[Therapeutic effects and mechanism of saikosaponin-d in mice with bleomycin-induced pulmonary fibrosis].
OBJECTIVE
To study the therapeutic effects and mechanism of saikosaponin-d (SSd) in mice with bleomycin (BLM)-induced pulmonary fibrosis.


METHODS
According to the random number table, 180 mice were randomly divided into 5 groups. Four groups were pulmonary fibrosis models. Fibrosis model mice were established by intratracheal injection of bleomycin (5 mgxkg(-1)). They were BLM, DXM, SSd and SSd + DXM groups (n = 40 each). At 1 hour post-modeling, DXM, SSd and SSd + DXM groups were injected ip with dexamethasone (DXM, 5 mgxkg(-1)xd(-1), 0.1 ml), SSd (1.8 mgxkg(-1)xd(-1), 0.18 ml), DXM + SSd (0.28 ml) respectively qd until Day 28. BLM group was similarly dosed with normal saline. In addition, a normal control group (NC group, n = 20) treated likewise. The mice were anesthetized and sacrificed at Days 3, 7, 14, 28 for harvests of serum and lung tissue samples. The conventional histopathological changes of lung tissue were observed. Except for NC group, modeling groups of mice were used to observe the natural survival rate. Such indices as superoxide dismutase (SOD) and malonaldehyde (MDA) were examined both in lung tissue and serum samples. And hydroxyproline (HYP) was tested only in lung tissue.


RESULTS
SSd could markedly increase the survival rate (80.0% in SSd and SSd + DXM groups vs 50.0% in BLM group, P < 0.05) and reduce alveolitis and fibrosis in mice. In comparison with BLM group, the levels of HYP of three treatment groups (DXM, SSd and SSd + DXM) in lung tissue was significantly lower (P < 0.05) at Days 14 and 28. The levels of MDA both in serum and lung tissue were significantly lower at Days 3, 7 and 14 (P < 0.05). The serum level of SOD was significantly higher at Days 3, 7 and 14 while the level of SOD in lung tissue was significantly higher at Days 3 and 7 (P < 0.05, P < 0.01).


CONCLUSIONS
SSd has marked therapeutic effects upon bleomycin-induced pulmonary fibrosis in mice. And the mechanism may be associated with its anti-lipid peroxidation effect.
Zheng
Jin-xu
JX
Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China. jxuzh135@163.com
Lu
Kun-qin
KQ
Xia
De-gang
DG
Tian
Gao-run
GR
Huang
Zhen-jie
ZJ
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D005260:Female; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008517:Phytotherapy; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012503:Saponins / Q000627:therapeutic use*
D012503:Saponins; D001761:Bleomycin; D009828:Oleanolic Acid; C025759:saikosaponin D