The Protective Effect of Angiotensin Ⅱ AT1Receptor Blocker on Acute Stress-induced Gastric Mucosal Lesions after Intracerebral Hemorrhage in Rats
|Keywords||intracerebral hemorrhage angiotensin Ⅱ AT1 receptor blocker gastricmucosa catecholamines proliferation apoptosis|
ObjectiveTo explore the protective effect of Angiotensin Ⅱ AT1receptor blocker onacute stress-induced gastric mucosal lesions after intracerebral hemorrhage inrats,in order to provide a new target for clinical treatment.MethodsAdult male sprague-dawley rats were randomly divided into thesham-operated group(n=32), the intracerebral hemorrhage group(n=32) and thetreatment group (n=32).Rats were sacrificed at1,2,3and5days after harvestingblood and stomachs.The content of plasma catecholamines were measured byhigh performance liquid chromatography-electrochemical detection. The plasmacatecholamine include plasma epinephrine and plasmanoradrenaline.Observing the general lesions in gastric mucosa and calculatingthe ulcer index. HE staining to observe the morphological changes in the gastricmucosa under light microscope. Immunohistochemistry staining to analysisproliferating cell nuclear antigen protein expression in gastric mucosa.And theterminal-deoxynucleoitidlyl transferase of the mediated nick end labeling toanalysisl apoptotic cells in gastric mucosa.The correlation between plasmacatecholamine and ulcer index,the number of cells stained positive for PCNA,the number of apoptosis stained positive for TUNEL were explored.Results1.The content of plasma catecholamine: compared with the sham-operatedgroup,there were significantly higher content of plasma epinephrine, plasmanoradrenaline in intracerebral hemorrhage group at1d, and the content ofplasma epinephrine increased more significantly.Following time the content ofplasma catecholamine gradually decreased,and reached to minimum at5d, butthey were still significantly higher than the sham-operated group (P <0.01).Andthe content of plasma noradrenaline was no difference between sham-operatedgroup and treatment group at5d. Compared with intracerebral hemorrhagegroup, the content of plasma noradrenaline in the treatment group wasdecreased significantly (P <0.05), and the content of plasma epinephrinedecreased more significantly (P <0.01).2. Generally observe the gastric mucosa and calculate ulcer index: therewere no bleeding point, erosion and ulcer in sham-operated group.There werecongestion and edema in intracerebral hemorrhage group at1d, bleeding pointsformation, and the lesions mainly located in the lesser curvature of the stomach.Lesions were enlarged over the time,emerged erosion,ulcers,the lesions werethe most obvious at3d.In addition, the ulcer index was significantly increasedthan that in sham-operated group(P <0.01).And the leisions started to decreaseat5d,UI decreased,but still larger than that in sham-operated group(P<0.01).Compared with intracerebral hemorrhage group,the degree of gastricmucosa injury,lesion area and the number of lesions were significantly reducedin treatment group(P <0.05).3. HE staining to observe the morphological changes of gastric mucosa bylight microscope:morphological structure of mucosa were intacted, alignedglands, without shedding of epithelial, tissue degeneration and necrosis insham-operated group.Disorganized glands appeared in intracerebral hemorrhage group at1d,and lesions were aggravated over the time,emergingepithelial tissue,glandular necrosis, mucosal shedding, the lesions was themost obvious at3d.In addition,the number of inflammatory cells,the degree ofedema were decreased at5d.Compared with intracerebral hemorrhagegroup,the lesions were significantly reduced in treatment group.4. Immunohistochemistry staining to analysis PCNA expression in gastricmucosa:the expression of PCNA in the gastric pits and glands was examined ineach group.Compared with sham-operated group,the number of PCNA-positivecells was significantly fewer than that in intracerebral hemorrhage group at1d,and reduced over the time.The expression was minimum at3d(P<0.01),and started to increase at5d,but the number of PCNA-positive cells wasstill lower than that in sham-operated group.In addition,the number ofPCNA-positived cells in treatment group was higher than that in intracerebralhemorrhage groups(P <0.05).5. TUNEL staining to analysis apoptosis expression in gastric mucosa:there were few TUNEL-positive apoptosis in sham-operated group. Comparedwith sham-operated group,the number of TUNEL-positive cells was significantlyhigher in intracerebral hemorrhage group at1d, and the expression reached topeak at3d(P <0.01),and started to decrease at5d,but it still higher than that insham-operated group. In addition, the expression of TUNEL-positive apoptosiswas fewer in intracerebral hemorrhage group than that in treatment group at1dand2d (P <0.05), and decreased more fewer at3d and5d (P <0.01).6. Correlation analysis: The content of plasma epinephrine and plasanoradrenaline were positively correlated with ulcer index, the number ofTUNEL-positive apoptosis (P <0.01) in gastric mucosa.However they werenegatively correlated with the number of PCNA-positive cells in gastric mucosa(P <0.01). Conclusions1. The high content of plasma epinephrine, plasma noradrenaline canreduce the number of PCNA-positive cells and increase the number ofTUNEL-positive apoptosis in gastric mucosa in rast with intracerebralhemorrhage.2. Angiotensin Ⅱ AT1receptor blocker can decrease the content of plasmaepinephrine, and plasma noradrenaline.And as a result, the mumber ofPCNA-positive cells in gastric mucosa increased, the number ofTUNEL-positive apoptosis decreased.3. Angiotensin Ⅱ AT1receptor blocker play an important therapeuticeffects related pathogenesis in acute stress-induced gastric mucosa lesions inrats with intracerebral hemorrhage.