Phosphodiesterase 4 (PDE4), crucial in regulating the cyclic adenosine monophosphate (cAMP) signaling pathway, significantly impacts liver pathophysiology. This article highlights the comprehensive effects of PDE4 on liver health and disease, and its potential as a therapeutic agent. PDE4's role in degrading cAMP disrupts intracellular signaling, increasing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This contributes to liver inflammation in conditions such as hepatitis and non-alcoholic steatohepatitis (NASH). Additionally, PDE4 is a key factor in liver fibrosis, characterized by excessive extracellular matrix deposition. Inhibiting PDE4 shows promise in reducing liver fibrosis by decreasing the activation of hepatic stellate cells, which is pivotal in fibrogenesis. PDE4 also influences hepatocyte apoptosis a common feature of liver diseases. PDE4 inhibitors protect against hepatocyte apoptosis by raising intracellular cAMP levels, thus activating anti-apoptotic pathways. This suggests potential in targeting PDE4 to prevent hepatocyte loss. Moreover, PDE4 regulates hepatic glucose production and lipid metabolism, essential for liver function. Altering cAMP levels through PDE4 affects enzymes in these metabolic pathways, making PDE4 a target for metabolic disorders like type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Since PDE4 plays a multifaceted role in liver pathophysiology, influencing PDE4's mechanisms in liver diseases could lead to novel therapeutic strategies. Still, extensive research is required to explore the molecular mechanisms and clinical potential of targeting PDE4 in liver pathologies.

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PDE4 在肝脏病理生理学中的调节途径和治疗潜力

磷酸二酯酶 4 (PDE4) 在调节环磷酸腺苷 (cAMP) 信号通路中至关重要，可显着影响肝脏病理生理学。本文重点介绍了 PDE4 对肝脏健康和疾病的综合影响及其作为治疗剂的潜力。 PDE4 降解 cAMP 的作用会破坏细胞内信号传导，增加肿瘤坏死因子-α (TNF-α) 和白细胞介素 6 (IL-6) 等促炎细胞因子。这会导致肝炎和非酒精性脂肪性肝炎 (NASH) 等疾病中的肝脏炎症。此外，PDE4 是肝纤维化的关键因素，其特征是细胞外基质过度沉积。抑制 PDE4 有望通过减少肝星状细胞的活化来减少肝纤维化，肝星状细胞是纤维形成的关键。 PDE4 还影响肝细胞凋亡，这是肝脏疾病的常见特征。 PDE4 抑制剂通过提高细胞内 cAMP 水平来防止肝细胞凋亡，从而激活抗凋亡途径。这表明靶向 PDE4 具有防止肝细胞损失的潜力。此外，PDE4 调节肝脏葡萄糖生成和脂质代谢，这对肝功能至关重要。通过 PDE4 改变 cAMP 水平会影响这些代谢途径中的酶，使 PDE4 成为 2 型糖尿病和非酒精性脂肪肝 (NAFLD) 等代谢性疾病的靶标。由于 PDE4 在肝脏病理生理学中发挥多方面的作用，影响 PDE4 在肝脏疾病中的机制可能会带来新的治疗策略。尽管如此，仍需要进行广泛的研究来探索靶向 PDE4 在肝脏病理学中的分子机制和临床潜力。