缬沙坦、普萘洛尔对大鼠门静脉高压性胃病胃窦黏膜下微循环及其超微结构的影响

Effect of valsartan,propranolol on microcirculation and ultramicrostructure of gastric mucosa in rats with portal hypertension gastropathy

目的探讨缬沙坦(valsartan,Val)、普萘洛尔(propranolol,Pro)单独以及两者联合用药对大鼠门静脉高压性胃病(por-tal hypertension gastropathy,PHG)的保护作用。方法 90只大鼠随机分为5组。缬沙坦组,给予缬沙坦20 mg/kg,1次/d,灌胃;普萘洛尔组,给予普萘洛尔22.5 mg/kg,2次/d,灌胃;缬沙坦+普萘洛尔组(联合用药组)按相同方法同时给药;正常对照组与模型组给予等量自来水,灌胃,连续15 d。各组均测定血清透明质酸(hyaluronic acid,HA)、Ⅲ型前胶原(precollagenⅢ,PCⅢ)。取胃窦组织,行光镜下观察并测定黏膜下血管面积和最大直径。同时取胃窦组织进行透射电镜观察。结果与模型组比较,缬沙坦组和联合用药组血清中HA、PCⅢ含量均降低(P<0.05)。缬沙坦、普萘洛尔和联合用药均可使PHG大鼠黏膜下层血管面积、最大直径减小(P<0.01),尤以联合用药作用更为显著(P<0.01)。光镜下模型组黏膜下微静脉扩张、迂曲、管壁变薄,淋巴细胞浸润,各用药组较模型组黏膜下血管扩张扭曲好转,微血管及血窦扩张轻,尤以联合用药组更显著。透射电镜下各用药组仅见上皮细胞之间间隙增宽,毛细血管扩张较模型组轻,细胞线粒体较完整,分泌颗粒较多,微绒毛排列整齐,较模型组细胞、线粒体等破坏明显减轻,尤以联合用药组显著。结论缬沙坦和普萘洛尔均可减轻PHG大鼠胃窦黏膜下血管扩张,改善黏膜血供,对PHG大鼠的胃黏膜有明显保护作用,尤以联合用药作用更为显著。同时缬沙坦有减轻肝纤维化作用。

Objective To investigate the protective effect of valsartan,propranolol and their combination on portal hypertension gastropathy（PHG） in rats.Methods Ninety rats were randomly divided into 5 groups.The rats were gavaged with valsartan 20 mg/kg once a day in valsartan group,and propranolol 22.5 mg/kg twice a day in propranolol group.The rats were simultaneously given valsartan and propranolol in valsartan＋propranolol group by gavage.The rats were given the equal doses of tap water once a day by gavage in normal group and model group.The administration lasted for 15 d.The serum hyaluronic acid（HA） and precollagenⅢ（PCⅢ） were measured.The pyloric antrum was obtained to detect the submucosal vessel areas and its biggest diameter under light microscope and observe the ultramicrostructure under transmission electron microscope.Results Compared with model group,the serum contents of HA and PC Ⅲ decreased in valsartan group and valsartan＋propranolol group（P〈0.05）,and submucosal vessel areas and biggest diameter of submucosa also decreased in valsartan group,propranolol group and valsartan ＋ propranolol group,especially in valsartan＋propranolol group（P〈0.01）.In model group,phlebectasia,varices,tubal wall thinning and leukomonocyte infiltration were observed under light microscope,while phlebectasia and varices were significantly improved in medication groups,especially in combination group.The widened interspace and angiotelectasis were observed under transmission electron microscope in medication groups,but angiotelectasis was slighter than that in model group.Compared with model group,the damages of cell and chondriosome were improved in medication groups,especially in combination group.Conclusion Both valsartan and propranolol,especially their combination have significant protective effect on gastric mucosa of PHG in rats by lessening submucous angiotelectasis of antrum and improving the blood supply of mucosa.And valsartan can also lessen the liver fibrosis.