Ameliorative effects of Qingganjiuwei powder, a traditional Mongolian medicine, against CCl4-induced liver fibrosis in rats
Ameliorative effects of Qingganjiuwei powder, a traditional Mongolian medicine, against CCl4-induced liver fibrosis in rats
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蒙药清肝九味散对四氯化碳所致大鼠肝纤维化的改善作用
DOI：
10.1016/j.jep.2020.113226
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发表时间：
2021-01-10
影响因子：
5.4
通讯作者：
Li, Yuxin
中科院分区：
文献类型：
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作者：
Ge, Hongyan;Wang, Anqing;Li, Yuxin
民族药理学相关性：清肝九味散（QGJWS）是著名的传统药物，含有九种药材。该药在内蒙古地区常用，具有显着的临床保肝作用。研究目的：探讨清肝健脾方是否具有抑制大鼠肝纤维化的作用，并揭示其潜在机制。方法：采用CC14诱导SD大鼠肝纤维化模型8周。接下来，给大鼠灌胃定量剂量的 QGJWS（每天 0.525、1.575、4.725 g/kg）或水飞蓟素（SIL；每天 120 mg/kg），持续 8 周。随后处死大鼠，检测血清转氨酶（ALT、AST）水平，组织病理学变化，以及基质金属蛋白酶2（MMP2）、MMP9、金属蛋白酶组织抑制剂（TIMP1）、I型胶原（COL1）、α-平滑肌肌动蛋白（α-SMA）的mRNA和蛋白表达量，并结合细胞外信号调节激酶（ERK）、C-Jun的磷酸化水平。分别测定各组肝组织中氨基末端激酶（JNKs）和应激激活蛋白激酶2（p38）蛋白的含量。结果：模型大鼠的症状、体征符合肝纤维化的诊断标准。相比之下，QGJWS治疗明显改善了大鼠的一般状况。此外，组织病理学分析表明，QGJWS治疗组的肝脏形态和结构得到改善，肝细胞坏死、淋巴细胞浸润和假小叶减少，从而有助于降低METAVIR评分。 QGJWS 给药还显着降低血清 ALT 和 AST 水平。进一步的免疫组织化学、蛋白质印迹和实时PCR分析表明，QGJWS显着增强MMP2、MMP9的mRNA和蛋白表达，并下调COL1、TIMP1和α-SMA的表达水平。此外，QGJWS通过抑制ERK、JNKs和p38蛋白的磷酸化，降低肝脏丝裂原激活蛋白激酶(MAPKs)通路的活性。结论：QGJWS对CC14诱导的大鼠肝纤维化具有显着的保护作用，这可能是由于其抑制MAPKs信号通路的能力。
Ethnopharmacological relevance: Qingganjiuwei powder (QGJWS) is a well-known traditional drug containing nine kinds of medicinal materials. This drug is commonly used in the Inner Mongolia region and exerts remarkable clinical effects on hepatic protection.Aim of the study: To investigate whether QGJWS inhibits liver fibrosis in rats and to reveal its potential mechanisms.Methods: Liver fibrosis model was induced by CC14 for 8 weeks in SD rats. Next, rats were intragastrically administered quantum satis doses of QGJWS (0.525, 1.575, 4.725 g/kg per day) or Silymarin (SIL; 120 mg/kg per day) for 8 weeks. Afterwards, the rats were sacrificed, and serum aminotransferase (ALT and AST) levels, histopathological changes as well as the mRNA and protein expression of matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinasel (TIMP1), collagen type I(COL1), alpha-smooth muscle actin (alpha-SMA), combined with phosphorylation levels of extracellular signal-regulated kinase (ERK), C-Jun amino-terminal kinases (JNKs) and stress-activated protein kinase-2 (p38) protein in liver tissues were measured in each groups, respectively.Results: The symptoms and signs of the model rats were consistent with the diagnostic criteria of liver fibrosis. By contrast, treatment with QGJWS clearly improved the general condition of rats. Also, the morphology and structure of liver can be ameliorated, there are fewer hepatocyte necrosis and lymphocytic infiltration and pseudolobuli in QGJWS treatment groups as demonstrated by histopathological analysis, thus helping bring about lower METAVIR scores. QGJWS administration also dramatically decreased serum ALT and AST levels. Further immunohistochemistry, western blotting and Real-Time PCR analysis revealed that QGJWS significantly enhanced the mRNA and protein expression of MMP2, MMP9, and downregulated the expression levels of COL1, TIMP1 and alpha-SMA. Furthermore, QGJWS reduced the activities of mitogen-activated protein kinases (MAPKs) pathway in liver by inhibited the phosphorylation of ERK, JNKs and p38 proteins.Conclusions: QGJWS offers notable protection against CC14-induced liver fibrosis in rats, which may be due to its ability to inhibited the MAPKs signaling pathway.