Xu Y Y, Shen F J, Wu L L
Gastroenterology Department, The First Hospital of Shanxi Medical University, Taiyuan 030001, China.
Zhonghua Gan Zang Bing Za Zhi. 2019 Sep 20;27(9):677-680. doi: 10.3760/cma.j.issn.1007-3418.2019.09.004.
To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril. Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL(4)) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman's correlation analysis. In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) μg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) μg/ml, < 0.05]. After benazepril treatment, NOX4 mRNA expression and ROS concentration were decreased than the model group [(15.93 ± 5.01), (0.78 ± 0.44) μg/ml vs. (31.78 ± 3.96), (1.82 ± 0.46) μg /ml, < 0.05], while Nrf2 mRNA expression was higher than the model group [(6.69 ± 4.86) vs. (4.01 ± 3.40), < 0.05]. There was a positive correlation between Nrf2 and NOX4, Nrf2 and ROS, and NOX4 and ROS ( = 0.616, 0.411, 0.802, < 0.05). Benazepril may exert an anti-hepatic fibrosis effect by activating Nrf2 expression, or may inhibit the ROS-mediated oxidative stress in response to NOX4.
研究贝那普利对肝纤维化大鼠核因子E2相关因子2（Nrf2）、烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（NOX4）表达及活性氧（ROS）浓度的影响，探讨贝那普利可能的抗纤维化机制。将22只健康雄性Sprague-Dawley大鼠随机分为3组：对照组（6只）、模型组（8只）和贝那普利治疗组（8只）。模型组和贝那普利治疗组在建模和治疗过程中有2只大鼠死亡，建立了四氯化碳（CCL₄）诱导的肝纤维化模型。贝那普利组大鼠经胃管饲给予贝那普利8周。采用常规苏木精-伊红和Masson染色法对各组肝组织损伤进行评估。采用RT-PCR检测肝组织中Nrf2、NOX4的mRNA水平，采用比色法测定血清ROS浓度。所有数据均以均数±标准差表示，采用SPSS21.0统计软件进行分析。数据采用单因素方差分析进行比较，两组间两两比较采用LSD-t法。采用Spearman相关分析进行相关性分析。模型组肝脏中，随着肝纤维化加重，Nrf2mRNA、NOX4 mRNA表达及ROS浓度均高于对照组[（4.01±3.40）、（31.78±3.96）、（1.82±0.46）μg/ml vs.（0.12±0.11）、（2.03±0.31）、（1.56±0.84）μg/ml，P<0.05]。贝那普利治疗后，NOX4 mRNA表达及ROS浓度较模型组降低[（15.93±5.01）、（0.78±0.44）μg/ml vs.（31.78±3.96）、（1.82±0.46）μg/ml，P<0.05]，而Nrf2 mRNA表达高于模型组[（6.69±4.86）vs.（4.01±3.40），P<0.05]。Nrf2与NOX4、Nrf2与ROS、NOX4与ROS之间均呈正相关（r=0.616、0.411、0.802，P<0.05）。贝那普利可能通过激活Nrf2表达发挥抗肝纤维化作用，或抑制由NOX4介导的ROS氧化应激反应。
