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[Effects of andrographolide on the concentration of cytokines in BALF and the expressions of type I and III collagen mRNA in lung tissue in bleomycin-induced rat pulmonary fibrosis].

AIM
To investigate the effects of andrographolide on the concentration of TNF-α and TGF-β1 in bronchoalveolar lavage fluid (BALF) and the expressions of type I and III collagen mRNA in Lung tissue in bleomycin (BLM)-induced pulmonary fibrosis in rats.


METHODS
90 healthy SD male rats were randomly divided into 6 groups with 15 rats each group: normal saline (NS) group, BLM group, prednisone (Pred) group and different doses of andrographolide groups (andrographolide group A 62.5 mg/kg, andrographolide group B 125 mg/kg and andrographolide group C 250 mg/kg). BLM was given to BLM group, Pred group and andrographolide group A, B, C by intratracheal instillation, and same volume of NS was given to NS group in the same way. And then NS was given to NS group and BLM group, Pred was given to Pred group and different does of andrographolide were given to andrograoholide group A, B, C by gavage every day. Five rats of each group were killed respectively at day 7, 14, 28 after intratracheal instillation. Alveolitis and fibrosis were observed by HE and Masson staining. Real-time fluorescent quantitative reverse transcription- polymerase chain reaction (FQ RT-PCR) was performed to detect the expressions of type I and III collagen mRNA in lung tissue, and the concentration of TNF-α and TGF-β1 in BALF was determined by enzyme-linked immunosorbnent assay. Blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also examined.


RESULTS
(1) The AST, ALT, BUN and Cr in every group had no significant diference(P>0.05). (2) Alveolar septal edema, inflammatory cell infiltration and fibrosis were not found in NS group. In the BLM group, lots of inflammatory cells infiltration were observed in the alveolar at day 7; the alveolitis was still existed, but inflammatory cells were significantly reduced, and the number of the fibroblasts and matrix in alveolar septum were obviously increased at day 14, at the same time, alveolar structure was damaged and alveolar septum widened; the inflammation cells infiltration of the alveolar was relieved, pulmonary fibrosis was increased, and parts of alveolar space was disappeared , severe fibrosis was found at day 28. It was similar between andrographolide group A and BLM group in pathomorphology. A lot of inflammatory cells infiltration and local accumulation were observed at day 7 in andrographolide group B, C and Pred group. However, compared with andrographolide group A and BLM group, the fibrosis at day 14, 28 was significantly reduced.(3) The concentration of TGF-β1, TNF-α in BALF of NS group was significantly lower than that of Pred group, BLM group, andrographolide group A, B, C at each time point(P<0.05). The concentration of TGF-β1 and TNF-α in BALF of BLM group at day 7, 14, 28 was higher than that of Pred group, andrographolide group B and andrographolide group C (P<0.05). Compared with BLM group, the concentration of TGF-β1 and TNF-α in BALF of andrographolide group A had no significant difference. (4) The expression of type I and III collagen mRNA in lung tissue of NS group was significantly lower than that of group Pred, BLM, andrographolide group A, B, C at each time point (P<0.05). The expression of type I and III collagen mRNA in lung tissue of BLM group at day 7, 14, 28 was higher than that of Pred group, andrographolide group B and andrographolide group C (P<0.05). Compared with BLM group, the expression of type I and III collagen mRNA in lung tissue of andrographolide group A had no significant difference.


CONCLUSION
In BLM-induced rat pulmonary fibrosis, andrographolide could attenuate alveolitis and fibrosis, decrease mRNA expression of collagen I and III in lung tissue and decrease the concentration of TNF-α and TGF-β1 in BALF. It had no side effects on liver and kidney function.