Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis via modulating angiotensin-converting enzyme 2/ angiotensin-(1-7) axis in rats.
Pulmonary fibrosis (PF) is a common complication in those interstitial lung diseases patients, which will result in poor prognosis and short survival. Traditional therapeutic methods such as glucocorticoid and cytotoxic drugs are insufficient for treating PF and may cause severe side effects. Recent studies showed that traditional Chinese herbal abstraction such as Tanshinone IIA (TIIA) was displayed significant anti-PF effects in animal models. However, the exact mechanisms underlying the protective effects of TIIA were not fully understood. Here we further investigated the protective effects of TIIA and its mechanisms underlying. PF models of rat were induced by bleomycin (BLM); TIIA was administered subsequently. The PF changes were identified by histopathological analyses. The results showed that BLM resulted in severe PF and alveolar inflammation; together with significant elevation of transforming growth factor-β 1 (TGF-β1). Angiotensin-converting enzyme 2 (ACE-2) together with angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. TIIA treatment notably attenuated BLM induced PF and inflammation, decreased expression of TGF-β1 and reversed ACE-2 and ANG-(1-7) production in rat lungs. Thus we may draw the conclusion that TIIA may exert protective effects on BLM induced PF in rats, and the ACE-2/ANG-(1-7) axis may ascribe to those protective effects.
1. Department of Pediatrics of Xijing Hospital, Fourth Military Medical University; ; 3. Lung Injury and Repair Center, Fourth Military Medical University;
Huajie
H
Wu
4. Medical Examination Center of Beijing Military General Hospital;
Yan
Y
Li
2. Department of Pathophysiology, Fourth Military Medical University; ; 3. Lung Injury and Repair Center, Fourth Military Medical University;
Yanxia
Y
Wang
2. Department of Pathophysiology, Fourth Military Medical University;
Dunquan
D
Xu
5. Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University.
Congcong
C
Li
2. Department of Pathophysiology, Fourth Military Medical University;
Manling
M
Liu
1. Department of Pediatrics of Xijing Hospital, Fourth Military Medical University;
Xin
X
Sun
2. Department of Pathophysiology, Fourth Military Medical University; ; 3. Lung Injury and Repair Center, Fourth Military Medical University;
Zhichao
Z
Li
D045784:Abietanes / Q000008:administration & dosage*; D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism
D045784:Abietanes; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C021751:tanshinone; D001761:Bleomycin; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
ANG-(1-7).; Pulmonary fibrosis; Tanshinone IIA; angiotensin-converting enzyme 2; transforming growth factor beta