缬沙坦、普萘洛尔对大鼠门脉高压性结肠病超微结构的影响

The effects of valsartan and propranolol on the colonic ultrastructure in rats with portal hypertensive colopathy

目的观察缬沙坦、普萘洛尔及两者联合应用对门脉高压性结肠病(PHC)大鼠结肠黏膜及黏膜下微循环的影响,并观察其超微结构的变化。方法采用复合因素法制备肝硬化门脉高压(PHT)大鼠模型,将大鼠分为模型组、治疗组(缬沙坦组、普萘洛尔组和联合用药组)、正常对照组。治疗组于第42天模型形成后分别予缬沙坦、普萘洛尔和两药联合灌胃,剂量分别为缬沙坦20 mg/kg,每天1次;普萘洛尔22.5 mg/kg,每天2次;联合组按前述方法同时给药;正常对照组与模型组给予等量自来水灌胃;连续15 d。各组于治疗结束后测门静脉压力(PVP),取结肠组织,光镜下观察、测定黏膜下血管面积及血管扩张量化值,并进行透射电镜观察。结果与模型组比较,各治疗组均有明显降低PVP的作用,差异有统计学意义(P<0.01),并以联合用药组PVP下降最明显。各治疗组结肠黏膜下微静脉面积及微静脉内径量化值均下降(P<0.01),尤以联合用药组作用更为显著。各用药组结肠黏膜上皮吸收细胞微绒毛密集、排列较整齐,断裂少见,普萘洛尔组和联合用药组杯状细胞明显增多,腺上皮细胞线粒体较完整,缬沙坦和联合用药组分泌颗粒较多,尤以联合用药组显著。各治疗组毛细血管内皮细胞内吞饮小泡减少,未见明显肌微丝。结论缬沙坦和普萘洛尔均可减轻大鼠PHC结肠黏膜下血管扩张,改善结肠黏膜血供,对PHC大鼠的结肠黏膜有明显保护作用。

Objective To observe the effects of valsartan and propranolol on the colonic mucosal microcirculation and submucosal ultra-structure changes in rats with portal hypertensive colopathy （PHC）. Methods Portal hypertension（PHT） with cirrhosis was induced by composite factors after 42 days in rats. Rats were divided into a normal control group, a cirrhotic PHT model group, a treatment group with valsartan 20 mg/kg once daily, a treatment group with propranolol 22.5 mg/kg twice daily and a combination treatment group with propranolol and valsartan. The rats were treated for 15 days. The rats in the normal control group and the cirrhotic PHT model group were given water only. At the end of study, portal venous pressures（PVP） were measured. The submucosal vascular areas and metrical diameters of phlebectasia were measured by light microscope. The ultra structure was observed by trans mission electron microscope. Results Compared to the cirrhotic PHT model group, PVPs were significantly decreased in the valsartan, propranolol, and combined groups （P 〈 0. 01）. Vascular areas and metrical diameters of phlebectasia of submucosa were also decreased in three treatment groups（P 〈 0.01）. The colonic mucosal epithelia had less damage in all treatment groups. The goblet cells were increased in propranolol and combined groups. More secretory granule were found in the valsartan and combined groups. Microfilaments were inconspicuous and endothelial phagocytolytic vesicles in capillaries were less in all treatment groups than those in the model group. Conclusions Both valsartan and propranolol can reduce colonic submucosal angiectasis and improve colonic mucosal blood supply in rats with portal hypertension colopathy. They are protective to the colonic mucosa of PHC in rats.