瑞舒伐他汀联合双环醇片通过抗纤维化机制治疗非酒精性脂肪性肝炎的研究
|
摘要
目的探讨瑞舒伐他汀联合双环醇片治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的临床效果和作用机制。方法将120例NASH患者随机分为单纯瑞舒伐他汀治疗组(R组)和瑞舒伐他汀联合双环醇片治疗组(R+D组),每组60例。比较2组治疗前后血清肝功能、血脂、肝纤维化指标和肝穿刺组织肝纤维化相关指标。结果治疗后,2组丙氨酸转氨酶(glutamic pyruvic transaminase,ALT)、天冬氨酸转氨酶(glutamic oxaloacetic transaminase,AST)和谷氨酰转移酶(glutamyl transpeptadase,GGT)水平均明显低于治疗前,R+D组ALT、AST和GGT水平均明显低于R组,差异有统计学意义(P<0.05)。2组总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平均明显低于治疗前,高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)明显高于治疗前,差异有统计学意义(P<0.05);2组TC、TG、HDL-C和LDL-C水平差异均无统计学意义(P>0.05)。R+D组透明质酸(haluronic acid,HA)、层黏蛋白(laminin,LN)、Ⅲ型前胶原肽(procollagenⅢ,PC-Ⅲ)和Ⅳ型胶原(collagenⅣ,C-Ⅳ)水平均明显低于治疗前,R+D组HA、LN、PC-Ⅲ和C-Ⅳ均明显低于R组,差异有统计学意义(P<0.05)。R+D组肝脏胶原Ⅰ、胶原Ⅳ和纤维黏连蛋白mRNA和蛋白表达均明显低于治疗前,R+D组肝脏胶原Ⅰ、胶原Ⅳ和纤维黏连蛋白mRNA和蛋白的表达均明显低于R组,差异有统计学意义(P<0.05)。结论瑞舒伐他汀联合双环醇片治疗NASH患者的肝功能和肝纤维化指标显著改善,其疗效优于单纯瑞舒伐他汀治疗。
Objective To explore the clinical efficacy and mechanism of rosuvastatin combined with bicyclol tablets on non-alcoholic steatohepatitis(NASH). Methods A total of 120 NASH patients were randomly divided into the rosuvastatin treatment group and the rosuvastatin combined with bicyclol tablets, 60 patients in each group. The changes of serum liver function, blood lipid and liver fibrosis index as well as liver tissues fibrosis related index were observed before and after treatment in the two groups. Results After treatment, the glutamic pyruvic transaminase(ALT), glutamyl transpeptadase(AST) and glutamyl transpeptadase(GGT) levels of the two groups were significantly lower than that before treatment, and the ALT, AST and GGT levels of the R+D group were significantly lower than those of the R group, with statistically significant differences(P<0.05). After treatment, 2 groups of total cholesterol(TC), triglyceride(TG) and low density lipoprotein cholesterol(LDL-C) level was lower than that before treatment, high density lipoprotein cholesterol(HDL-C) were significantly higher than those before treatment, the difference was statistically significant(P<0.05). There was no significant difference in TC, TG, HDL-C and LDL-C levels between the two groups after treatment(P>0.05). Hyaluronic acid(HA), laminin(LN), procollagen Ⅲ(PC-Ⅲ) and collagen Ⅳ(C-Ⅳ) level of R+D groups was lower than that before treatment, HA, LN, PC-Ⅲ and C-Ⅳof R+D group was lower than that in R group, the difference was statistically significant(P<0.05). The mRNA and protein expressions of collagen Ⅰ, collagen Ⅳ and fibronectin in the liver of R+D group were significantly lower than those before treatment, and the mRNA and protein expressions of collagen Ⅰ, collagen Ⅳ and fibronectin in the liver of R+D group were significantly lower than those of the R group, with statistically significant differences(P<0.05). Conclusion The indexes of liver function and liver fibrosis in NASH patients were significantly improved after the combined treatment of rosuvastatin and bicyclol tablets, and the curative effects were superior to that of rosuvastatin alone.
Objective To explore the clinical efficacy and mechanism of rosuvastatin combined with bicyclol tablets on non-alcoholic steatohepatitis(NASH). Methods A total of 120 NASH patients were randomly divided into the rosuvastatin treatment group and the rosuvastatin combined with bicyclol tablets, 60 patients in each group. The changes of serum liver function, blood lipid and liver fibrosis index as well as liver tissues fibrosis related index were observed before and after treatment in the two groups. Results After treatment, the glutamic pyruvic transaminase(ALT), glutamyl transpeptadase(AST) and glutamyl transpeptadase(GGT) levels of the two groups were significantly lower than that before treatment, and the ALT, AST and GGT levels of the R+D group were significantly lower than those of the R group, with statistically significant differences(P<0.05). After treatment, 2 groups of total cholesterol(TC), triglyceride(TG) and low density lipoprotein cholesterol(LDL-C) level was lower than that before treatment, high density lipoprotein cholesterol(HDL-C) were significantly higher than those before treatment, the difference was statistically significant(P<0.05). There was no significant difference in TC, TG, HDL-C and LDL-C levels between the two groups after treatment(P>0.05). Hyaluronic acid(HA), laminin(LN), procollagen Ⅲ(PC-Ⅲ) and collagen Ⅳ(C-Ⅳ) level of R+D groups was lower than that before treatment, HA, LN, PC-Ⅲ and C-Ⅳof R+D group was lower than that in R group, the difference was statistically significant(P<0.05). The mRNA and protein expressions of collagen Ⅰ, collagen Ⅳ and fibronectin in the liver of R+D group were significantly lower than those before treatment, and the mRNA and protein expressions of collagen Ⅰ, collagen Ⅳ and fibronectin in the liver of R+D group were significantly lower than those of the R group, with statistically significant differences(P<0.05). Conclusion The indexes of liver function and liver fibrosis in NASH patients were significantly improved after the combined treatment of rosuvastatin and bicyclol tablets, and the curative effects were superior to that of rosuvastatin alone.
