- 作者: Francisco J Galvez-Gastelum; Aida A Segura-Flores; Maria D Senties-Gomez; Jose F Munoz-Valle; Juan Armendariz-Borunda
- 作者服務機構: Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, Department of Molecular Biology and Genomics, Guadalajara, Mexico
- 中文摘要: --
- 英文摘要:
Background : Liver fibrosis ranks as the second cause of death in México´s productive-age
population. This pathology is characterized by acummulation of fibrillar proteins
in hepatic parenchyma causing synthetic and metabolic disfunction. Remotion
of excessive fibrous proteins might result in benefit for subjects increasing
survival index. The goal of this work was to find whether the already known
therapeutical effect of human urokinase Plasminogen Activator and human
Matrix Metalloprotease 8 extends survival index in cirrhotic animals.
Methods: Wistar rats (80 g) underwent chronic intoxication with CCl4: mineral oil for 8
weeks. Cirrhotic animals were injected with a combined dose of Ad-delta-huPA
plus Ad-MMP8 (3x1011 and 1.5x1011 vp/Kg, respectively) or with Ad-beta-Gal
(4.5x1011) and were killed after 2, 4, 6, 8 and 10 days. Then, liver and serum
were collected. An additional set of cirrhotic animals injected with combined
gene therapy was also monitored for their probability of survival.
Results: Only the cirrhotic animals treated with therapeutical genes (Ad-delta-huPA+Ad-
MMP-8) showed improvement in liver fibrosis. These results correlated with
hydroxyproline determinations. A significant decrement in alpha-SMA and TGFbeta1
gene expression was also observed. Cirrhotic rats treated with Ad-deltahuPA
plus Ad-MMP8 had a higher probability of survival at 60 days with respect
to Ad-beta-Gal-injected animals.
Conclusion: A single administration of Ad-delta-huPA plus Ad-MMP-8 is efficient to induce
fibrosis regression and increase survival in experimental liver fibrosis. - 中文關鍵字: --
- 英文關鍵字: --