[Effect of hydrogen sulfide on Bleomycin-induced pulmonary fibrosis in rats].
OBJECTIVE
To explore the change of endogenous hydrogen sulfide and the effect of exogenously applied H(2)S on Bleomycin-induced pulmonary fibrosis in rats.


METHODS
(1) Forty-eight male Wistar rats were randomly divided into control group, fibrosis group, fibrosis+NaHS-low group (1.4 micromol/kg, bid intraperitoneally) and fibrosis+NaHS-high group (7.0 micromol/kg, bid intraperitoneally). Pulmonary fibrosis was induced by intratracheal instillation of bleomycin. The control group and pulmonary fibrosis group were injected with the same volume of normal saline. Pulmonary pathology changes were observed, the plasma H(2)S concentration,the activity of CSE in lung tissue and the contents of MDA, hydroxyproline were detected on the 7th and 28th days respectively after bleomycin administration. CSE mRNA was also measured using quantitative RT-PCR. (2) Isolated lung tissues were exposed to Fe(2+)/H(2)O(2) without or with different concentrations of NaHS (10(-5), 5 x 10(-5), 10(-4), 10(-3) mmol/L) at 37 degree Celsius for 10 minutes, and the MDA content was assayed by biochemical method.


RESULTS
(1) Compared with rats in control group, the concentration of plasma H(2)S and the activity of CSE in lung tissues in fibrosis group decreased on day 7 (all P<0.01); On the 28th day, the level of plasma H(2)S increased clearly (P<0.01) and the activity of CSE was ascendant without significant difference compared with that of control group. Relative CSE mRNA amounts in lung tissues increased 34%, 144%, respectively (all P<0.01) in rats of fibrosis group compared with those of control group. The contents of MDA and hydroxyproline increased significantly in fibrosis group compared with those of control group on days 7, 28 (all P<0.01). In NaHS-low group and NaHS-high group, the contents of MDA and hydroxyproline decreased markedly (all P<0.01). (2) The contents of MDA in incubation of lung tissues at different concentrations of NaHS were all decreased as compared with those in incubation with Fe(2+)/H(2)O(2) alone (all P<0.01). When NaHS was at 10(-4) mol/L, the MDA content reversed to the lowest value, which had the highest value at 10(-3) mol/L of NaHS.


CONCLUSIONS
Endogenous CSE/H(2)S pathway was involved in the pathogenesis of rat pulmonary fibrosis. Exogenously applied H(2)S could attenuate the process of pulmonary fibrosis possibly because of reducing oxidative stress.
Li
Hong
H
Department of Gerotology, Peking University First Hospital, Beijing 100034, China.
Liu
Xin-min
XM
Geng
Bin
B
Pan
Chun-shui
CS
Qi
Yong-fen
YF
Wu
Sheng-ying
SY
Tang
Chao-shu
CS
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D011651:Pulmonary Artery / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000378:metabolism
D013440:Sulfides; D001761:Bleomycin; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide