Effects Of EGCG On Pulmonary Fibrosis Induced By Bleomycin And Its Molecular Mechanisms In Rats

Objective：To investigate the molecular mechanisms of epigallocatechin gallate （EGCG）on Bleomycin-induce pulmonary fibrosis in rats.Methods：Sprague-Dawley rats were randomly divided into control, model, prednisonegroup and EGCG large-dose, middle-dose, small-dose group. Pulmonary fibrosis modelwas established by intratracheal injection of bleomycin (5mg/kg). Then the rats weretreated with corresponding dose of EGCG by intragastric administration. After28days,Animals were sacrificed to observe the state of the overall behavior of rats, body weight,serum total antioxidant capacity (T-AOC), total superoxide dismutase(T-SOD) levels;tissue hydroxyproline (HYP) content, total antioxidant capacity (T-AOC) and totalsuperoxide dismutase(T-SOD) levels. The extent of pulmonary alveolitis and fibrosis wereevaluated by histopathological and biochemical analysis. tumor necrosis factor-α(TNF-α)and interleukin6(IL-6) in bronchoalveolar lavage fluid (BALF) were detected by ELISA.the level of α-SMA,COL-Ⅰ,TGF-β1,Smad2and Smad7mRNA were assayed bysemi-quantitative RT-PCR. The expression of α-SMA,COL-Ⅰ,TGF-β1,Smad2and Smad7protein in lung tissue were analyzed by western blot. the level of miR-21were assayedby Realtime-PCR.Results：Compared with control group, the intragastric administration of EGCG couldincrease body weight of rats (P<0.05). EGCG reduced the extent of alveolitis, fibrosis(P<0.05,P<0.01);Biochemical indicators showed that:EGCG dramatically decreased thecontent of HYP in the lung tissue(P<0.01). EGCG could increase T-AOC and T-SOD levelsin serum; enhance T-AOC and T-SOD levels in tissue (P<0.05, P<0.01); ELISA resultsshowed that: EGCG reduced the contents of TNF-α and IL-6（P<0.05）in BALF. PCR and Western blot results showed that: EGCG decreased the level of α-SMA,COL-Ⅰ,TGF-β1,Smad2mRNA（P<0.05, P<0.01）,but the expression of Smad7mRNAin lungtissue of rats were significantly increased (P<0.05). EGCG inhibited the increases in theprotein expressions ofα-SMA,COL-Ⅰ,TGF-β1and Smad2（P<0.05,P<0.01）, and thedecreases in the protein expression of Smad7(P<0.05,P<0.01). the expression of miR-21in lung tissue of rats were significantly decreased（P<0.01）.Conclusion：EGCG could alleviated bleomycin-induced pulmonary fibrosis in rats, whichmight be related with its anti-inflammatory effects, anti-oxidation,down regulate theexpression of miR-21.inhibition of TGF-β singnal pathway, and reducing of collagenproduction.