The Relationship Between Bleeding And Hemodynamic Changes And Expression Of INOS/NF-kB In Splenic Vein Wall In Patients With Portal Hypertension

Background & ObjectivePortal hypertension (PHT) is a common clinical syndrome characterized by a pathological increase in portal pressure. It is often present in patients with chronic liver diseases. In PHT, high blood pressure and high blood flow constitute a special hemodynamic state in the portal venous system. Stress (the force of unit area) can be induced by pressure and flow. With further study of PHT, people found that hemodynamic disorders appear in patients with PHT, but also the existence of portal venous system vascular lesions, known as Portal hypertension vasculopathy (PHV).And it plays an important role in the development of PHT. Domestic and international studies have demonstrated that the pathogenesis of portal hypertension include" backward flow theory" and the "forward flow theory". Forward flow theory deem that it is no difference between portal collateral vascular resistance with portal hypertension and normal resistance of portal vein, and portal vein congestion by large inflows of portal vein portal vein contribute to the maintenance of portal hypertension.Hemorrhage of esophagus and stomach is one of the most serious complications of portal hypertension. There are not only portal vein system and systemic hemodynamic disorders in portal hypertension, but also metabolic disorders of a variety of vasoactive substances, which may promote or affect an important factor in bleeding. There are debates about the diameter and blood flow volume and velocity of flow of portal vein and splenic vein in portal hypertension. Whether there is relationship between them and bleeding is little research. Excessive production of NO may be one of the main cause of hemangiectasis and the weakening of vasoconstriction in portal hypertension. Inducible nitric oxide synthase (iNOS) is an important enzyme responsible for NO production. Excessive production of NO may be a consequence of iNOS overexpression. There are much more researchs about the relationship between NF-κB and iNOS in other field, but less reaseachs in expression of iNOS/NF-κB in splenic vein wall in patients with portal hypertension and Whether there is relationship between them and bleeding needs further research.MethodsVarious branches of the portal vein system of PHT group were measured before operation. Splenic veins from patients with PHT (n=48, PHT group) were removed during pericardial vascular devascularization with splenectomy, while normal splenic veins were from splenic rupture (n=10, control group). According to bleeding, pationts in PHT group were divived into 2 groups, patients in group A were without history and those in group B bled over once. Samples from splenic veins were examined by HE staining. All of them were observed under optic microscopes. The expression of iNOS and NF-κB proteins in the splenic veins of patients with PHT and normal control were analysed with immunohistochemistry. Pearson correlation analysis was used to evaluate the relationship between the expression of iNOS and NF-κB in patients with PHTResults1. The Dpv were 14.87±0.44 mm in group A and 14.69±0.44 mm in group B. There was no significant differences in Dpv between two groups. The Vpv were 11.43±0.52 cm/s in group A and 9.98±0.55 cm/s in group B. Vpv was much higher in group A than in group B. Qpv were 1190.41±60.46 L/ min in group A and 1013.21±52.29 L/ min. Qpv was much higher in group A than in group B 2. The Vsv were 9.99±0.52 cm/s in group A and 9.74±0.65 cm/s in group B.There were no significant differences in Average velocity of splenic vein in between two groups. The Dsv were 10.23±0.34 mm in group A and 10.74±0.41 mm in group B. Dsv was less in group A than in group B. The Qsv were 492.52±20.76 L/min in group A and 528.26±34.22 L/ min in group B. Qsv was lower in group A than in group B.3. The ratio of Qsv to Qpv were 0.42±0.03 in group A and 0.52±0.03 in group B. There was significant lower in group A than in group B (p<0.05)4. Immunohistochemical staining:The positive signal for iNOSwere observed in the cytoplasm. The iNOS expression in endothelial cells and smooth muscle cells in splenic vein of patients with PHT showed positive or strongly positive signal, In the control group, staining was negative or weakly positive. The mean optical density value of the positive area was significantly higher in group B than that in group A the control group.5. NF-κB immunohistochemical staining product was localized mainly in the cytoplasm and nuclei of endothelial cells. The NF-κB expression in endothelial cells in splenic vein of patients with PHT showed positive or strongly positive signal, In the control group, staining was negative or weakly positive. The mean optical density value of the positive area was significantly higher in group B than that in group A the control group.6. Pearson correlation analysis showed that the expression of iNOS protein in splenic vein of patients with PHT two groups were positively correlated with NF-κB protein (r=0.969, P< 0.01).Conclusions1. The levels of Vpv and Qpv are obviously decreased in the patients bled with portal hypertension. This shows that bleeding and hemodynamic changes in portal vein are relevance.2. Qsv was significantly increased in PHT group,and this indicates that spleen and portal hypertension hyperdynamic circulation. The ratio of Qsv to Qpv was significant increased in patients bled, this shows that Qsv and bleeding are relevance 3. The expression of iNOS and NF-κB in the splenic vein of patients with PHT are higher than those in control group, and the higher in patients bled. It showes that iNOS and NF-κB may be relevant with bleeding.4. There is a positive correlation between the expression of iNOSand NF-κB protein. They may show a collaborative interaction effect.