慈菇消脂方通过抑制Hedgehog信号通路激活缓解非酒精性脂肪性肝炎肝纤维化

Cigu Xiaozhi Prescription Alleviates NASH Liver Fibrosis by Inhibiting the Activation of the Hedgehog Signaling Pathway

  • 摘要:
    目的 探究慈菇消脂方(Cigu Xiaozhi Prescription, CGXP)治疗非酒精性脂肪性肝炎(Non-Alcoholic steatohepatitis, NASH)肝纤维化的潜在机制。
    方法 建立了NASH小鼠模型,并通过计算肝脏指数来评估肝脏肿大程度,同时利用HE和Masson染色法观察肝纤维化程度。此外,免疫组化法检测肝纤维化相关蛋白α-SMA、Collagen 1、MMP2和MMP9蛋白表达情况。通过Western blot和qPCR技术检测小鼠肝脏中HIF-1α、E-cadherin、N-cadherin、Shh、Smo、Gli1和Gli2的表达水平,并使用碱水法测定了肝脏羟脯氨酸(Hyp)含量。
    结果 高剂量的CGXP能够有效降低肝脏指数(P < 0.001),减轻肝脏肿大和炎症,显著改善肝纤维化小鼠的肝组织病理损伤。CGXP显著降低了肝纤维化相关蛋白α-SMA、Collagen 1、MMP2和MMP9蛋白表达水平(P < 0.01,P < 0.000 1);降低HIF-1α、E-cadherin、N-cadherin、Shh、Smo、Gli1和Gli2的水平,其中高剂量CGXP的治疗效果尤为显著(P < 0.05,P < 0.01,P < 0.001,P < 0.000 1)。
    结论 CGXP可能通过抑制Hedgehog信号通路改变了肝星状细胞(Hepatic stellate cells, HSCs)的活化与增殖,减少了细胞外基质的合成与沉积,缓解NASH小鼠肝纤维化。

     

    Abstract:
    OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription (CGXP) in the treatment of non-alcoholic steatohepatitis (NASH) liver fibrosis.
    METHODS A NASH mouse model was established. The degree of liver enlargement was evaluated by calculating the liver index. Hematoxylin - eosin (HE) and Masson staining were used to observe the degree of liver fibrosis. In addition, immunohistochemistry was employed to detect the expression of liver fibrosis - related proteins, including α - SMA, Collagen 1, MMP2, and MMP9. Western blot and qPCR techniques were used to detect the expression levels of HIF - 1α, E-cadherin, N-cadherin, Shh, Smo, Gli1, and Gli2 in the mouse liver. The alkaline hydrolysis method was used to measure the content of liver hydroxyproline.
    RESULTS CGXP could effectively reduce the liver index (P < 0.001), alleviate liver enlargement and inflammation, and significantly improve the pathological damage of liver tissue in mice with liver fibrosis. CGXP significantly decreased the expression levels of liver fibrosis-related proteins α-SMA, Collagen 1, MMP2 and MMP9 (P < 0.01, P < 0.000 1); reduced the levels of HIF - 1α, E - cadherin, N - cadherin, Shh, Smo, Gli1, and Gli2, and the therapeutic effect of high - dose CGXP was particularly significant (P < 0.05, P < 0.01, P < 0.001, P < 0.000 1).
    CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index, alleviating inflammation, and improving tissue pathological damage. The mechanism may be related to the inhibition of the Hedgehog signaling pathway, which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and deposition of extracellular matrix.

     

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