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| 金茵利胆胶囊对四氯化碳诱导的肝纤维化大鼠的保护作用 |
| 孔鑫1,曹凡1,陈琳1*,王梅1*,唐志书1,2,宋忠兴1,张德柱3 |
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(1. 陕西省中药资源产业化协同创新中心, 秦药特色资源研究开发国家重点实验室(培育), 陕西省创新药物研究中心, 陕西中医药大学, 咸阳 712083;
2. 中国中医科学院研究生院, 北京 100700;
3. 陕西盘龙药业集团股份有限公司, 商洛 726000
*通信作者) |
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| 摘要: |
| 目的 探讨金茵利胆胶囊（JYLD）对四氯化碳（CCl4）诱导的大鼠肝纤维化的保护作用。方法 将40只SD大鼠随机分为空白对照组、模型组、水飞蓟素（阳性药）组、JYLD低剂量组和JYLD高剂量组，每组8只。除空白对照组外，其余各组大鼠均给予40% CCl4腹腔注射每周2次、连续6周诱导大鼠肝纤维化模型，造模期间水飞蓟素组和JYLD低、高剂量组分别给予0.1 g/kg水飞蓟素、0.6 g/kg JYLD、1.2 g/kg JYLD灌胃，每天1次，连续6周。实验结束后计算大鼠肝脏指数和脾脏指数，采用H-E染色和Masson染色观大鼠肝脏组织的病理变化和纤维化程度，用全自动生化仪检测大鼠血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和总胆汁酸（TBA）的含量，用超氧化物歧化酶检测试剂盒测定大鼠血清抗氧化能力，用ELISA检测试剂盒测定大鼠血清中炎症指标IL-6、IL-1β和TNF-α的水平，用免疫组织化学染色检测大鼠肝组织中α-平滑肌肌动蛋白（α-SMA）的表达情况，用qPCR法检测大鼠肝组织中胶原蛋白（Col）Ⅰ、ColⅢ、ColⅣ、NF-κB、基质金属蛋白酶2（MMP-2）、组织金属蛋白酶抑制剂1（TIMP-1）、TGF-β1 mRNA的相对表达量并计算MMP-2/TIMP-1比值。结果 与模型组比较，JYLD低、高剂量组大鼠的肝脏指数降低（P均＜0.01），血清中ALT、AST和TBA含量下降（P＜0.05，P＜0.01），肝组织纤维化程度改善，血清中SOD活性升高（P均＜0.01），IL-6、IL-1β和TNF-α水平降低（P＜0.05，P＜0.01），α-SMA阳性表达减少（P＜0.05，P＜0.01），肝组织中ColⅠ、ColⅢ、ColⅣ、NF-κB、MMP-2、TIMP-1、TGF-β1 mRNA的相对表达量下降（P＜0.05，P＜0.01），MMP-2/TIMP-1比值降低（P＜0.05，P＜0.01）。结论 JYLD对CCl4诱导的大鼠肝纤维化有保护作用，其作用机制可能与抗炎、减少肝细胞外基质沉积、抑制肝星状细胞活化有关。 |
| 关键词: 金茵利胆胶囊 四氯化碳 肝纤维化 抗炎作用 细胞外基质 肝星状细胞 |
| DOI：10.16781/j.CN31-2187/R.20230107 |
| 投稿时间：2023-03-13修订日期：2023-04-25 |
| 基金项目:陕西省重大科技专项（202190025），陕西省教育厅重点科学研究计划项目（22JY019），陕西高校青年创新团队项目（2023），研究生教育教学改革创新项目（JGCX202313）. |
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| Protective effect of Jinyin Lidan capsule on carbon tetrachloride-induced hepatic fibrosis in rats |
| KONG Xin1,CAO Fan1,CHEN Lin1*,WANG Mei1*,TANG Zhishu1,2,SONG Zhongxing1,ZHANG Dezhu3 |
(1. Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources(Cultivation), Shaanxi Innovative Drug Research Center, Shaanxi University of Chinese Medicine, Xianyang 712083, Shaanxi, China;
2. Graduate School, China Academy of Traditional Chinese Medicine, Beijing 100700, China;
3. Shaanxi Panlong Pharmaceutical Group Co., Ltd, Shangluo 726000, Shaanxi, China
*Corresponding authors) |
| Abstract: |
| Objective To investigate the protective effect of Jinyin Lidan capsule (JYLD) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Methods Totally 40 SD rats were randomly divided into 5 groups: blank group, model group, silymarin (positive drug) group, JYLD low-dose group, and JYLD high-dose group, with 8 rats in each group. Except for the blank group, rats in other groups were given intraperitoneal injection of 40% CCl4 twice a week for 6 weeks to induce rat hepatic fibrosis. Rats in the silymarin group (0.1 g/kg), JYLD low-dose group (0.6 g/kg), and JYLD high-dose group (1.2 g/kg) were continuously gavaged once a day for 6 weeks during the modeling period. Rat liver index and spleen index were calculated after the experiment; hematoxylin-eosin staining and Masson staining were used to observe the pathological changes and fibrosis in rat liver tissue; the contents of alanine transaminase (ALT), aspartate transaminase (AST), and total bile acids (TBA) in rat serum were detected by automatic biochemistry; the antioxidant capacity of rat serum was determined by superoxide dismutase (SOD) assay kit; the levels of inflammation indicators (interleukin［IL］-6, IL-1β, and tumor necrosis factor［TNF］-α) in rat serum were detected by enzyme-linked immunosorbent assay (ELISA); the expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemical staining; and the relative expression of collagen (Col) Ⅰ, Col Ⅲ,Col Ⅳ, nuclear factor κB (NF-κB), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1 (TGF-β1) mRNA in rat liver tissue was determined by quantitative polymerase chain reaction, and MMP-2/TIMP-1 ratio was calculated. Results Compared with the model group, the liver index was decreased in the JYLD low- and high-dose groups (both P＜0.01); the serum ALT, AST, and TBA contents were decreased (P＜0.05, P＜0.01); the degree of hepatic fibrosis was improved, and the SOD activity in serum was increased (both P＜0.01); the levels of IL-6, IL-1β, and TNF-α were decreased (P＜0.05, P＜0.01); the positive expression of α-SMA was decreased (P＜0.05, P＜0.01); the relative expression of Col Ⅰ, Col Ⅲ, Col Ⅳ, NF-κB, MMP-2, TIMP-1, and TGF-β1 mRNA was decreased (P＜0.05,P＜0.01); and the MMP-2/TIMP-1 ratio was decreased (P＜0.05, P＜0.01). Conclusion JYLD has a protective effect on CCl4-induced liver fibrosis in rats, and its mechanism may be related to anti-inflammatory effect, reducing extracellular matrix deposition, and inhibiting hepatic stellate cell activation. |
| Key words: Jinyin Lidan capsule carbon tetrachloride hepatic fibrosis anti-inflammatory extracellular matrix hepatic stellate cells |
