Liu X, Meng J L, Wang M G, Mao D W, Dai M
Hunan University of Traditional Chinese Medicine, Changsha 410208, China.
Guangxi University of Traditional Chinese Medicine, Nanning 530200, China.
Zhonghua Gan Zang Bing Za Zhi. 2024 Apr 20;32(4):354-362. doi: 10.3760/cma.j.cn501113-20230816-00060.
To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1β content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1β, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1β and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1β, IL-18 protein, and mRNA (<0.01) were all significantly increased in the model than the blank group (<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1β, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (<0.01). Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.
观察升散解毒化瘀方对急性-on-慢性肝衰竭（ACLF）大鼠炎症性肝损伤的治疗作用及其对NLRP3信号通路激活强度的影响。63只SD大鼠随机分为空白组、模型组、升散解毒化瘀方低、中、高剂量组（7.29 g/kg/d、14.58 g/kg/d、29.16 g/kg/d）。采用四氯化碳联合d-半乳糖胺和脂多糖复制ACLF大鼠模型。使用不同剂量梯度的升散解毒化瘀方进行为期5天的干预治疗，然后采集大鼠血清和组织样本。用生化分析仪检测大鼠血清ALT、AST和TBIL水平。用ELISA检测血清IL-18和IL-1β含量。用HE染色观察肝组织的组织形态学变化。用免疫组化检测肝组织中GSDMD的表达。用Western blot和PCR检测NLRP3、Caspase1、ASC、TLR4、IL-1β、IL-18蛋白及mRNA表达水平。采用方差分析和秩和检验进行组间比较。与空白组相比，模型组大鼠肝组织严重受损。模型组大鼠血清ALT、AST、TBIL水平、炎症因子IL-1β和IL-18以及GSDMD蛋白表达水平、NLRP3表达水平、TLR4、caspase 1、ASC、IL-1β、IL-18蛋白及mRNA均显著高于空白组（<0.01）。此外，与模型组相比，升散解毒化瘀方低、中、高剂量组可改善ACLF大鼠肝组织损伤，升散解毒化瘀方不同剂量梯度组大鼠血清ALT、AST、TBIL、IL-1β、IL-18水平及肝组织GSDMD蛋白、NLRP3、TLR4、caspase 1、ASC表达均低于模型组，高剂量组降低最为明显（<0.01）。升散解毒化瘀方可减弱NLRP3信号通路的激活强度，减轻肝组织病理损伤，减少炎症因子释放，减轻ACLF大鼠炎症性肝损伤。
