Serum level of proteins involved in apoptosis and autophagy in patients with type 2 diabetes and non-alcoholic fatty liver disease

Ya. A. Krasner, V. V. Romanov, O. N. Fazullina, M. F. Osipenko, V. Klimontov
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Abstract

Aim of the study was to estimate the blood serum level of microtubule-associated protein 1 light chain 3 alpha (MAP1LC3alpha), beclin-1 (BECN-1), Bcl-2 (BCL-2), caspase-3 (CASP3) and autophagy related 5 (ATG-5) protein as potential markers of liver fibrosis in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD).Material and methods. A single center cross-sectional observational study was performed. Seventy four patients with T2D and NAFLD were included, 23 men and 51 women, aged 18 to 74 years. Transient elastography was used for the assessment of liver fibrosis. The severity of fibrosis was estimated using the Metavir sсore. In addition, indirect liver fibrosis indices APRI and FIB-4 were calculated. Serum concentration of MAP1LC3alpha, BECN-1, BCL-2, CASP and ATG-5 was measured by ELISA. We applied ROC analysis to assess the value of studied indicators in diagnosis of liver fibrosis.Results. Liver fibrosis stage F1 was verified in 16 subjects, stage F2 in 12, stage F3 in 7, and stage F4 in 19 individuals. Patients with advanced liver fibrosis (stage 3-4) when compared to those without fibrosis (stage 0–2) had higher content of MAP1LC3alpha (p = 0.01) and BECN-1 (p = 0.01). There were no significant differences in the level of BCL-2, CASP3 and ATG-5 between patients with different severity of fibrosis. In the ROC analysis, MAP1LC3alpha and BECN-1 showed significance for the diagnosis of severe liver fibrosis, which, however, did not exceed that of the APRI index.Conclusions. In patients with T2D and NAFLD, serum levels of MAP1LC3alpha and BECN-1 are associated with severe liver fibrosis.
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2 型糖尿病和非酒精性脂肪肝患者血清中参与细胞凋亡和自噬的蛋白质水平
该研究旨在估测作为肝纤维化潜在标志物的微管相关蛋白1轻链3α(MAP1LC3alpha)、beclin-1(BECN-1)、Bcl-2(BCL-2)、Caspase-3(CASP3)和自噬相关5(ATG-5)蛋白在非酒精性脂肪肝(NAFLD)2型糖尿病(T2D)患者中的血清水平。这是一项单中心横断面观察研究。研究纳入了 74 名 T2D 和非酒精性脂肪肝患者,其中男性 23 人,女性 51 人,年龄在 18 至 74 岁之间。瞬态弹性成像技术用于评估肝纤维化。肝纤维化的严重程度使用 Metavir s sore 进行估算。此外,还计算了间接肝纤维化指数 APRI 和 FIB-4。血清中 MAP1LC3alpha、BECN-1、BCL-2、CASP 和 ATG-5 的浓度是通过 ELISA 法测定的。我们应用ROC分析评估了所研究指标在肝纤维化诊断中的价值。16名受试者的肝纤维化程度达到F1期,12名达到F2期,7名达到F3期,19名达到F4期。肝纤维化晚期(3-4期)患者与无肝纤维化患者(0-2期)相比,MAP1LC3alpha(P = 0.01)和BECN-1(P = 0.01)的含量更高。在不同纤维化严重程度的患者之间,BCL-2、CASP3 和 ATG-5 的含量没有明显差异。在ROC分析中,MAP1LC3alpha和BECN-1在严重肝纤维化诊断中显示出显著性,但并未超过APRI指数。在患有 T2D 和 NAFLD 的患者中,血清中 MAP1LC3alpha 和 BECN-1 的水平与严重肝纤维化有关。
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