Abstract: Objective　To study the effect of diamine glycyrrhizinate on chronic hepatitis fibrosis mediated by C-reactive protein (CRP) and transforming growth factor β (TGF-β). Methods　From September to December 2021, 50 rats who were 8 weeks old and whose body weight was (200±20) g/mouse were randomly divided into a control group, a model group, a high-dose group, a medium-dose group, and a low-dose group, with 10 ones in each group. The chronic hepatitis fibrosis models were established using concanol protein A; high, medium, and low doses of enedrine glycyrrheate were administered by gavage. The control group and the model group were given equal doses of normal saline. The liver pathological changes and serum levels of CRP, alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), laminin (LN), collagen Ⅰ (PC Ⅰ), collagen Ⅲ (PC Ⅲ) , and other fibro-related indicators were compared between these groups. The mRNA expressions of CRP, TGF-β, LN, PC Ⅰ, and PC Ⅲ in liver tissue were detected by polymerase chain reaction (PCR). The protein expressions of CRP, TGF-β, LN, PC Ⅰ, and PC Ⅲ in liver tissue were detected by Western Blot. The data were compared between two groups by t test, and between the 5 groups by one-way ANOVA. Results　The levels of CRP, ALT, AST, HA, LN, PC Ⅰ, and PC Ⅲ in the control group were significantly lower than those in the model group [(7.34±1.19) mg/L vs. (121.98±1.37) mg/L, (48.32±16.92) U/L vs. (169.31±20.31) U/L, (29.28±18.12) U/L vs. (163.08±25.97) U/L, (7.98±1.23) mg/L vs. (17.39±1.39) mg/L, (73.20±11.08) μg/L vs. (119.34±14.98) μg/L, (8.09±1.57) μg/L vs. (27.46±2.05) μg/L, and (9.07±1.69) μg/L vs. (29.91±2.17) μg/L; all P<0.05]. Compared with those in the model group, the levels of CRP, ALT, AST, HA, LN, PC Ⅰ, and PC Ⅲ in the low-dose group, the medium-dose group, and the high-dose group decreased as the dose increased [(87.20±1.29) mg/L vs. (53.19±1.23) mg/L vs. (18.29±1.20) mg/L, (112.87±19.28) U/L vs. (87.29±18.78) U/L vs. (57.92±17.38) U/L, (139.98±23.09) U/L vs. (102.35±21.34) U/L vs. (78.98±19.87) U/L, (14.27±1.28) mg/L vs. (10.31±1.27) mg/L vs. (8.38±1.25) mg/L, (102.47±13.37) μg/L vs. (82.37±12.84) μg/L vs. (78.39±12.06) μg/L, (22.98±1.82) μg/L vs. (16.62±1.72) μg/L vs. (10.35±1.68) μg/L, and (23.23±1.79) μg/L vs. (17.45±1.78) μg/L vs. (12.57±1.72) μg/L], with statistical differences (all P<0.05). The mRNA and protein expressions of CRP, TGF-β, LN, PC Ⅰ, and PC Ⅲ in the control group were lower than those in the model group [(0.92±0.23) vs. (2.98±0.32) and (0.87±0.08) vs. (2.94±0.21), (1.19±0.17) vs. (3.29±0.29) and (1.09±0.07) vs. (3.02±0.23), (0.93±0.18) vs. (3.91±0.38) and (1.18±0.10) vs. (3.45±0.26), (1.02±0.22) vs. (4.32±0.32) and (1.08±0.08) vs. (3.96±0.28), and (1.23±0.19) vs. (4.23±0.29) and (1.13±0.10) vs. (3.32±0.23); all P<0.05]. Compared with those in the model group, the mRNA and protein expressions of CRP, TGF-β, LN, PC Ⅰ, and PC Ⅲ in the low-dose group, the medium-dose group, and the high-dose group decreased as the dose increased [(2.21±0.28) vs. (1.97±0.30) vs. (1.39±0.26) and (1.96±0.18) vs. (1.54±0.14) vs. (1.18±0.09), (2.94±0.24) vs. (2.09±0.27) vs. (1.49±0.20) and (2.18±0.21) vs. (1.86±0.19) vs. (1.28±0.14), (3.09±0.30) vs. (2.39±0.26) vs. (1.52±0.25) and (2.46±0.24) vs. (1.87±0.20) vs. (1.37±0.16), (2.93±0.28) vs. (1.82±0.24) vs. (1.28±0.20) and (2.08±0.28) vs. (1.76±0.24) vs. (1.29±0.13), and (3.21±0.25) vs. (2.19±0.28) vs. (1.47±0.24) and (2.87±0.20) vs. (2.09±0.19) vs. (1.21±0.11)], with statistical differences (all P<0.05). Conclusion　A high dose of diamine glycyrrhizinate can alleviate liver fibrosis, and inhibiting the expressions of PCR and TGF-β is a possible molecular mechanism mediating this improvement.

