Therapeutic effect of ulinastatin on pulmonary fibrosis via downregulation of TGF­ß1, TNF­α and NF­κB.

Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis. The results demonstrated that ulinastatin had the ability to ameliorate interstitial fibrosis and alveolar exudates and to protect against lung diseases induced by smoke, irradiation or silica particles. The mechanism of ulinastatin resulted in the downregulation of inflammatory cascades: Transforming growth factor­ß1, tumor necrosis factor­α and nuclear factor­κB, as demonstrated by western blotting and ELISA. Ulinastatin treatment with a high dose (100,000 U/kg body weight/day) resulted in an attenuated inflammatory response, and inhibited fibrosis formation in lungs, suggesting that ulinastatin may become a part of a clinical therapeutic strategy.

[The anti-fibrotic effects of Qidan granule in experimental silicosis].

OBJECTIVE: To investigate the anti-fibrotic effects of Qidan granule in rats. METHODS: The rats were randomly divided into six experimental groups: normal group, model group, Qidan group, Tetrandrine group. All rats except normal group were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. Qidan group and Tetrandrine group were treated with Qidan granule (3125 mg/kg) or treated with Tetrandrine (22 mg/kg) respectively. All the rats were sacrificed after 5 months. Calculate Lung/body coefficient by weighting the lung wet weight and the body weight of rats. Content of Hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 was examined by using enzyme-linked immunosorbent assay (ELISA). Paraffin embedded lung sections with HE staining, VG staining and Gomori staining were observed under light microscope. RESULTS: In Qidan group and Tetrandrine group, Lung/body coefficient and content of Hydroxyproline and expression of transforming growth factor-beta1 were lower as compared with model group (P < 0.05). Model group mainly showed III approximately IV grade silicotic nodule, which contained thick collagen and sparse reticulum fibe; Qidan group and Tetrandrine group appeared with II grade silicotic nodule, which contained tiny collagen and intensive reticulum fibe. Tetrandrine group showed injury of kidney, and others were normal. CONCLUSION: Qidan granule extract should prevent and from inhibit the remarkably silicotic fibrosis in rats.

[Experimental study on effect of Qidan granule in treatment of pulmonary fibrosis in rats].

OBJECTIVE: To investigate the therapeutic effect and mechanism of Qidan granule on blemycinA5-induced pulmonary fibrosis in rats. METHODS: A total of 70 SD rats were randomly divided into normal group, the model group, Qidan group and hydrocortisone group and observed for 28 days and 42 days, respectively. Rat pulmonary fibrosis was induced by intrabronchial injection of blemycinA5. Treatment started from day 14 to day 42 with Qidan granule and Hydrocortisone for 14 days (day 28 group) and for 28 days (day 42 group), respectively. The lung pathological grades were observed by hematoxylin and eosin (HE) staining and expressions of transforming growth factor beta (TGF-beta(1)) protein and tumor necrosis factor alpha (TNF-alpha) protein were tested by the immunohistochemical technique. RESULTS: (1) Lung pathobiology fibrosis were alleviated was alleviated significantly in Qidan granule group compared with those in model group and hydrocortisone group (p < 0.01). (2) In Qidan group and hydrocortisone group, the expression of TGF-beta(1) protein was 1.71 +/- 0.17 and 1, 78 +/- 0.17 in day 28 group and day 42 group, respectively. The expression of TNF-aprotein was 2.16 +/- 0.40 and 1.98 +/- 0.33 in day 28 group and day 42 group, respectively. The expression of TGF-beta(1) and TNF-alpha protein was significantly difference from those in the model group and the hydrocortisone group (p < 0.01). CONCLUSIONS: Qidan granule ameliorate the pulmonary fibrosis by decreasing expressions of TGF-beta(1) and TNF-alpha proteins in lung tissue.