Dursun Hakan, Albayrak Fatih, Uyanik Abdullah, Keleş Nuri Osman, Beyzagül Polat, Bayram Ednan, Halici Zekai, Altunkaynak Zuhal Berrin, Süleyman Halis, Okçu Nihat, Ünal Bünyamin
Department of Gastroenterology, Atatürk University, School of Medicine, Erzurum.
Turk J Gastroenterol. 2010 Dec;21(4):387-95. doi: 10.4318/tjg.2010.0125.
BACKGROUND/AIMS: Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats.
In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined.
The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 μm3, respectively. Significant differences were found between values of all groups (p<0.01, Mann-Whitney U test). According to histopathological investigation, Group 3 and particularly Group 4 showed some microscopic abnormalities such as dilatation in sinusoids central veins and branches of portal vein, irregularities of the hepatocyte columns, significant mononuclear cell infiltrations, and unstained vacuoles in the cytoplasm of the hepatocytes. Histological structure was protected from the destructive effects of ovariectomy and hypertension in Groups 5 and 6.
Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.
背景/目的:钙通道阻滞剂越来越多地用于治疗高血压。绝经和高血压都是肝损伤及其他几种循环系统异常的重要危险因素。本研究的目的是确定氨氯地平和拉西地平在大鼠卵巢切除诱导的绝经后模型和醋酸脱氧皮质酮-盐诱导的高血压模型中的作用。
在本研究中,动物被分为以下六组:对照组(第1组)、高血压组(第2组)、卵巢切除组(第3组)、卵巢切除合并高血压组(第4组)、卵巢切除、高血压并接受氨氯地平治疗组(第5组)以及卵巢切除、高血压并接受拉西地平治疗组(第6组)。实验结束时,取出肝脏并对组织样本进行组织学和体视学检查。
各组肝细胞的数值密度分别为0.000422、0.00329、0.000272、0.00259、0.00374和0.000346μm³。所有组的值之间均存在显著差异(p<0.01,曼-惠特尼U检验)。根据组织病理学研究,第3组尤其是第4组显示出一些微观异常,如中央静脉和门静脉分支的窦状隙扩张、肝细胞柱不规则、显著的单核细胞浸润以及肝细胞胞质中的无色空泡。第5组和第6组的组织学结构免受卵巢切除和高血压的破坏作用。
我们的实验结果表明,高血压和绝经后时期均对肝细胞数量和肝脏组织学结构有负面影响。氨氯地平和拉西地平似乎都能改善高血压和/或绝经后时期相关的肝细胞数量减少。因此,我们认为拉西地平尤其是氨氯地平对肝脏具有重要的保护和恢复作用。