ABSTRACT
Objective: This study evaluated the ability of heme oxygenase-1 to prevent or reverse renal fibrosis. Methods: Sprague-dawley male rats were submitted to unilateral ureteral obstruction and divided into groups: non-treated and hemin. Biochemical and histological analyses were performed. We also conducted RT-PCR to verify the expression of heme oxygenase-1, MCP-1, IL1-beta, IL-6, TNF-alfa, COL-I, COL-III, PAI-1 and fibronectin mRNA. Results: heme oxygenase-1 expression significantly increased in treated animals. The non treated group showed significantly higher levels of proteinuria than the Hemin group. The protein/urinary creatinine ratio in obstructed pelvis was also higher in non treated group, which also showed greater albuminuria and higher percentage of fibrosis when compared to the Hemin group. The expression of pro-inflammatory and pro-fibrotic molecules was significantly higher in the non treated group. Conclusions: The treatment induced the expression of heme oxygenase-1, preventing the installation of fibrosis and even limiting its progression.
Objetivo: Este estudo avaliou a capacidade da heme oxigenase-1 em prevenir ou reverter o quadro de fibrose renal. Métodos: Ratos Sprague-dawley machos foram submetidos a UUO e divididos nos grupos: não-tratados e Hemin. Avaliou-se a função renal, fez-se análise histológica e realizou-se RT-PCR para verificar expressão de heme oxigenase-1, MCP-1, IL1-beta, IL-6, TNF-alfa, COL-I, COL-III, PAI-1 e Fibronectina. Resultados: Houve expressão significativamente maior de heme oxigenase-1 nos animais tratados. O grupo não tratado apresentou níveis significativamente maiores de proteinúria em relação ao grupo Hemin. O índice proteína/creatinina urinária da pelve obstruída também foi maior no grupo não tratado, que apresentou ainda maior albuminúria e maior porcentagem de fibrose em relação ao grupo Hemin. A expressão de moléculas pró-inflamatórias e pró-fibróticas foi significativamente maior no grupo não tratado. Conclusões: O tratamento induziu a expressão de heme oxigenase-1, evitando a instalação da fibrose e mesmo limitando sua progressão.
ABSTRACT
Objective To observe pulmonary fibrosis in severe acute respiratory syndrome (SARS) and to discuss the mechanisms of pulmonary fibrosis in SARS. Methods Hematoxylin and Eosin staining (H&E), histology staining and immuno-histochemical staining (SP methods) were used to investigate the lungs from 4 autopsy cases. Antibodies against collagen type Ⅲ, ?-smooth muscle actin(?-SMA), Fas, FasL and transforming growth factor ?1(TGF-?1) were used for immunohistochemical studies. Results All these four lung tissues showed different degree of pulmonary fibrosis, including the organization of exudative fibrin, glomerulus-like fibrosis in alveolar spaces, the thickening of the alveolar septum, proliferation of fibroblasts, the hyperplasia of collagen fibers and the consolidation of lungs. Sirius red staining and collagen type Ⅲ staining showed the type Ⅲ and the type Ⅰ collagen fibers were the main components of the hyperplastic collagen fibers. ?-SMA were expressed in fibroblasts, immunoreactivity to Fas, FasL, TGF-?1 were all positive and located in plasma of pneumocytes, macrophages and lymphocytes. Conclusions The pulmonary fibrosis can be observed early in SARS patients and the pathogenesis may be involved in the co-effect of many effective cells, inflammatory mediators and cytokines.