Parreira Natállia Alle, Ramalho Fernando Silva, Augusto Marlei Josiele, Silva Deisy Mara, Prado Cibele Maria, Elias Júnior Jorge, Rodrigues Vanderlei, Ramalho Leandra Náira Zambelli
Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Exp Parasitol. 2018 Aug;191:9-18. doi: 10.1016/j.exppara.2018.05.004. Epub 2018 Jun 8.
Schistosomiasis mansoni is involved in hepatic fibrogenesis and portal hypertension. Previous studies proved that blockade of some components of the renin-angiotensin system (RAS) reduce liver fibrogenesis. However, the effects of inhibition of early stages of RAS pathway in schistosomal fibrosis have not been studied yet. Thus, the aim of this study was to compare the role of different antihypertensive drugs on hepatic fibrosis in murine schistosomiasis. BALB/c mice (n = 50) weighing 20g were subjected to inoculation of 50 cercariae and submitted to different treatments: aliskiren, 50 mg/kg (n = 10); bradykinin, 2 μg/kg (n = 5); losartan, 10 mg/kg (n = 10); lisinopril 10 mg/kg (n = 5) and control, proportional volume vehicle (n = 5); daily for 14 weeks. Six animals were not subjected to cercariae inoculation or any type of treatment. Ultrasound, histological, immunohistochemical and proteomic analyzes were performed to evaluate markers associated with hepatic fibrogenesis. The hepatic areas stained with Sirius red and thenumber of cells marked by α-SMA in animals treated with aliskiren, bradykinin, lisinopril and losartan were diminished when compared to control group, demonstrating reduced hepatic fibrosis after RAS blockade. These results were reinforced by ultrasonography analysis and protein expression of TGFβ. These findings demonstrated the effect of RAS inhibition on hepatic fibrosis in murine schistosomiasis, with the most evident results being observed in the losartan and aliskiren treated groups. The main mechanisms underlying this process appear to involve anti-fibrogenic activity through the inhibition of collagen and TGFβ synthesis.
曼氏血吸虫病与肝纤维化和门静脉高压有关。先前的研究证明，阻断肾素-血管紧张素系统（RAS）的某些成分可减少肝纤维化。然而，RAS途径早期抑制在血吸虫性肝纤维化中的作用尚未得到研究。因此，本研究的目的是比较不同抗高血压药物对小鼠血吸虫病肝纤维化的作用。将体重20g的BALB/c小鼠（n = 50）接种50条尾蚴，并进行不同处理：阿利吉仑，50mg/kg（n = 10）；缓激肽，2μg/kg（n = 5）；氯沙坦，10mg/kg（n = 10）；赖诺普利10mg/kg（n = 5）以及对照组，给予等体积溶媒（n = 5）；每日给药，持续14周。6只动物未接种尾蚴或接受任何类型的处理。进行超声、组织学、免疫组化和蛋白质组学分析以评估与肝纤维化相关的标志物。与对照组相比，用阿利吉仑、缓激肽、赖诺普利和氯沙坦处理的动物中，天狼星红染色的肝面积和α-SMA标记的细胞数量减少，表明RAS阻断后肝纤维化减轻。超声分析和TGFβ蛋白表达进一步证实了这些结果。这些发现证明了RAS抑制对小鼠血吸虫病肝纤维化的作用，在氯沙坦和阿利吉仑治疗组中观察到的结果最为明显。这一过程的主要机制似乎涉及通过抑制胶原蛋白和TGFβ合成的抗纤维化活性。