引文
[1] Hashimoto E,Tokushige K,Ludwig J. Diagnosis and classification of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis:current concepts and remaining challenges[J]. Hepatol Res,2015,45(1):20-28.
[2] Fiorucci S,Biagioli M,Distrutti E. Future trends in the treatment of non-alcoholic steatohepatitis[J]. Pharmacol Res,2018,134:289-298.
[3] Dumitrascu DL,Neuman MG. Non-alcoholic fatty liver disease:an update on diagnosis[J]. Clujul Med,2018,91(2):147-150.
[4] Anstee QM,Targher G,Day CP. Progression of NAFLD to diabetes mellitus,cardiovascular disease or cirrhosis[J]. Nat Rev Gastroenterol Hepatol,2013,10(6):330-344.
[5] 李烨,李燕,刘耕陶.双环醇对实验性肝纤维化的防护作用及分子机制[J].中华医学杂志,2004,84(24):2096-2101.
[6] Ekstedt M,Franzén LE,Mathiesen UL,et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes[J]. Hepatology,2006,44(4):865-873.
[7] Argo CK,Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis[J]. Clin Liver Dis,2009,13(4):511-531.
[8] Ratziu V,Bellentani S,Cortez-Pinto H,et al. A position statement on NAFLD/NASH based on the EASL 2009 special conference[J]. J Hepatol,2010,53(2):372-384.
[9] McPherson S,Hardy T,Henderson E,et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies:implications for prognosis and clinical management[J]. J Hepatol,2015,62(5):1148-1155.
[10] Kargiotis K,Athyros VG,Giouleme O,et al. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome[J]. World J Gastroenterol,2015,21(25):7860-7868.
[11] Liu GT,Li Y,Wei HL,et al. Mechanism of protective action of bicyclol against CCl-induced liver injury in mice[J]. Liver Int,2005,25(4):872-879.
[12] Yao XM,Li Y,Li HW,et al. Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice[J]. Can J Physiol Pharmacol,2016,94(1):1-8.
[13] Shang W,Feng Y,Li J,et al. Effect of bicyclol tablets on drug induced liver injuries after kidney transplantation[J]. Open Med(Wars),2017,12:62-69.
[14] Liu GT. Bicyclol:a novel drug for treating chronic viral hepatitis B and C[J]. Med Chem,2009,5(1):29-43.
[15] Schuppan D,Schattenberg JM. Non-alcoholic steatohepatitis:pathogenesis and novel therapeutic approaches[J]. J Gastroenterol Hepatol,2013,28(Suppl 1):68-76.
[16] 袁丽君,南月敏.Fas/FasL系统诱导非酒精性脂肪性肝炎中细胞凋亡的分子生物学机制[J].河北医科大学学报,2009,30(3):312-314.
[2] Fiorucci S,Biagioli M,Distrutti E. Future trends in the treatment of non-alcoholic steatohepatitis[J]. Pharmacol Res,2018,134:289-298.
[3] Dumitrascu DL,Neuman MG. Non-alcoholic fatty liver disease:an update on diagnosis[J]. Clujul Med,2018,91(2):147-150.
[4] Anstee QM,Targher G,Day CP. Progression of NAFLD to diabetes mellitus,cardiovascular disease or cirrhosis[J]. Nat Rev Gastroenterol Hepatol,2013,10(6):330-344.
[5] 李烨,李燕,刘耕陶.双环醇对实验性肝纤维化的防护作用及分子机制[J].中华医学杂志,2004,84(24):2096-2101.
[6] Ekstedt M,Franzén LE,Mathiesen UL,et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes[J]. Hepatology,2006,44(4):865-873.
[7] Argo CK,Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis[J]. Clin Liver Dis,2009,13(4):511-531.
[8] Ratziu V,Bellentani S,Cortez-Pinto H,et al. A position statement on NAFLD/NASH based on the EASL 2009 special conference[J]. J Hepatol,2010,53(2):372-384.
[9] McPherson S,Hardy T,Henderson E,et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies:implications for prognosis and clinical management[J]. J Hepatol,2015,62(5):1148-1155.
[10] Kargiotis K,Athyros VG,Giouleme O,et al. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome[J]. World J Gastroenterol,2015,21(25):7860-7868.
[11] Liu GT,Li Y,Wei HL,et al. Mechanism of protective action of bicyclol against CCl-induced liver injury in mice[J]. Liver Int,2005,25(4):872-879.
[12] Yao XM,Li Y,Li HW,et al. Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice[J]. Can J Physiol Pharmacol,2016,94(1):1-8.
[13] Shang W,Feng Y,Li J,et al. Effect of bicyclol tablets on drug induced liver injuries after kidney transplantation[J]. Open Med(Wars),2017,12:62-69.
[14] Liu GT. Bicyclol:a novel drug for treating chronic viral hepatitis B and C[J]. Med Chem,2009,5(1):29-43.
[15] Schuppan D,Schattenberg JM. Non-alcoholic steatohepatitis:pathogenesis and novel therapeutic approaches[J]. J Gastroenterol Hepatol,2013,28(Suppl 1):68-76.
[16] 袁丽君,南月敏.Fas/FasL系统诱导非酒精性脂肪性肝炎中细胞凋亡的分子生物学机制[J].河北医科大学学报,2009,30(3):312-314.