Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Pharmacology Department, Medical Division, National Research Centre, Giza, Egypt.
J Tissue Eng Regen Med. 2019 Dec;13(12):2131-2141. doi: 10.1002/term.2940. Epub 2019 Oct 22.
The renin-angiotensin system (RAS) has a substantial role in liver fibrosis, cirrhosis, and portal hypertension. Hence, targeting RAS through angiotensin-converting enzyme (ACE) inhibitors can mend hepatic fibrosis; the current study was designed to examine the potential fibrosis inhibition activity of perindopril using a rat model of liver fibrosis induced by thioacetamide (TAA). Four groups of rats were used throughout this study, Group I (control group); rats received the vehicle. TAA was used for inducing liver fibrosis in rats by intraperitoneal injection of 200-mg/kg body weight twice a week for 6 weeks. Group II served as (TAA group). Rats of Groups III and IV were given perindopril at doses of 2 and 8 mg/kg 2 weeks after TAA administration and continued concomitantly with TAA till the end of the experiment. Injection of TAA resulted in a significant increase in aminotransferases' activities and bilirubin with a significant decrease in serum albumin and total protein and a significant decrease in hepatic content of GSH and SOD. Additionally, TAA injection raised the hepatic content of TGF-β1, α-SMA, TNF-α, and level of MDA. Histological and immunohistochemical data presented marked fibrosis in liver sections of TAA-administrated rats with increased collagen deposition, elevated METAVIR scoring, and increased expression of α-SMA, caspase-3, and AT1R. Oral dosing of perindopril for 4 weeks concomitant with TAA could mend the altered parameters near to normal values and abolished the ongoing fibrosis extension. In conclusion, these results demonstrated that perindopril, as ACE inhibitor, could grant a superior remedial nominee in preventing liver fibrosis progression through targeting angiotensin II formation.
肾素-血管紧张素系统（RAS）在肝纤维化、肝硬化和门脉高压中起着重要作用。因此，通过血管紧张素转换酶（ACE）抑制剂靶向 RAS 可以修复肝纤维化；本研究旨在使用四氯化碳（TAA）诱导的肝纤维化大鼠模型来研究培哚普利的潜在抗纤维化活性。本研究共使用了四组大鼠，第 I 组（对照组）；大鼠接受载体。TAA 通过每周两次腹腔注射 200mg/kg 体重的方式用于诱导大鼠肝纤维化，共进行 6 周。第 II 组作为（TAA 组）。TAA 给药 2 周后，第 III 组和第 IV 组大鼠分别给予培哚普利 2 和 8mg/kg，并与 TAA 同时给药直至实验结束。TAA 注射导致氨基转移酶活性和胆红素显著升高，血清白蛋白和总蛋白显著降低，肝内 GSH 和 SOD 含量显著降低。此外，TAA 注射增加了 TGF-β1、α-SMA、TNF-α 和 MDA 的肝含量。肝组织学和免疫组织化学数据显示，TAA 给药大鼠的肝组织有明显的纤维化，胶原沉积增加，METAVIR 评分升高，α-SMA、caspase-3 和 AT1R 的表达增加。TAA 给药同时给予培哚普利 4 周可使改变的参数接近正常值，并消除正在进行的纤维化扩展。总之，这些结果表明，作为 ACE 抑制剂的培哚普利可以通过靶向血管紧张素 II 的形成，为预防肝纤维化进展提供更好的治疗候选物。
