Objective To investigate the effect of zileuton, leukotrienes inhibitor, on pulmonary fibrosis induced by bleomycin(BLM) in the rats. Methods Fifty-four adult male Sprague-Dawley rats were divided randomly into three groups: BLM group (M group), control group (C group) and leukotriene inhibitor group(S group). Each group contained eighteen mice. S group was treated with zileuton everyday at a dose of 100 mg/kg after a single intratracheal instillation of BLM at a dose of 5 mg/kg; M group was treated with saline instead of zileuton after instillation of bleomyein;C group was treated with saline instead of zileuton and BLM. Six rats in each group were killed on 7,14 and 28 days after instillation. The rat lungs were harvested for HE and Masson trichrome stain, hydroxyproline content was determined, immunohistochemistry was used to detect the expressions of α-SMA and TGF-β1 in the lung tissues. Results The hydroxyproline content of M group was significantly higher than that of S group, the degree of alveolitis in S group was ameliorated as compared with that in M group(P<0.05);a significantly reduced fibrosis was observed in S group compared with that in M group. The expression of TGF-β1 and α-SMA in lung tissue of S group was significantly lower than that of M group. Conclusions Leukotriene inhibitor could reduce the degree of bleomycin-induced pulmonary fibrosis in rats. It may inhibite the proliferation of fibroblasts by inhibiting the expresson of TGF-β1 in lung tissue.
Key words:
Leukotrienes inhibitor; Pulmonary fibrosis; Bleomycin
To evaluate the significance of changes in the serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients with multiple organ dysfunction syndrome (MODS) regarding its diagnosis and judgement of severity and outcome, and to investigate the correlations between the levels of tumor necrosis factor-alpha (TNF-alpha), sFas and sFasL.Enzyme linked immunoadsorbent assay (ELISA) was used in the determination of serum sFas, sFasL and TNF-alpha in 36 patients with MODS. Thirty-two non SIRS patients and 20 healthy individuals comprised the control groups. The acute physiology and chronic health evaluation III (APACHE III) scoring system and modified MODS scoring system were used to assess patients' clinical severity. The differences of sFas and sFasL levels between MODS group and control groups and between survival and dead patients were observed. The correlations between sFas, sFasL and TNF-alpha levels and severity of MODS and the correlations between the TNF-alpha levels and the levels of sFas and sFasL were also observed.The serum levels of sFas, sFasL and TNF-alpha in patients with MODS were significantly higher than those in controls (P<0.05 or P<0.01), and were associated with severity of the disease (all P<0.01) . The sFas and sFasL levels were found to be significantly higher in the patients who eventually died as compared to those in the patients who survived (both P<0.05). Positive correlations were noted between the TNF-alpha levels and the levels of sFas and sFasL(both P<0.01). The serum levels of sFas and sFasL were elevated with the increase of the number of failure organs in MODS patients.The serum levels of sFas and sFasL may serve as diagnostic and prognostic indicators for MODS. TNF-alpha may help enhance the expression of Fas/FasL system.
Objective To observe the effect of Valsartan on a rat model of acute lung injury and the expression of transforming growth factor-β,TGF-β) ,Smad2/3, Smad7. Methods Twenty-four male adult Sprague-Dawley rats were random divided into three groups : The bleomycin (BLM) group, the control group, and the Valsartan group. Each group contained eight rats. The Valsartan group was treated with Valsartan everyday at a dose of 20 mg/kg after a single intratracheal instillation of bleomycin at a dose of 5mg/kg. BLM group was treated with saline instead of Valsartan after an instillation of bleomycin. The control group was treated with saline instead of Valsartan and bleomycin. Each group was killed at the 7th day after instillation. The lung tissues were harvested for H. E. stain, the immunohistochemistry was used to detect the expressions of TGF-β1, Smad2/3 ,and Smad7. Results The degree of alveolitis in the Valsartan group was ameliorated, compared with those in BLM group (P <0. 01). The expressions of TGF-β1 and Smad2/3 in lung tissue of the Valsartan group were significantly lower than that of BLM group(P <0. 01). The expressions of Smad7 in lung tissue of the Valsartan group were significantly higher than that of BLM group (0.23 ±0. 02 vs0. 36 ±0.03, P <0.01). Conclusions Valsartan could alleviate acute lung injury in rats, which probably be due to the expression decrease of TGF-β1 and Smad2/3 and the expression increase of Smad7 in lung tissues.
Key words:
Valine/AA/PD; Respiratory distress syndrome,adult/ME; Transforming growth factor beta/BI; Smad proteins/BI; Lung/IN/ME