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Volume 39 Issue 5
Sep.  2021
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JIANG Xiaona, PAN Junjie, YU Yanan, TIAN Zibin. Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 465-467, 475. doi: 10.12206/j.issn.1006-0111.202103002
Citation: JIANG Xiaona, PAN Junjie, YU Yanan, TIAN Zibin. Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 465-467, 475. doi: 10.12206/j.issn.1006-0111.202103002

Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver

doi: 10.12206/j.issn.1006-0111.202103002
  • Received Date: 2021-01-13
  • Rev Recd Date: 2021-05-16
  • Available Online: 2021-09-28
  • Publish Date: 2021-09-25
  •   Objective  To observe the effect of tiopronin combined with glutathione on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT),blood fat and laminin (LN) in patients with non-alcoholic fatty liver.  Methods  A total of 84 non-alcoholic fatty liver patients admitted to our hospital from March 2018 to September 2019 were selected and randomly divided into control group and observation group, with 42 cases in each group. The control group was treated with tiopronin, and the observation group was treated with glutathione and tiopronin. The levels of ALT, AST, GGT and blood fat were recorded and compared before and after treatment.  Results  After treatment, the levels of ALT, AST and GGT in the two groups were significantly lower than before treatment (P<0.05). After treatment, the levels of ALT, AST, and GGT in the observation group were different from those in the control group, which was statistically significant (P<0.05). Before treatment, there was no difference in serum TC, TG, and LDL levels between the two groups, which was not statistically significant (P>0.05). The above-mentioned serum levels of the observation group after treatment were lower than those in the control group, and there was a difference, which was statistically significant (P<0.05); the levels of PCⅢ, PCⅣ, and LN in the treatment group after treatment were significantly lower than those of the control group. The difference was statistically significant (P<0.05).  Conclusion  The application of tiopronin combined with glutathione in the treatment of non-alcoholic fatty liver can promote the recovery of liver function and reduce the concentrations of TC, TG and LDL, which is worthy of clinical promotion.
  • [1] 吴挺丰, 廖献花, 钟碧慧. 中国部分地区非酒精性脂肪肝病的流行情况[J]. 临床肝胆病杂志, 2020, 36(6):1370-1373. doi:  10.3969/j.issn.1001-5256.2020.06.039
    [2] 郭宏雅, 付远飞, 刘惠婷, 等. 血府逐瘀汤与加味二陈汤对小鼠非酒精性脂肪肝的作用比较[J]. 中国实验方剂学杂志, 2020, 26(12):71-77.
    [3] 唐标, 尹抗抗. 降脂理肝汤对高脂饮食诱导的非酒精性脂肪肝病大鼠非经典的细胞焦亡途径的影响[J]. 中国免疫学杂志, 2020, 36(3):267-271. doi:  10.3969/j.issn.1000-484X.2020.03.003
    [4] 叶长江, 叶志伟. 中药联合硫普罗宁与多烯磷脂酰胆碱治疗非酒精性脂肪肝40例[J]. 中西医结合肝病杂志, 2016, 26(5):302-304.
    [5] MO'MEN Y S, HUSSEIN R M, KANDEIL M A. A novel chemoprotective effect of tiopronin against diethylnitrosamine-induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK-P53 signalling cascade[J]. Clin Exp Pharmacol Physiol,2020,47(2):322-332. doi:  10.1111/1440-1681.13204
    [6] 韩静, 李亚伟, 刘艳萍, 等. 银杏黄酮对非酒精性脂肪肝大鼠肝脏组织中脂质和炎症因子水平的影响[J]. 郑州大学学报(医学版), 2020, 55(1):100-103.
    [7] 何剑, 阳学风. 甘草酸二铵肠溶胶囊联合硫普罗宁肠溶片治疗非酒精性脂肪肝的临床研究[J]. 中国临床药理学杂志, 2019, 35(9):833-835.
    [8] ROMUALDO G R, SILVA E D A, DA SILVA T C, et al. Burdock (Arctium lappaL.) root attenuates preneoplastic lesion development in a diet and thioacetamide-induced model of steatohepatitis-associated hepatocarcinogenesis[J]. Environ Toxicol,2020,35(4):518-527. doi:  10.1002/tox.22887
    [9] QI J, KIM J W, ZHOU Z X, et al. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice[J]. Am J Pathol,2020,190(1):68-81. doi:  10.1016/j.ajpath.2019.09.011
    [10] 吴敏, 吴克芹. 还原型谷胱甘肽与硫普罗宁治疗药源性肝病的疗效研究[J]. 中国现代药物应用, 2020, 14(8):159-160.
    [11] 董晋钢, 董晋瑛. 美他多辛联合硫普罗宁治疗酒精性肝病的疗效观察[J]. 中国药房, 2017, 28(8):1091-1094. doi:  10.6039/j.issn.1001-0408.2017.08.23
    [12] YANG H, YANG T T, HENG C, et al. Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice[J]. Phytother Res,2019,33(12):3140-3152. doi:  10.1002/ptr.6486
    [13] 刘俊英, 刘洋, 李涵, 等. 谷胱甘肽复方注射液对免疫性肝纤维化大鼠肝组织钙调素表达的影响[J]. 中华肝脏病杂志, 2019, 27(8):628-633. doi:  10.3760/cma.j.issn.1007-3418.2019.08.008
    [14] 庞红全, 王刚, 杨帆, 等. 还原型谷胱甘肽联合自拟降脂方对酒精性脂肪肝患者血清酶及脂质过氧化水平的影响[J]. 解放军医药杂志, 2016, 28(7):78-81. doi:  10.3969/j.issn.2095-140X.2016.07.021
    [15] VALACHOVA K, SVIK K, BIRO C, et al. Skin wound healing with composite biomembranes loaded by tiopronin or captopril[J]. J Biotechnol,2020,310:49-53. doi:  10.1016/j.jbiotec.2020.02.001
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Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver

