GLP-1受体激动剂联合二甲双胍片对NAFLD患者肝纤维化及PTX3、TXNIP的影响

Effect of GLP-1 receptor agonist combined with metformin tablets on liver fibrosis,PTX3 and TXNIP in patients with NAFLD

目的:探讨GLP-1受体激动剂联合二甲双胍片对非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)患者肝纤维化及血清五聚体蛋白-3(pentraxin 3,PTX3)、硫氧还蛋白结合蛋白(thioredoxin interacting protein,TXNIP)的影响。方法:选取2016年5月-2019年6月本院收治的308例NAFLD患者,随机分为观察组和对照组,各154例。对照组患者予以二甲双胍片进行治疗,观察组患者在对照组的基础上联合GLP-1受体激动剂利拉鲁肽进行治疗,比较两组患者治疗前后总胆固醇(total cholesterol,TC)、三酰甘油(triacylglycerol,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、空腹血糖(fasting plasma glucose,FPG)、餐后2 h血糖(postprandial 2 h plasma glucose,2 h PG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)等血糖血脂指标,空腹血糖、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(insulin resistance index,IRI)(HOMA-IR)等胰岛素抵抗指标,血清透明质酸(serum hyaluronic acid,HA)、层黏蛋白(laminin,LN)、IV型胶原(IV collagen,IV-C)、Ⅲ型前胶原(Ⅲprocollagen,PCⅢ)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)等肝纤维化指标和肝纤维化评分及PTX3和TXNIP水平表达情况。结果:治疗后,两组患者TC、TG、LDL-C、FPG、2 h PG、HbA1c等指标水平较治疗前降低,且观察组较对照组更低(P<0.05),而两组HDL-C水平较治疗前升高,且观察组较对照组更高(P<0.05)。治疗后,观察组FPG、FINS、HOMA-IR等指标水平较治疗前降低,且低于对照组(P<0.05),而治疗后对照组FPG较治疗前升高,FINS、HOMA-IR较治疗前降低(P<0.05)。治疗后,两组患者LN、IV-C、PCⅢ、HA、AST、ALT等肝纤维化指标水平及NAFLDFS评分较治疗前显著降低,且观察组较对照组更低(P<0.05)。治疗后,两组患者血清TXNIP、PTX3水平较治疗前降低,且观察组血清TXNIP、PTX3水平较对照组更低,差异有统计学意义(P<0.05)。结论:GLP-1受体激动剂联合二甲双胍片可有效缓解NAFLD患者肝纤维化情况,改善胰岛素抵抗情况,降低血清PTX3、TXNIP水平表达,进而改善患者肝功能。

Objective:To explore the effect of GLP-1 receptor agonist combined with metformin tablets on liver fibrosis,PTX3 and TXNIP in patients with NAFLD.Methods:308 non-alcoholic fatty liver disease(NAFLD)patients admitted to our hospital from May 2016 to June 2019 were selected and randomly divided into the observation group and control group,with 154 cases in each group.Patients in the control group were treated with metformin tablets,and patients in the observation group were treated with the GLP-1 receptor agonist liraglutide combining with metformin tablets.The total cholesterol(TC)and triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),fasting plasma glucose(FPG),postprandial 2 h blood glucose(2 h PG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(HOMA-IR),serum hyaluronic acid(HA),laminin(LN),type IV collagen(IV-C),ⅢType procollagen(PCⅢ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),liver fibrosis score(NAFLDFS),serum pentameric protein-3(PTX3)and serum thioredoxin,and the expression level of protein interaction protein(TXNIP)of the two groups were compared before and after treatment.Results:After treatment,the levels of TC,TG,LDL-C,FPG,2hPG,HbA1c in the two groups were lower than those before treatment,and the levels of above indicators in the observation group was lower than those in the control group(P<0.05),while the HDL-C levels in the two groups were higher than those before treatment,and the HDL-C level of the observation group was higher than that of the control group(P<0.05).After treatment,the levels of FPG,FINS and HOMA-IR in the observation group were lower than those before treatment,and were significantly lower than those in the control group(P<0.05).The FPG level in the control group was higher than that before treatment,while FINS and HOMA-IR were higher after treatment(P<0.05).After treatment,the levels of liver fibrosis indexes such as LN,IV-C,PCⅢ,HA,AST,ALT and NAFLDFS score of the two groups were significantly lower than those before treatment,and the levels of above indicators of observation group was lower than those in the control group(P<0.05).The serum TXNIP and PTX3 levels of patients in the two groups were significantly lower than those before treatment,and they were lower in the observation group than those in the control group,and the differences were statistically significant(P<0.05).Conclusion:GLP-1 receptor agonists combined with metformin tablets could effectively alleviate liver fibrosis in patients with NAFLD,improve insulin resistance,reduce the expression of serum PTX3 and TXNIP levels,and improve patients’liver function.