Key words: Chronic hepatitis fibrosis, Diamine glycyrrhizinate, C-reactive protein, Transforming growth factor β

摘要： 目的　探讨甘草酸二胺对C反应蛋白（CRP）、转化生长因子β（TGF-β）介导的慢性肝炎性纤维化的作用研究。方法　2021年9月至12月，选取50只大鼠［8周龄，体质量（200±20）g/只］，分为对照组、模型组、高剂量组、中剂量组、低剂量组，每组10只，采用刀豆蛋白A建立慢性肝炎纤维化模型，采用高、中、低剂量甘草酸二胺灌胃干预，而对照组、模型组给予等剂量生理盐水。比较各组大鼠肝脏病理改变、血清C反应蛋白（CRP）、谷丙转氨酶（ALT）、谷草转氨酶（AST）水平及透明质酸（HA）、层粘连蛋白（LN）、I型胶原蛋白（PC Ⅰ）、Ⅲ型胶原蛋白（PC Ⅲ）等纤维化相关指标含量；采用聚合酶链反应（PCR）检测肝组织CRP、TGF-β、LN、PC Ⅰ、PC Ⅲ mRNA表达；Western blot法检测肝组织CRP、TGF-β、LN、PC Ⅰ、PC Ⅲ蛋白表达情况。组间比较采用t检验，多组间比较采用单因素方差分析。结果　与对照组相比，模型组CRP［（7.34±1.19）mg/L比（121.98±1.37）mg/L］、ALT［（48.32±16.92）U/L比（169.31±20.31）U/L］、AST［（29.28±18.12）U/L比（163.08±25.97）U/L］、HA［（7.98±1.23）mg/L比（17.39±1.39）mg/L］、LN［（73.20±11.08）μg/L比（119.34±14.98）μg/L］、PC Ⅰ［（8.09±1.57）μg/L比（27.46±2.05）μg/L］、PC Ⅲ［（9.07±1.69）μg/L比（29.91±2.17）μg/L］水平均显著升高（均P<0.05）；与模型组比较，随剂量增加，低剂量组、中剂量组、高剂量组CRP［（87.20±1.29）mg/L比（53.19±1.23）mg/L比（18.29±1.20）mg/L］、ALT［（112.87±19.28）U/L比（87.29±18.78）U/L比（57.92±17.38）U/L］、AST［（139.98±23.09）U/L比（102.35±21.34）U/L比（78.98±19.87）U/L］、HA［（14.27±1.28）mg/L比（10.31±1.27）mg/L比（8.38±1.25）mg/L］、LN［（102.47±13.37）μg/L比（82.37±12.84）μg/L比（78.39±12.06）μg/L］、PC Ⅰ［（22.98±1.82）μg/L比（16.62±1.72）μg/L比（10.35±1.68）μg/L］、PC Ⅲ［（23.23±1.79）μg/L比（17.45±1.78）μg/L比（12.57±1.72）μg/L］水平明显降低，差异均有统计学意义（均P<0.05）；与对照组相比，模型组CRP［（0.92±0.23）比（2.98±0.32），（0.87±0.08）比（2.94±0.21）］、TGF-β［（1.19±0.17）比（3.29±0.29），（1.09±0.07）比（3.02±0.23）］、LN［（0.93±0.18）比（3.91±0.38），（1.18±0.10）比（3.45±0.26）］、PC Ⅰ［（1.02±0.22）比（4.32±0.32），（1.08±0.08）比（3.96±0.28）］、PC Ⅲ［（1.23±0.19）比（4.23±0.29），（1.13±0.10）比（3.32±0.23）］mRNA及蛋白表达均显著升高（均P<0.05）；与模型组比较，随剂量增加低剂量组、中剂量组、高剂量组CRP［（2.21±0.28）比（1.97±0.30）比（1.39±0.26），（1.96±0.18）比（1.54±0.14）比（1.18±0.09）］、TGF-β［（2.94±0.24）比（2.09±0.27）比（1.49±0.20），（2.18±0.21）比（1.86±0.19）比（1.28±0.14）］、LN［（3.09±0.30）比（2.39±0.26）比（1.52±0.25），（2.46±0.24）比（1.87±0.20）比（1.37±0.16）］、PC Ⅰ［（2.93±0.28）比（1.82±0.24）比（1.28±0.20），（2.08±0.28）比（1.76±0.24）比（1.29±0.13）］、PC Ⅲ［（3.21±0.25）比（2.19±0.28）比（1.47±0.24），（2.87±0.20）比（2.09±0.19）比（1.21±0.11）］mRNA及蛋白表达明显降低，差异均有统计学意义（均P<0.05）。结论　高剂量甘草酸二胺可缓解肝纤维化，抑制PCR、TGF-β表达是介导这一改善作用的可能分子机制。

关键词: 慢性肝炎性纤维化, 甘草酸二胺, C反应蛋白, 转化生长因子β