doi: 10.12206/j.issn.1006-0111.202103002

Abstract:   Objective  To observe the effect of tiopronin combined with glutathione on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT),blood fat and laminin (LN) in patients with non-alcoholic fatty liver.  Methods  A total of 84 non-alcoholic fatty liver patients admitted to our hospital from March 2018 to September 2019 were selected and randomly divided into control group and observation group, with 42 cases in each group. The control group was treated with tiopronin, and the observation group was treated with glutathione and tiopronin. The levels of ALT, AST, GGT and blood fat were recorded and compared before and after treatment.  Results  After treatment, the levels of ALT, AST and GGT in the two groups were significantly lower than before treatment (P<0.05). After treatment, the levels of ALT, AST, and GGT in the observation group were different from those in the control group, which was statistically significant (P<0.05). Before treatment, there was no difference in serum TC, TG, and LDL levels between the two groups, which was not statistically significant (P>0.05). The above-mentioned serum levels of the observation group after treatment were lower than those in the control group, and there was a difference, which was statistically significant (P<0.05); the levels of PCⅢ, PCⅣ, and LN in the treatment group after treatment were significantly lower than those of the control group. The difference was statistically significant (P<0.05).  Conclusion  The application of tiopronin combined with glutathione in the treatment of non-alcoholic fatty liver can promote the recovery of liver function and reduce the concentrations of TC, TG and LDL, which is worthy of clinical promotion.

JIANG Xiaona, PAN Junjie, YU Yanan, TIAN Zibin. Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 465-467, 475. doi: 10.12206/j.issn.1006-0111.202103002
Citation: JIANG Xiaona, PAN Junjie, YU Yanan, TIAN Zibin. Effect of tiopronin combined with glutathione on biochemical indicators of patients with non-alcoholic fatty liver[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(5): 465-467, 475. doi: 10.12206/j.issn.1006-0111.202103002
  • 近年来,我国高血脂、肥胖症以及代谢综合征等疾病的患病人数不断增加,非酒精性脂肪肝患病率已呈现上升势头[1]。非酒精性脂肪肝(NAFLD)是一种非酒精造成的肝组织病理学改变的代谢应激相关性疾病[2]。主要临床表现为不同程度的乏力,伴随血清肝功能指标升高,严重时可导致肝硬化,威胁着患者生命健康。目前临床治疗NAFLD有了新的发展,新型药物逐渐出现,但是,患者的临床疗效以及相关肝功能的恢复情况有待进一步研究[3]。国内研究表明[4, 5],硫普罗宁联合谷胱甘肽治疗NAFLD患者,可明显改善血清肝功能,缓解症状,对于非酒精性脂肪肝的治疗具有一定临床意义。

