fibrosis ; metabolism ; pathology ; Reactive Nitrogen Species ; metabolism ; Reactive Oxygen Species ; metabolism

OBJECTIVETo study the impact of pulmonary fibrosis on erectile function in rats and its mechanism.

METHODSForty 12-week-old healthy male SD rats were randomly divided into Groups A (4-week pulmonary fibrosis), B (6-week pulmonary fibrosis), C (4-week control, and D (6-week control). The models of pulmonary fibrosis were established by injection of bleomycin at 5 mg/kg in the trachea, while the controls were injected with normal saline only. At 4 and 6 weeks, all the rats were subjected to determination of the serum testosterone (T) level, arterial blood gas analysis, measurement of intracavernous pressure/mean arterial pressure (ICP/MAP), and examination of NOS activity and cGMP content. The mRNA expressions of eNOS, iNOS and nNOS in the corpus cavernosum penis were detected by real-time PCR, and that of eNOS analyzed by Western blot.

RESULTSThe 3 V and 5 V of the ICP/mapx100 in Group C were 16.37 +/- 2.19 and 27.19 +/- 3.18, significantly lower than 30.78 +/- 2.66 and 50.09 +/- 6.97 in Group A (P < 0.05); those in Group D were 10.17 +/- 1.31 and 17.40 +/- 1.74, significantly lower than 31.45 +/- 3.07 and 51.23 +/- 7.23 in Group B (P < 0.05), and so were they in Group D than in C (P < 0.05). PaO2 was significantly lower in Group C than in A ([75.50 +/- 13.87] mmHg vs [103.80 +/- 6.88] mmHg, P < 0.05) , and so was it in Group D than in B ( [83.60 +/- 5.50] mmHg vs [102.70 +/- 5.77] mmHg, P < 0.05). Group C showed a significantly increased serum T level as compared with A ([391.1 +/- 264.7] ng/dl vs [175.9 +/- 53.0] ng/dl, P < 0.05), so did Group D ([745.4 +/- 408.8] ng/dl) versus Group B ([177.8 +/- 52.3] ng/dl) and C (P < 0.05). NOS activity and cGMP content in the corpus cavernosum significantly decreased in Group C ([1.50 +/- 0.14] U/mg prot and [35.69 +/- 3.64] pmol/mg) compared with A ([2.66 +/- 0.39] U/mg prot and [51.10 +/- 7.22] pmol/mg) (P < 0.05), so did they in D ([1.40 +/- 0.20] U/mg prot and [34.55 +/- 4.30] pmol/mg) versus B ([2.75 +/- 0.36] U/mg prot and [52.15 +/- 6.86] pmol/mg) (P < 0.05), but neither showed any significant difference between Groups D and C (P > 0.05). The expression of the eNOS protein was significantly lower in Group C than in A (0.79 +/- 0.01 vs 0.87 +/- 0.01, P < 0.05), so was it in D than in B and C (0.71 +/- 0.02 vs 0.88 +/- 0.01 and 0.79 +/- 0.01, P < 0.05). The expression of eNOS mRNA was significantly higher in Group C than in A (4.46 +/- 0.92 vs 2.61 +/- 0.68, P < 0.05), but did not show any significant difference between D and B (2.79 +/- 0.60 vs 2.69 +/- 0.65, P > 0.05), nor did the expressions of nNOS mRNA and iNOS mRNA between the pulmonary fibrosis groups and the controls (P > 0.05).

CONCLUSIONPulmonary fibrosis may induce erectile dysfunction by suppressing the expression of the eNOS protein and reducing NOS activity and cGMP content in the corpus cavernosum penis of rats.

Animals ; Erectile Dysfunction ; etiology ; metabolism ; Male ; Nitric Oxide Synthase ; metabolism ; Penis ; metabolism ; Pulmonary Fibrosis ; complications ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDBleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.

METHODSBleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.

RESULTSSimvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.

CONCLUSIONSSimvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

Animals ; Antibiotics, Antineoplastic ; Bleomycin ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Simvastatin ; pharmacology

Humans ; Interleukin-18 ; chemistry ; metabolism ; Pulmonary Fibrosis ; etiology ; pathology ; Silicosis ; complications ; pathology ; physiopathology

Biomarkers ; Humans ; Idiopathic Pulmonary Fibrosis/genetics* ; MicroRNAs/metabolism* ; Sjogren's Syndrome/genetics*

Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can destroy the structure and function of cells through the damage of biological macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can regulate the proliferation, differentiation and apoptosis of cells through several signaling pathways and participate in fibrogenesis of many organs including hepatic and pulmonary fibrosis. Recent study shows that ROS might have an important effect on the forming of myelofibrosis. Consequently, ROS plays a significant role in the fibrogenesis of tissues and organs. In this review, the relevance between ROS and common tissues and organs fibrosis is summarized.
Animals ; Bone Marrow ; pathology ; Bone Marrow Diseases ; metabolism ; pathology ; Fibrosis ; Humans ; Liver ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; Lung ; pathology ; Pulmonary Fibrosis ; metabolism ; pathology ; Reactive Oxygen Species

OBJECTIVETo study whether co-stimulatory molecule CD40 of alveolar macrophage (AM) participated in the occurrence and development of silicosis, and to explore the intervention of Yiqi Huoxue Decoction (YHD) in the fibrosis of silicosis patients.

METHODSTotally 46 silicosis inpatients and outpatients were recruited and randomly assigned to the Western treatment group (A) and the Chinese medicine (CM) treatment group (B), 23 in each group. Patients in Group A received routine symptomatic treatment such as anti-inflammation, phlegm resolving, anti-spasm, and asthma relief, and so on. Patients in Group B additionally took YHD, one dose daily for 14 successive days. Besides, another 18 patients with chronic cough and sense of laryngeal foreign bodies were recruited as the normal control group, who had no obvious lesion confirmed by bronchofi6roscope and clinical diagnosis of the lung. They were treated by symptomatic supporting treatment. The alveolar lavage fluid was collected from all patients and isolated, and AM cells were cultured. The level of CD40 mRNA was detected by RT-PCR. The expression of CD40 protein was detected by Western blot.

RESULTSCompared with the normal control group, expression levels of CD40 mRNA and CD40 protein significantly increased in Group A (P < 0.01). Compared with Group A, expression levels of CD40 mRNA and CD40 protein significantly decreased in Group B (P < 0.01).

CONCLUSIONSHighly expressed co-stimulatory molecule CD40 of AM might participate in pulmonary fibrosis. YHD could hinder its roles, inhibit the progression of fibrosis, thereby playing an interventional role of treatment.

CD40 Antigens ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Fibrosis ; Humans ; Lung ; Male ; Pulmonary Fibrosis ; RNA, Messenger ; metabolism ; Silicosis ; drug therapy ; metabolism