Experiment Study On The Treatment With Valsarta N Plus Propranolol In Rats With Cirrhotic Portal Hypertensive Colopathy

Objective To observe the effects of valsartan,propranolol and the two drugs combination on the change of the NOS expression in colonic mucosa membrane and submucosa and the level of the tumor necrosis factor and nitrogen monoxidum in blood serum in rats with portal hypertensive colopathy(PHC),and further to explore the therapeutic action and mechanism of these two drugs combination in rats with portal hypertensive colopathy(PHC).Methods:Portal hypertension (PHT) with cirrhosis was induced by composite factors after8weeks in60majority male Sprague-dawley rats, another15as normal control group. During the course of model rats’formation,11rats had dead. Eight weeks later, portal vein pressure(PVP), mean arterial pressure(MAP) and heart rate(HR) were measured in5of49cirrhosis rats and5of normal control group, hepatic tissue and colonic tissue was observed with light microscope. It was confirmed that PHT was successfully formed. Than model rats were randomly divided into model group and experimental group including valsartan group, propranolol group and two drugs combined group. And each group had11rats. In2weeks,experimental groups were respectively administered valsartan,propranolol and valsartan plus propranolol. The dosage of valsartan was20mg/kg, once a day, that of propranolol being15mg/kg, twice everyday. Valsartan plus propranolol group was administered the same dosage by gavage. Normal control group and model group were given the equal dose of tap water at the same time. The administration of each group continued2weeks. Each group was measured PVP, MAP and HR. The metabolin of nitrogen monoxidum and the tumor necrosis factor in blood serum was detected. Colonic tissue was observed with light microscope to measured the microvessel area in mucous membrane and submucosa and the nitricoxide synthase was observed by immunohistochemical staining and then analyzed by image analysis system. Other colonic tissue was observed by transmission electron microscope.Results:①Results of MAP,PVP and HR:PVP of model group was significantly higher than control group (P＜0.01). Compared with model group,experimental groups significantly decreased PVP respectively (p＜0.01). The combined group more significantly reduced PVP than valsartan and propranolol group. And the difference was not significant between valsartan and propranolol group. Compared with the combined group, the other two groups had a significant difference(p＜0.05), but the difference was not significant among themselves(P＞0.05). But there had no difference of MAP among these groups. Compared with model group, the combined group and propranolol both decreased HR,but the difference was not significant(p>0.05).②Results of light microscope Under the light microscope, model group was observed with the incresasing number of capillary and venule,also angiotelectasis and phlebectasia of colonic mucous membrane and colonic submucous, with a lot of lammatory cells infilrtation.The area of capillary and venule of model group was significantly higher than other groups (P<0.01).The area of the two being cut down in experimental groups significantly,especially for the combined group.③By transmission electron microscope:The normal control group observed with epithelial integrited, and endoplasmic reticulum in the mucosal epithelialis cells enriching the goblet cells. The model group observed with microvilli of absorptivecells and goblet cells were fewer and shorter or abruption. Mitochondrions of epithelialis cells intumesced, goblet cells were fewer, cells gap were explanded. Every experimental group could present with microvilli of absorptivecells and epithlialis cells lining up densely, orderly and less abruptly, mitochondrions of epithelialis cells intumesced were improved, and shown increase of goblet cells.④esults of immunohistochemistry The positive cells of iNOS and eNOS was mainly located in the cytoplasm, and distributed in the vascular endothelial cells. Compared to nomal control group the expression of iNOS and eNOS in submucosal vascular endothelial cells in model group was significantly stronger(p＜0.01). The expression of the two in all experimental groups decreased after treatment. The difference between combination group and model group was significantly(p<0.01). ⑤Results of the level of the metabolin of nitrogen monoxidum in blood serum:Compared to normal control group, the level of nitrogen monoxidum in model group was significantly higher(p＜0.01). The level of nitrogen monoxidum in all experimental groups decreased after treatment, and the combination group decreased significantly(p＜0.01). But there had no difference between valsartan and propranolol group(p＞0.05).⑥Results of the level of the tumor necrosis factor in blood serum: Compared to normal control group, the level of TNF-α in model group was significantly higher(p＜0.01). The level of TNF-α in all experimental groups decreased after treatment, and the combination group decreased significantly(p＜0.01). But there had no difference between valsartan and propranolol group(p＞0.05).Conclusion:Valsartan and propranolol both can reduce the level of TNF-a in scrum, decrease the expression of NOS in colonic mucosa membrane and submucosa and the synthesis of nitrogen monoxidum in rats with cirrhotic portal hypertensive colopathy, which can moderates damage of colon in PHC rats. Their combination can strengthen the efficacy, and have little influence on systemic hemodynamics.