Departamento de Farmacología, Laboratorio de Hepatología Experimental, Centro de Investigación y de estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Ciudad de México, México.
Toxicol Mech Methods. 2024 Jan;34(1):13-19. doi: 10.1080/15376516.2023.2244061. Epub 2023 Aug 29.
The severity of fibrosis is central to the therapeutic course for patients with chronic liver disease; therefore, early detection of liver fibrosis is critical for timely therapeutic interventions. Liver biopsy is the gold standard for the diagnosis of liver fibrosis; however, it is contraindicated in several pathological conditions. Activated hepatic stellate cells (HSCs) are the main cells for fibrotic tissue synthesis, such as that of alpha-smooth muscle actin (α-SMA). This study aimed to determine whether serum α-SMA levels are a suitable noninvasive, sensitive, and reliable liver fibrosis marker. Fibrosis was induced in male Wistar rats chronic CCl administration. Fibrosis was determined in the liver tissues by quantifying the hydroxyproline content and visualized using Masson's trichrome staining. Rats chronically administered CCl exhibited a progressive increment in the hepatic collagen content, as well as both hepatic and serum α-SMA levels in a time-dependent manner. Moreover, serum levels of α-SMA significantly correlated with hepatic α-SMA levels ( ≤ 0.001), as well as with the severity of liver fibrosis ( ≤ 0.001). These findings suggest that increased levels of serum α-SMA can be considered a potential reliable and noninvasive biomarker for early liver fibrosis.
纤维化的严重程度是慢性肝病患者治疗过程的核心；因此，早期发现肝纤维化对于及时的治疗干预至关重要。肝活检是诊断肝纤维化的金标准；然而，在几种病理情况下是禁忌的。活化的肝星状细胞（HSCs）是纤维化组织合成的主要细胞，如α-平滑肌肌动蛋白（α-SMA）。本研究旨在确定血清α-SMA 水平是否是一种合适的非侵入性、敏感和可靠的肝纤维化标志物。通过定量羟脯氨酸含量并用 Masson 三色染色观察，在雄性 Wistar 大鼠中慢性 CCl 给药诱导纤维化。纤维化在肝组织中确定。慢性给予 CCl 的大鼠表现出肝胶原含量的逐渐增加，以及肝和血清 α-SMA 水平的时间依赖性增加。此外，血清 α-SMA 水平与肝内 α-SMA 水平显著相关（≤0.001），与肝纤维化严重程度也显著相关（≤0.001）。这些发现表明，血清 α-SMA 水平升高可被认为是早期肝纤维化的一种潜在可靠的非侵入性生物标志物。
