| 引用本文: |
闫盼悦, 苏思远, 叶苗青, 刘皎皎, 杨跃青, 何瑾瑜.化瘀疏肝汤对猪血清诱导肝纤维化大鼠模型保护作用研究[J].湖南中医药大学学报,2026,46(2):232-239[点击复制] |
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| 化瘀疏肝汤对猪血清诱导肝纤维化大鼠模型保护作用研究 |
| 闫盼悦,苏思远,叶苗青,刘皎皎,杨跃青,何瑾瑜 |
| (陕西中医药大学第一临床医学院, 陕西 咸阳 712046;陕西省中医医院肝病科, 陕西 西安 710003) |
| 摘要: |
| 目的 探讨化瘀疏肝汤对猪血清诱导肝纤维化大鼠模型的保护作用。方法 选取80只SD大鼠，随机分成对照组、模型组、阳性组及化瘀疏肝汤低、中、高剂量组，每组13只（有2只验证造模成功）。除对照组外，其余大鼠连续8周，每周2次腹腔注射猪血清0.5 mL/只造模。对照组和模型组给予去离子水，阳性组给予复方鳖甲软肝片0.8 g/（kg·d），化瘀疏肝汤低、中、高剂量组分别给予化瘀疏肝汤30、60、120 g/（kg·d）灌胃给药，每天1次，连续3周。处死大鼠后，检测大鼠血清酶指标丙氨酸氨基转氨酶（ALT）、天冬氨酸氨基转氨酶（AST）、碱性磷酸酶（ALP）、γ-谷氨酰氨基转移酶（GGT）含量。计算肝、脾和胸腺脏器指数，并检测肝组织中羟脯氨酸（hyp）含量。HE染色观察肝脏组织纤维化程度并进行评分。流式细胞术检测外周血样中T淋巴细胞亚群表达以反映免疫功能变化。采用Western blot检测肝组织中母系抗双调蛋白7（Smad7）与平滑肌肌动蛋白（α-SMA）蛋白表达水平。结果 与对照组相比，模型组大鼠胸腺指数降低（P<0.05）；ALT、AST、GGT、ALP含量升高（P<0.05）；hyp含量升高（P<0.01）；肝组织病理评分及纤维化水平升高（P<0.01）；T淋巴细胞亚群中CD3+T淋巴比例、CD3+CD4+T淋巴细胞比例及免疫指数CD3+CD4+/CD3+CD8+比值均下降（P<0.05）；Smad7蛋白表达显著下降而α-SMA表达上升（P<0.05）。与模型组相比，化瘀疏肝汤低、中、高剂量组及阳性胸腺指数升高（P<0.05）；化瘀疏肝汤中、高剂量组及阳性组ALT、AST、GGT、ALP含量降低（P<0.05）；化瘀疏肝汤中、高剂量组及阳性组hyp含量降低（P<0.05，P<0.01）；根据HE染色观察肝脏组织纤维化程度并进行评分，与模型组比较，高剂量组及阳性组肝纤维化评分降低（P<0.01，P<0.05）；化瘀疏肝汤低、中、高剂量组及阳性组T淋巴细胞亚群中CD3+T淋巴比例、CD3+CD4+T淋巴细胞比例及免疫指数CD3+CD4+/CD3+CD8+比值升高（P<0.05，P<0.01）；Smad7蛋白表达上升而α-SMA蛋白表达下降（P<0.05，P<0.01）。结论 化瘀疏肝汤可改善猪血清所致肝纤维化模型大鼠肝功能指标、肝脏组织hyp含量以及肝纤维化水平，并具有提高免疫作用的趋势。其作用机制可能与上调Smad7、抑制α-SMA表达相关，提示化瘀疏肝汤对肝纤维化治疗具有显著作用。 |
| 关键词: 肝纤维化 化瘀疏肝汤 猪血清 复方鳖甲软肝片 胸腺指数 |
| DOI：10.3969/j.issn.1674-070X.2026.02.003 |
| 投稿时间：2025-11-18 |
| 基金项目:国家中医优势专科建设项目(国中医药医政函[2024]90号);陕西省自然科学基金(一般面上项目)(2022JM-519);陕西省高水平中医药重点学科建设项目(SXZYYZDXK-2024005);陕西省感染性疾病临床医学研究中心(中西医结合)(2024S-LCZX-18,2020LCZX-02)。 |
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| Protective effects of Huayu Shugan Decoction on a rat model with hepatic fibrosis induced by porcine serum |
| YAN Panyue, SU Siyuan, YE Miaoqing, LIU Jiaojiao, YANG Yueqing, HE Jinyu |
| (The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China;Department of Hepatology, Shaanxi Provincial Hospital of Chinese Medicine, Xi'an, Shaanxi 710003, China) |
| Abstract: |
| Objective To investigate the protective effects of Huayu Shugan Decoction (HYSGD) on a rat model with hepatic fibrosis (HF) induced by porcine serum (PS). Methods Eighty SD rats were enrolled and randomly divided into control group, model group, positive control group, and low-, medium-, and high-dose HYSGD groups, with 13 rats in each group (with two additional rats used to verify successful modeling). Except for the control group, all rats were intraperitoneally injected with PS (0.5 mL/rat), twice a week for 8 consecutive weeks to establish the model. The control and model groups were given deionized water; the positive control group was given Fufang Biejia