| Portal hypertension due to portal vein blood flow dynamics caused by abnormal changes in a syndrome, its pathophysiology is characterized by increased portal pressure, accompanied by portal venous system of high blood flow, its mechanism is not very clear. Vasoactive substances in the pathogenesis of portal hypertension has been recognized the important role, vasoconstrictor or vasodilator through the regulation of systolic and diastolic systemic or visceral blood vessels, affect the lateral support portal blood flow and intrahepatic or portal circulation lateral branch resistance.Endogenous hydrogen sulfide involved in various physiological and pathological processes, currently the third endogenous gaseous signal molecule hydrogen sulfide that has become a hotspot. According to endogenous hydrogen sulfide in the cardiovascular system and nervous system diseases in the role of research, we hypothesized that portal hypertension in the occurrence, development, progression and prognosis may also play a role. Endogenous hydrogen sulfide in the pathogenesis of portal hypertension is still early stage in the role, so this issue will be of schistosomiasis portal hypertension model for the study, analysis of H2S in the occurrence of portal hypertension, the development of the role of the process to of H2S in the change of portal hypertension and the role of portal hypertension further study the pathogenesis of portal hypertension for the clinical treatment of new ideas or new methods.Objectives1. Explore the human portal hypertension if patients have a change of endogenous hydrogen sulfide. Child to determine classification of portal hypertension in different patients with different levels of H2S explore whether H2S in patients with portal hypertension in the change. 2. Schistosomiasis of the establishment of portal hypertension rabbit disease models, observed morphological changes in different periods of their liver, liver fibrosis, liver function, portal vein diameter, for the smooth implementation of the subject to provide a stable, reliable animal model.3. On the basis of schistosomiasis portal hypertension of rabbit disease models based on the observation of portal hypertension in rabbit the content of plasma H2S changes, as well as the liver function, liver fibrosis relationship between the order of H2S in the pathogenesis of portal hypertension process and its significance.4. The content of H2S of rabbit liver tissue, hydrogen sulfide synthase activity of CSE and CSE mRNA expression in the changes of histological changes in liver fibrosis, in order to further explore the nature of H2S in schistosomiasis portal hypertension in the pathogenesis of effect.5. Define schistosomiasis portal hypertension in rabbits of endogenous hydrogen sulfide H2S on HO-1/CO pathway regulatory role of endogenous hydrogen sulfide and carbon monoxide to clarify the regulation of network and endogenous hydrogen sulfide in the pathogenesis of portal hypertension, to maintain hyperdynamic circulation, such as vascular structure remodeling mechanism.Methods1.Collected in Sep.2007-Dec.2007 at the Huazhong University of Science Tongji Hospital, comprehensive medical ward and the transplant ward hospitalized patients with cirrhosis and portal hypertension clinical data and blood samples. Control group over the same period in healthy people, Tongji Hospital, physical examination. Doppler ultrasound portal vein (PVC), portal hypertension to determine the Child classification, to the determination of plasma protein content of H2S.2. With abdominal penetration treatment of schistosomiasis infection sera produced rabbit model of portal hypertension, infection 8W,12W,16W-line liver MRI, sacrificing blood samples, HE staining, transmission electron microscopy of liver morphology.3. With different concentrations of NaHS standard curve, using the method to the protein content of plasma H2S, by radioimmunoassay of serum HA, C-â…£, LN and PCâ…¢. 4. Detection of H2S content in the liver tissue, liver tissue hydrogen sulfide synthase to RT-PCR detection of CSE mRNA expression in liver tissue 12W select the first line of animal models of HE staining of liver tissue of liver morphology.5. Use molecular biology techniques, immunohistochemistry staining and biochemical detection method to observe the endogenous hydrogen sulfide system on the portal hypertension of schistosomiasis rabbits HO-1/CO pathway.Results1.Child-pugh classification of different patients with portal hypertension H2S levels were significantly different, and with the control group had significant differences. Patients with portal hypertension with H2S content of PVC with a negative linear correlation.2. Rabbit sera 100% success rate of acute infection, the model group in general and the MRI shows reduced liver volume, tissue hardening, uneven liver surface, in the amount of ascites, enlarged spleen. And transmission electron microscopy confirmed that HE existence of liver fibrosis.3. Peripheral blood, portal vein plasma H2S concentration and portal hypertension severity of liver specimens in general, was negatively correlated with liver fibrosis and portal hypertension with aggravated the situation was gradually decreased, to exogenous hydrogen sulfide for body of NaHS, the various indicators improved compared with model group; given after CSE inhibitor PPG, compared with the model of the target group increased.4. PHT rabbit liver tissue content of H2S, hydrogen sulfide oxide synthase activity in liver tissue than in the control group decreased, RT-PCR detection of liver CSE mRNA expression also declined. NaHS can cause portal hypertension in the rabbit liver synthase activity and H2S content increased, the liver pathology prompted portal area of liver fibrosis compared with the same period of model group; by intraperitoneal injection of H2S synthase inhibitor PPG CSE showed portal hypertension rabbit liver disease synthase activity of CSE and the content of H2S decreased, the liver pathology suggest increased hepatic portal area fibrosis.5. PHT group compared with the control group, the plasma content of CO rabbit, liver HO-1 activity, liver HO-1 protein expression, liver HO-1 mRNA expression increased. NaHS+ PHT group decreased compared with those above, and PHT+PPG group and the PHT group, no significant changes.Conclusions1.Portal hypertension in patients with endogenous hydrogen sulfide levels were significantly lower than the normal population, and the severity of the lesions decreased H2S content in plasma, liver and portal vein diameter of Child-pugh grade were negatively correlated, suggesting the body may be reduced H2S the pathogenesis of portal hypertension, the subject provides a theoretical basis for further experimental reliability of the technology.2. This model is a natural evolution of the formation, consistent with human infections caused by schistosomiasis portal hypertension in course of law, and modeling success rate, low mortality, the study of schistosomiasis and portal hypertension an ideal animal model.3. The endogenous hydrogen sulfide in the downturn is likely to prompt the body of portal hypertension and the pathogenesis related to plasma level of H2S in the pathogenesis of portal hypertension may play an appropriate protection.4. That participation of endogenous hydrogen sulfide rabbit liver and portal hypertension progress of fiber, the major decrease in H2S rabbit liver and liver CSE enzyme activity decreased and the reduced expression may be portal hypertension in the pathogenesis play an important role and the maintenance of portal hypertension to a certain extent.5.The endogenous hydrogen sulfide downed HO-1 mRNA and protein expression, reducing HO activity, to reduce the generation of endogenous CO, and then play to reduce vascular resistance in the process of PHT. And ease the progress of liver fibrosis and reduce the role of portal hypertension. Depth study of H2S, NO and CO and mechanism of the relationship between portal hypertension may be the prevention and treatment of new strategies.
|
PDF Full Text Request