| 李静,张翠丽,霍瑞静.芍药苷对 HBV感染引起小鼠肝组织损伤的保护作用及机制探讨[J].安徽医药,2025,29(1):39-43. |
| 芍药苷对 HBV感染引起小鼠肝组织损伤的保护作用及机制探讨 |
| Study on the protective effect and mechanism of paeoniflorin on liver tissue damage caused in HBV-infected mice |
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| DOI：10.3969/j.issn.1009-6469.2025.01.007 |
| 中文关键词: 芍药苷 乙型肝炎，慢性 乙型肝炎病毒感染 炎症反应 细胞焦亡 |
| 英文关键词: Paeoniflorin Hepatitis B,chronic HBV infection Inflammation Pyroptosis |
| 基金项目:河北省中医药管理局科研计划项目( 2020288) |
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| 中文摘要: |
| 目的探讨芍药苷( PF)对乙型肝炎病毒( HBV)感染引起的肝组织损伤的作用及机制。方法 2022年 6月至 2023年 1月，将 40只 C57BL/6小鼠按随机数字表法分为假手术(Sham)组、 HBV组、 5 mg/kg PF组和 10 mg/kg PF组，每组 10只。除对照组外，其余各组小鼠通过尾静脉注射重组腺病毒载体构建 AAV8-1.3HBV感染模型。于造模前 24 h至造模后 5周，每日为小鼠灌胃给予不同剂量的 PF溶液或等体积溶剂。随后，采用生化分析法检测小鼠血清天冬氨酸转氨酶( AST)和丙氨酸转氨酶(ALT)水平；酶联免疫吸附测定( ELISA)检测小鼠血清乙型肝炎 e抗原( HBeAg)和乙型肝炎表面抗原( HbsAg)水平；苏木精 -伊红(HE)染色检测小鼠肝组织病理变化； Masson染色检测肝组织纤维化情况； ELISA检测小鼠肝组织乳酸脱氢酶( LDH)、白细胞介素 -1β(IL-1β)和白细胞介素 -18(IL-18)水平；原位末端转移酶标记法( TUNEL)检测小鼠肝组织细胞凋亡情况；蛋白质印迹法检测小鼠肝组织焦亡相关蛋白核因子 -κB(NF-κB)、 Nod样受体蛋白 3(NLRP3)及焦孔素 D(GSDMD)的表达。结果 Sham组血清 AST(44.89±7.82)U/L、ALT为( 43.13±5.72)U/L，HBeAg和 HbsAg无表达， HBV组 AST、ALT、HBeAg和 HbsAg分别为( 98.76±12.21)U/L、(75.38±1.23)U/L、(52.22±7.15)U/L、(67.33±9.25)U/L，HBV组小鼠各指标显著升高( P<0.05)；与 Sham组比较， HBV组肝组织内细胞形态发生明显改变，炎性细胞浸润明显，出现大量肝纤维化； HBV组肝组织 LDH、IL-1β、IL-18显著高于 Sham组( P<0.05)HBV组细胞凋亡明显增加， HBV组 NF-κB、NLRP3、GSDMD表达，显著高于 Sham组( P<0.05)。与 HBV组比较， 5 mg/kg PF组10 mg/kg PF组小鼠血清 AST、ALT、HBeAg和 HbsAg水平显著降低( P<0.05)；肝组织病理损伤明显减轻，肝纤维化程度改善；肝组织 LDH、IL-1β及 IL-18水平显著降低，细胞凋亡明显降低， NF-κB、NLRP3及 GSDMD蛋白表达显著下调(均 P <0.05)5 mg/kg PF组和 10 mg/kg PF组之间差异有统计学意义( P<0.05)。结论 PF可通过调控 NLRP3介导的细胞焦亡减轻 和，HBV感染，引起的肝组织损伤， PF对 HBV感染引起小鼠肝组织损伤有保护作用。 |
| 英文摘要: |
| Objective To investigate the role and its mechanism of paeoniflorin (PF) on liver tissue injury in HBV-infected mice. Methods From June 2022 to January 2023, 40 C57BL/6 mice were divided into Sham group, HBV group, 5 mg/kg PF group and 10mg/kg PF group by randomization, with 10 mice in each group. Except for the control group, the mice in the other groups were injectedwith recombinant adenovirus vector through tail vein to establish an AAV8-1.3 HBV infection model rat. From 24 hours before model-ing to 5 weeks after modeling, mice were given different doses of PF solution or equal volume solvent by gavage every day. Subsequent-ly, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of mice were detected by biochemicalanalysis. The levels of HBV serum markers (HBeAg) and hepatitis B surface antigen (HbsAg) were detected in serum by enzyme-linked immunosorbent (ELISA) assay. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of liver tissue. Massonstaining was used to detect the fibrosis of liver; the levels of lactate dehydrogenase (LDH), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in liver tissue of mice were detected by ELISA assay. The apoptosis of liver cells in mice was detected by terminal deoxynucleo-tidyl transferase-mediated dUTP nick end labeling (TUNEL) method. Western blotting was used to detect the pyroptosis-related protein expression of nuclear factor-κB (NF-κB)NF-κB, nod-like receptor protein 3 (NLRP3), and gasdermins D (GSDMD) in liver. Results Serum AST (44.89±7.82)U/L, ALT (43.13±5.72)U/L, HBeAg and HbsAg were not expressed in Sham group. The values of AST, ALT,HBeAg and HbsAg in HBV group were (98.76±12.21)U/L, (75.38±1.23)U/L, (52.22±7.15)U/L and (67.33±9.25)U/L, respectively,which were significantly increased in HBV group (P<0.05). Compared with Sham group, the morphology of liver cells in HBV group wassignificantly changed, inflammatory cell infiltration was obvious, and a large number of liver fibrosis appeared. LDH, IL-1β and IL-18 in HBV group, were significantly higher than those in HBV group. Cell apoptosis in HBV group was increased than those in Shamgroup, and the expression of NF-κB ,NLRP3, GSDMD in HBV group were significantly higher than those in Sham group (P<0.05). Com-pared with HBV group, the levels of AST, ALT, HBeAg and HbsAg in serum of 5 mg/kg PF group and the 10 mg/kg PF group were sig-nificantly decreased (P <0.05). The pathological damage of liver tissue was significantly alleviated, and the degree of liver fibrosis wasimproved. The levels of LDH, IL-1β and IL-18 in liver tissue were significantly decreased, the cell apoptosis was markedly decreased, and the pyroptosis-related protein expression of NF-κB, NLRP3 and GSDMD was significantly down-regulated (all P <0.05), and these differences between 5 mg/kg PF group and 10 mg/kg PF group were statistically significant (P <0.05).Conclusion PF alleviates liver tissue injury caused by HBV infection by regulating NLRP3-mediated pyroptosis, and PF has a protective effect on liver tissue damage caused by HBV infection in mice. |
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