  • 自2018年3月至2019年9月,选取我院收治的非酒精性脂肪肝患者84例,随机分为对照组和观察组,每组42人,其中对照组男28例,女14例,平均年龄(51.36±6.42)岁,分级:轻度7例,中度28例,重度7例,合并高脂血症19例、高血压13例、2型糖尿病8例;观察组男26例,女16例,平均年龄(52.17±7.02)岁,分级:轻度5例,中度29例,重度8例,合并高脂血症20例、高血压11例、2型糖尿病11例。两组患者在性别、年龄、分级、合并症等基线资料差异不显著(P>0.05,表1),具有可比性。

    组别例数性别平均年龄/岁分级 合并症
    轻度中度重度高脂血症高血压2型糖尿病
    对照组42281451.36±6.427287 1913 8
    观察组42261652.17±7.025298201111
    t20.210.550.420.62
    P0.650.580.810.73
  • 诊断标准:非酒精性脂肪肝诊断参照《中华医学会肝脏病学分会脂肪肝和酒精性肝病学组2010年制定的NAFLD》[6]诊断标准。

    纳入标准:①符合非酒精性脂肪肝诊断标准;②25~65岁;③患者近期均未服用保护肝脏类药物;④患者均接受回访,并配合开展工作;⑤本医院伦理委员会通过该项研究。排除标准:①患者年龄<25岁或>65岁者;②酒精性或者病毒性肝炎患者;③存在心脏、肝脏、肾脏等严重疾病的患者;④不接受回访,或者不能配合临床治疗的患者;⑤基本临床资料不全者。

  • 两组患者均予以开展适量性的体育锻炼和低脂饮食,对照组给予硫普罗宁(江苏迪赛诺制药有限公司,批准文号:国药准字H20055040)治疗,用法如下:0.2 g/次,3次/d。观察组在对照组的基础上加用谷胱甘肽(山东金城生物药业有限公司,批准文号:国药准字H20123300)治疗,用法如下:1.2 g/次,3次/d。所有患者治疗30 d为一疗程,治疗3疗程。

  • 采用全自动生化分析仪测定两组患者肝功能指标[谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转移酶(GGT)]和血脂水平;采用夹心酶联免疫吸附试验法检测患者肝纤维化指标:Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(PCⅣ)、层黏蛋白(LN)。

  • 统计学处理采用SPSS 25.0,t检验:计量资料,χ2检验:计数资料。P<0.05为差异显著,具有统计学意义。

  • 经治疗,两组ALT、AST、GGT水平较治疗前明显下降(P<0.05),治疗后观察组ALT、AST、GGT水平低于对照组(P<0.05),存在统计学差异,见表2

    组别例数ALTASTGGT
    对照组:治疗前42101.12±29.8557.44±19.5488.27±24.34
    治疗后 51.28±18.24#48.25±12.23#56.34±18.72#
    观察组:治疗前42103.11±28.4658.07±18.3379.15±23.87
    治疗后 38.24±20.13#*41.13±11.87#*42.26±16.32#*
    #P<0.05,与组内治疗前比较;*P<0.05,与对照组治疗后比较
  • 治疗前,两组血清血脂(TC、TG、LDL-C)水平不存在差异,不具有统计学意义(P>0.05);治疗后观察组上述血清水平低于对照组(P<0.05),差异具有统计学意义,见表3

