甘草素抑制HMGB1的表达缓解造血干细胞移植后肝损伤

doi:10.3969/j.issn.1006-6233.2021.10.002

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Abstract Objective: To explore the effect interaction of glycyrrhizin regulating and HMGB1 on liver injury after hematopoietic stem cell transplantation. Methods: C57BL/6 mice were selected served as the donor mices, and while BALB/C mice were the recipients. According to the initial body weight, The recipients were randomly divided into the control group, the model group and the glycyrrhizin treatment group (8 mice in each group) according to their initial body weight, with 8 in each group. Mice in the control group was were fed normallyas usual, and while mice in the model group and glycyrrhizin treatment group were operated to establish liver injury models after hematopoietic stem cell transplantationused for the establishment of hematopoietic stem cell transplantation-induced liver injury model. Mice in the glycyrrhizin treatment group were given glycyrrhizin gavage (40 mg·kg^-1·d^-1) for 14 days. Mice in control group and model group were given the same dose of saline. On the 15th day after transplantation, mice were sacrificed, and whole blood and liver tissues were collected. The levels of plasma HMGB1, AST, ALT, and TBIL content was were detected by ELISA, . Immunohistochemistry and RT-PCR were used to determine the level or mRNA expression of HMGB1 inthe expression of HMGB1 in liver tissue was observed by immunohistochemistry, the expression level of HMGB1 mRNA in liver tissue was detected by RT-PCRs of mice, respectively. ALT, AST and TBILcontent and inflammatory factors in liver tissue were determined by ELISA, and HE staining was used to observe the pathology of liver tissues, and explore the relationship between HMGB1 and liver injury after hematopoietic stem cell transplantation. Results: The liver function test found demonstrated that after hematopoietic stem cell transplantation, the levels of plasma ALT, AST and TBIL values of mice were significantly increased compared to the control group (P<0.01). After glycyrrhizin treatment, Glycyrrhizin treatment remarkably reduced the levels of these indexes (P<0.05). the plasma ALT level and AST level were significantly lower than that of the model group (P<0.01), TBIL was lower than the model group (P<0.05). Based on HE staining, the model group showed The results of HE staining showed that the normal structure of the liver damaged hepatic lobuless was were damaged after transplantation, the disordered arrangement of liver cells was disordered, vacuoles appeared in the cytoplasm, nuclei constricted and even necrotic, and inflammatory cell infiltration appeared. After gGlycyrrhizin gavage treatment attenuated the liver injury caused by hematopoietic stem cell transplantation, the liver tissue pathological changes were significantly improved. The results of the detection of inflammatory factors in liver tissue indicatedIn addition, we further found that: compared with the control group, the levels of TNF-α, IL-6, and IL-1β in the liver tissue of the model group were significantly increased (P<0.01). As expected, IL after treatment with glycyrrhizin reduced Tthe levels of TNF-α, and IL-6, and were significantly reduced (P<0.01), and the level of IL-1β was reduced (P<0.05). The detection of the expression level of HMGB1 showed that tThe level of HMGB1 in the plasma and liver tissues of the model group mice was significantly increased (P<0.01), and was significantly decreased after treatment with glycyrrhizin (P<0.01). The mRNA expression of HMGB1 obtained the similar patterns. the expression of HMGB1 mRNA in the liver tissue was also Show the same tren The plasma levels of ALT, AST and , TBIL, levels IL-1β, IL-6, and TNF-α of in mice in of the anti-HMGB1 group were significantly lower than those in the model group (P<0.01), while HMGB1 treatment significantly reversed the inhibitory effect of glycyrrhizin on the levels of ALT, AST and TBILthese indexes (P<0.05). The expression of IL-1β, IL-6 and TNF-α in liver tissues of mice in the anti-HMGB1 group was significantly lower than that in the model group (P<0.01), while HMGB1 treatment significantly reversed the inhibitory effect of glycyrrhizin on the expression of IL-1β, IL-6 and TNF-α ( P<0.01). Conclusion: HMGB1 has a promoting effect on liver injury after hematopoietic stem cell transplantation. Glycyrrhizin can alleviate liver injury after hematopoietic stem cell transplantation by inhibiting the expression of HMGB1, providing new ideas for the clinical treatment of liver injury after hematopoietic stem cell transplantation.

Key words： Hematopoietic stem cell transplantation Liver damage HMGB1 Glycyrrhizin

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2021.10.002 OR http://www.hbyxzzs.cn/EN/Y2021/V27/I10/1592

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