Liposome-mediated gene transfer of endothelial nitric oxide synthase to cirrhotic rat liver decreases intrahepatic vascular resistance
| Autor: | Meng Luo, Zhi-Qi Zhang, Wei Chen, Jiang-feng Qiu, Gang Zhao, Yong-wei Sun, Zhi-Yong Wu, Hua Liu |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Cirrhosis Nitric Oxide Synthase Type III Portal venous pressure medicine.medical_treatment Intraperitoneal injection CCL4 Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Enos Internal medicine medicine Animals Hepatology biology business.industry Gene Transfer Techniques Gastroenterology medicine.disease biology.organism_classification Portal Pressure Rats Disease Models Animal medicine.anatomical_structure Endocrinology Liver chemistry Liposomes Vascular resistance Portal hypertension Vascular Resistance business |
| Zdroj: | Journal of Gastroenterology and Hepatology. 23:e487-e493 |
| ISSN: | 1440-1746 0815-9319 |
| DOI: | 10.1111/j.1440-1746.2007.05244.x |
| Popis: | Background and Aims: Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. The present study evaluates the effects of liposome-mediated gene transfer of eNOS on the intrahepatic vascular resistance and portal venous pressure (PVP) in cirrhotic rats. Methods: Hepatic cirrhosis was induced in male Sprague–Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl4), whereas the control normal rats were given the same dose of peanut oil. Plasmid eukaryotic expression vector (liposome-pcDNA3/eNOS) was injected into the portal vein of CCl4 cirrhotic rats, whereas cirrhotic controls received the same dose of naked plasmid (liposome-pcDNA3) or Tris buffer, and control normal rats received the same dose of Tris buffer. Five days after gene transfer, the levels of eNOS mRNA and protein, NO production, PVP and the changes of hepatic intrahepatic vascular resistance were investigated. Results: Five days after eNOS gene transfer, the levels of eNOS mRNA, eNOS protein and NO production in cirrhotic rats increased remarkably, while hepatic vascular resistance and PVP decreased significantly in cirrhotic rats. Conclusion: Liposome-mediated eNOS gene transfer via intraportal injection is feasible and the increase of intrahepatic eNOS leads to a marked decrease in introhepatic vascular resistance and PVP. These data indicate that intrahepatic eNOS plays an important role in the pathogenesis of portal hypertension and gene transfer of eNOS is a potential and novel therapy for portal hypertension. |
| Databáze: | OpenAIRE |
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