Published online Nov 28, 2013. doi: 10.3748/wjg.v19.i44.7992
Revised: October 18, 2013
Accepted: October 19, 2013
Published online: November 28, 2013
Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension.
Core tip: Triple partial portal vein ligation in the rat induces in the long term (22 mo) both splanchnic alterations, i.e., liver steatosis and portal hypertensive intestinal vasculopathy associated with a portal hypertensive microbiome, and systemic alterations, i.e., a wound-like inflammatory aortic response. These alterations support this experimental model of prehepatic portal hypertension for studying the pathophysiological mechanisms involved in the low-grade inflammatory response produced.