    组别例数TCTGLDL-C
    对照组:治疗前427.12±1.254.44±1.544.57±1.24
    治疗后 4.52±1.24#3.25±1.23#3.15±1.12#
    观察组:治疗前427.06±1.464.37±1.334.61±1.23
    治疗后 3.84±0.93#*2.13±1.17#*2.56±1.06#*
    #P<0.05,与组内治疗前比较;*P<0.05,与对照组治疗后比较
  • 治疗组治疗后PCⅢ、PCⅣ、LN水平同对照组比较,存在显著差异(P<0.05),差异有统计学意义,见表4

    组别例数PCⅢPCⅣLN
    对照组:治疗前42124.51±22.4572.45±12.15113.24±21.42
    治疗后103.71±21.42#59.21±11.28#97.26±19.23#
    观察组:治疗前42125.26±23.1772.52±13.21114.17±22.31
    治疗后92.54±17.86#*53.81±12.63#*85.62±18.67#*
    #P<0.05,与组内治疗前比较;*P<0.05,与对照组治疗后比较
  • NAFLD是一种非长期饮酒所致,无明显肝损伤的临床病理综合征。其主要的特征是弥漫性肝细胞大泡性脂肪变[7]。流行病学调查显示,其发病率已超过病毒性以及酒精性引起的肝病。NAFLD主要包括脂肪性肝炎、单纯性脂肪肝、肝硬化三种类型[8]。目前关于NAFLD的发病机制临床上尚无明确,较为公认的就是“二次打击”学说,即由胰岛素抵抗和氧化应激、脂质过氧化、炎性细胞因子释放形成。如得不到及时治疗,最终可引发肝细胞癌[9]。因此,NAFLD及时有效治疗显得尤为必要。现有治疗方法上没有特效药,主要进行针对性的治疗,如调节血脂、缓解肝功能损伤等。

    研究证实[10],硫普罗宁、谷光甘肽片等是近年来可明显缓解NAFLD患者病情,改善肝功能的药物。硫普罗宁是一类含游离巯基的甘氨酸衍生物。该药物可以结合自由基,进而将自由基清除,另外可以升高肝细胞内线粒体ATP酶的活性,增加肝细胞内线粒体ATP,保护线粒体某些巯基的功能,促进肝糖原的出现,并达到抑制脂质代谢的目的,最终改善肝细胞的功能和结构,修复肝细胞以及再生;其次参与调节肝细胞中糖、脂肪、蛋白质的代谢,转化多余的脂肪,将积累在肝脏的三酰甘油清理出去;最后可以把肝细胞内谷胱甘肽维持在一定水平,实现抑制肝细胞内脂质的转化。硫普罗宁被临床上广泛应用于治疗肝病,具有效果显著、不良反应小的优势。董晋钢等[11]研究证实,硫普罗宁可明显降低酒精性肝病患者血清ALT、AST、TC、TG水平以及血清PCⅢ、PCⅣ、LN等水平,疗效较好,且安全性高。谷胱甘肽是一种可中和氧自由基的甘油醛磷酸脱氢酶以及乙二醛酶和磷酸丙糖脱氢酶辅基,通过参与机体内糖、脂质、蛋白质的代谢,减少脂质的过氧化和应激作用;另外可有效抑制和中和氧自由基,减少机体产生氧自由基,从而保护肝细胞膜及促进肝功能恢复[12]。刘俊英等[13]研究显示,谷胱甘肽可明显降低纤维化大鼠肝组织RGN mRNA相对表达量及蛋白表达相对表达量,纤维化明显减轻,提示该药物可能在肝纤维化发生发展过程中起重要作用。上述两种药物联合使用,可减轻脂肪肝和纤维化程度,有效改善肝功能指标,促进肝功能恢复,且安全可靠。本研究发现经治疗,两组ALT、AST、GGT水平较治疗前明显下降,观察组治疗后,ALT、AST、GGT水平明显低于对照组,差异具有统计学意义;治疗后观察组血清TC、TG、LDL水平明显低于对照组,差异具有统计学意义;治疗组患者PCⅢ、PCⅣ、LN水平同对照组比较,均显著降低,同国内外研究结果基本一致[14-15]

    综上所述,应用硫普罗宁联合谷胱甘肽治疗非酒精性脂肪肝,可促进肝功能的恢复,降低血脂水平,降低肝纤维化程度,值得临床推广。

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