Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Acupunct Med. 2012 Dec;30(4):324-30. doi: 10.1136/acupmed-2012-010167. Epub 2012 Jul 4.
Acupuncture treatment has been increasingly used to treat chronic liver diseases. We previously reported that acupuncture combined with curcumin, a natural antifibrotic compound, could remarkably attenuate liver fibrosis in chemically intoxicated rats, but the underlying molecular mechanisms are poorly understood. The present study was aimed at investigating the effects of acupuncture combined with curcumin on platelet-derived growth factor (PDGF) signalling and extracellular matrix (ECM) regulation in the fibrotic liver.
A total of 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination treatment groups. During the establishment of fibrosis using carbon tetrachloride (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, serum PDGF levels were measured. Protein and mRNA expression of key effectors in PDGF pathway and fibrinolysis in the liver was determined.
Acupuncture combined with curcumin potently reduced serum PDGF levels and selectively disrupted the PDGF-βR/extracellular signal-regulated kinase (ERK) cascade. Combination treatment also significantly repressed expression of connective tissue growth factor and upregulated expression of matrix metalloproteinase-9, promoting fibrinolysis in the fibrotic liver.
The beneficial effects of acupuncture and its combination with curcumin could be attributed to the disruption of PDGF-βR/ERK pathway and stimulated ECM degradation in the fibrotic liver. Acupuncture treatment significantly enhanced curcumin effects at the molecular level. These findings may provide molecular insights into the potential of acupuncture combined with curcumin for prevention of hepatic fibrosis.
针刺疗法已越来越多地用于治疗慢性肝病。我们之前报道过，针刺联合天然抗纤维化化合物姜黄素可显著减轻化学中毒大鼠的肝纤维化，但具体的分子机制尚不清楚。本研究旨在探讨针刺联合姜黄素对肝纤维化中血小板衍生生长因子（PDGF）信号和细胞外基质（ECM）调节的影响。
将 60 只雄性 Sprague-Dawley 大鼠随机分为对照组、模型组、假手术组、针刺组、姜黄素组和联合治疗组。在使用四氯化碳（CCl4）建立纤维化的过程中，同时进行 LR3、LR14、BL18 和 ST36 针刺和/或姜黄素口服治疗。治疗后，检测血清 PDGF 水平。测定肝内 PDGF 通路关键效应物和纤维溶解的蛋白和 mRNA 表达。
针刺联合姜黄素可显著降低血清 PDGF 水平，并选择性破坏 PDGF-βR/细胞外信号调节激酶（ERK）级联反应。联合治疗还显著抑制结缔组织生长因子的表达，上调基质金属蛋白酶-9 的表达，促进纤维溶解在纤维化的肝脏。
针刺及其与姜黄素联合应用的有益作用可能归因于破坏 PDGF-βR/ERK 途径和刺激 ECM 在纤维化肝脏中的降解。针刺治疗在分子水平上显著增强了姜黄素的作用。这些发现可能为针刺联合姜黄素预防肝纤维化的潜力提供分子见解。
