[Influence of pyrrolidine dithiocarbamate (PDTC) on expression of transforming growth factor beta(1), matrix metalloproteinase-2 and tissue inhibitor-1 of metalloproteinase in rats with pulmonary damage induced by paraquat].
OBJECTIVE
To investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ).


METHODS
Fifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope.


RESULTS
The TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01).


CONCLUSIONS
PDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.
Shao
Chun-Feng
CF
School of Public Health, Fudan University, Shanghai 200032, China.
Chang
Xiu-Li
XL
Wu
Qiang-En
QE
Ban
Ting-Ting
TT
Jiang
Nan
N
Yao
Xin-Min
XM
Zhou
Zhi-Jun
ZJ
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D010269:Paraquat / Q000506:poisoning*; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C020972:pyrrolidine dithiocarbamic acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D010269:Paraquat