Ruangan Tablets (FFBJRGT)[0.8 g/(kg·d)]; and the low-, medium-, and high-dose HYSGD groups were treated with HYSGD by intragastric administration at doses of 30, 60, and 120 g/(kg·d), respectively, once daily for 3 consecutive weeks. After the rats were sacrificed, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were mea-sured. Organ indices of liver, spleen, and thymus were calculated, and hydroxyproline (Hyp) content in liver tissues was checked. HE staining was performed to observe and evaluate the degree of HF. Flow cytometry was used to assess the expression of T lymphocyte subsets in peripheral blood samples as indicators of changes in immune function. Western blot was employed to determine the protein expression levels of SMAD family member 7 (Smad7) and α-smooth muscle actin (α-SMA) in liver tissues. Results Compared with the control group, the model group showed a decreased thymus index (P<0.05), elevated content of ALT, AST, GGT, and ALP (P<0.05), increased Hyp content (P<0.05), and higher pathological score and fibrosis level in liver tissues (P<0.01). Moreover, the proportions of CD3+ T and CD3+CD4+ T lymphocytes, along with the immune index (CD3+CD4+/CD3+CD8+ ratio), were all reduced (P<0.05). At the protein level, Smad7 protein expression was significantly downregulated, while α-SMA expression was upregulated (P<0.05). Compared with the model group, the low-, medium-, and high-dose HYSGD groups and positive control group exhibited an increase in thymus index (P<0.05), the medium- and high-dose HYSGD groups and positive group showed decreased levels of ALT, AST, GGT, and ALP (P<0.05) and reduced Hyp level (P<0.05, P<0.01). Compared with the model group, the fibrosis scores were significantly reduced in the high-dose HYSGD and positive control groups (P<0.01, P<0.05). Furthermore, the low-, medium-, and high-dose HYSGD groups and positive control group demonstrated elevated proportions of CD3+ T and CD3+CD4+ T lymphocytes, along with the immune index (CD3+CD4+/CD3+CD8+ ratio) (P<0.05, P<0.01). Additionally, Smad7 protein expression increased, whereas α-SMA protein expression decreased (P<0.05, P<0.01). Conclusion HYSGD can significantly improve hepatic function indices, hepatic Hyp content, and HF level in rat models with PS-induced HF, accompanied by a trend toward enhanced immune function. Its mechanism of action may be related to the upregulation of Smad7 expression and the inhibition of α-SMA expression, suggesting that HYSGD has a significant therapeutic effect on HF. |
| Key words: hepatic fibrosis Huayu Shugan Decoction porcine serum Fufang Biejia Ruangan Tablets thymus index |
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