关键词: 非酒精性脂肪性肝病, 2型糖尿病, 利拉鲁肽, 核苷酸结合寡聚化结构域样受体家族吡啉结构域蛋白3, 含CARD结构域的凋亡相关颗粒样蛋白, 半胱氨酸天冬氨酸蛋白酶1, 治疗

Abstract: Objective The aim of this study was to investigate the efficacy of liraglutide in the treatment of patients with nonalcoholic fatty liver disease (NAFLD) and concomitant diabetes mellitus type two (T2DM) and its impact on peripheral blood mononuclear cell (PBMC) nucleotide-binding oligomerization domain-like receptor family pyrin containing domain protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and cysteine aspartate protease 1 (caspase-1) levels. Methods 106 patients with NAFLD and T2DM were enrolled in our hospital between January 2022 and January 2025, and were randomly assigned to receive oral metformin and acarbose in 53 cases in control, or intravenous liraglutide at base of metformin and acarbose in another 53 cases in observation for six months. PBMC NLRP3, Caspase-1 and ASC mRNA loads were detected by qRT-PCR, and serum malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were routinely assayed. Results After treatment, serum biochemical parameters in the observation improved much superior to in the control(P<0.05); fasting plasm glucose, 2-hour postprandial blood glucose, glycated hemoglobin, fasting insulin and HOMA-IR were (5.9±1.1)mmol/L, (7.3±1.0)mmol/L, (6.2±0.7)%, (9.2±1.8)μIU/ml and (2.5±0.5), all significantly lower than [(6.5±1.3)mmol/L, (8.7±1.5)mmol/L, (7.0±1.0)%, (13.4±2.3)μIU/ml and (3.1±0.4), respectively, P<0.05] in the control; PBMC NLRP3, Caspase-1 and ASC mRNA loads were (1.1±0.2), (1.2±0.3) and (1.0±0.2), all much lower than [(1.7±0.3), (1.6±0.4) and (1.5±0.3), respectively, P<0.05] in the control; serum MDA level was (7.3±1.5)nmol/mL, much lower than [(10.2±2.1)nmol/mL, P<0.05], while serum SOD and GSH-Px levels were (134.6±7.5)U/L and (153.7±14.0)U/L, both much higher than [(117.2±8.3)U/L and (129.1±13.9)U/L, respectively, P<0.05] in the control group. Conclusion Liraglutide has satisfactory efficacy in the treatment of patients with NAFLD and T2DM, improving glucolipid metabolism, which might be related to decreasing PBMC NLRP3, Caspase-1 and ASC loads.

Key words: Nonalcoholic fatty liver disease, Type 2 Diabetes mellitus, Liraglutide, Nucleotide binding oligomerization domain-like receptor family pyrin containing domain protein 3, Apoptosis-associated speck-like protein containing a CARD, Cysteine aspartate protease 1, Therapy