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ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Acupuncture in Medicine 07/2012; · 1.19 Impact Factor
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ABSTRACT: To observe the effect of acupuncture stimulation of "Taichong" (LR 3), "Qimen" (LR 14), etc. on hepatic platelet-derived growth factor (PDGF) signal pathway activity at the protein and mRNA levels in hepatic fibrosis rats.
Forty-six SD rats were randomly divided into control (10 rats), model (12 rats), acupuncture (12 rats) and non-acupoint (12 rats) groups. Hepatic fibrosis model was established by intraperitoneal injection of mixture solution of 50% CCl4 and olive oil [1:1, 3 times on the 1st week (W), twice/W thereafter for 5 more weeks]. During modeling, acupuncture stimulation of "Taichong" (LR 3), "Qimen" (LR 14), "Ganshu" (BL 18) and "Zusanli" (ST 36) was conducted simultaneously. At the end of the experiments, all the rats were sacrificed for collecting their liver and blood samples, followed by separation of the hepatic stellate cells (HSCs). ELISA, Western blot and Real-time quantitative PCR techniques were used to detect the content of serum PDGF and expression levels of PDGF-beta receptor (PDGF-beta R), extracellular signal-regulated kinase (ERK1/2), c-jun N-terminal kinase (JNK) and P 38 genes and proteins of HSCs, respectively.
Compared to the control group, serum PDGF content, and expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein and P 38 protein of HSCs in the model group were upregulated significantly (P < 0.01, P < 0.05). In comparison with the model group, serum PDGF content, and the expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein of HSCs in the acupuncture group were down-regulated apparently (P < 0.05, P < 0.01). No significant differences were found between the acupuncture and non-acupoint groups in serum PDGF content and between the model group and non-acupoint group in the expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein, JNK protein and P 38 protein of HSCs, as well as between the model group and acupuncture group in the expression levels of JNK protein and P 38 protein of HSCs (P > 0.05).
Acupuncture intervention can effectively down-regulate serum PDGF content, and expression levels of PDGF-beta R mRNA and protein, ERK mRNA and protein of HSCs in liver fibrosis rats, which may contribute to its effect in improving liver fibrosis through down-regulating PDGF signal pathway activity.
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] 04/2012; 37(2):87-92.
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Feng Zhang,
Jin Ma,
Yin Lu,
Guang-Xia Ni,
Chun-Yan Ni,
Xue-Jiao Zhang,
Xiao-Ping Zhang,
De-Song Kong, Ai-Yun Wang,
Wen-Xing Chen,
Shi-Zhong Zheng
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ABSTRACT: Increasingly, studies demonstrate the effectiveness of acupuncture therapy against liver fibrosis. Curcumin is a natural product with antifibrotic effects, but has poor pharmacokinetic profiles. This study aimed to evaluate whether acupuncture combined with curcumin could more potently attenuate liver fibrosis in chemical intoxicated rats.
60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination therapy 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, pathological indexes and histology for hepatic injury and fibrogenesis were detected. The expression of extracellular matrix (ECM) components was also determined.
Acupuncture combined with curcumin potently protected the liver from CCl(4)-induced injury and fibrogenesis, as indicated by reduced levels of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, hyaluronic acid, laminin and procollagen III. Combined use also led to significant liver histological improvements. Furthermore, combined use effectively inhibited ECM expression such as α-smooth muscle actin, fibronectin and α1(1) collagen.
Acupuncture treatment could significantly enhance the antifibrotic efficacy of curcumin on CCl(4)-induced hepatic fibrosis in rats in vivo, suggesting that a combination of acupuncture with curcumin may be exploited for the prevention of hepatic fibrosis.
Acupuncture in Medicine 02/2012; 30(2):132-8. · 1.19 Impact Factor
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ABSTRACT: To investigate the protective effect of acupuncture intervention on liver in carbon tetrachloride induced hepatic fibrosis rats and to reveal its impact on extracellular matrix production in the liver tissue.
A total of 46 SD rats were randomly divided into control group (n = 10), model group (n = 12), sham group (n = 12) and acupuncture group (n = 12). Hepatic fibrosis model was established by intraperitoneal injection of 50% olive oil containing CCl (1 mL/kg), 3 times in the 1st week and twice per week from the 2nd to the 6th week. During the fibrosis model establishment, acupuncture of "Taichong" (LR 3), "Qimen" (LR 14), "Ganshu" (BL 18) and "Zusanli" (ST 36) was carried out simultaneously. In the sham group, non-acupuncture points (0.5 cm left to the above-mentioned real points) were punctured. The treatment was conducted 3 times a week in the first three weeks and then twice a week for the last three weeks. Serum levels of hyaluronic acid (HA), liminin (LN) and precollagen (PC III) were determined by enzyme linked immunosorbent assay for assessing the hepatic fibrosis degree. Primary hepatic stellate cells (HSC) were separated. Western blot assay was used to detect the expression of alpha-smooth muscle actin (SMA), alpha 1 (l) collagen, fibronectin, matrix metalloproteinase (MMP)-9 (components of extracellular matrix, ECM) and tissue inhibitor of metalloprotei-nase-1 (TIMP-1, an inhibitor of MMP-9) proteins of HSC. Real-time quantitative polymerase chain reaction was used to detect the expression levels of alpha-SMA, alpha 1 (1) collagen and fibronectin genes of HSC.
Compared with the control group, contents of serum HA, LN and PC III, expression levels of alpha-SMA, alpha 1 (I) collagen and fibronectin proteins and genes, and TIMP-1 protein of HSC were significantly increased in the model group (P < 0.01, P < 0.05), while MMP-9 protein (an enzyme for degradating ECM) expression level of HSC in the model group was down-regulated significantly (P < 0.01), suggesting a formation of hepatic fibrosis, impairment of the liver tissue fibrosis and imbalance of degradation of ECM. H.E. staining showed an ameliorated liver injury (disorder of hepatocyte arrangement, hepatocyte necrosis, formation of pseudolobule, etc.) in the acupuncture group in comparison with the model group. In comparison with the model group, serum HA and LN contents, expression levels of alpha-SMA, alpha 1(I) collagen and fibronectin proteins, and alpha-SMA mRNA and fibronectin mRNA of HSC were downregulated considerably in the acupuncture group (P < 0.05, P < 0.01). On the contrary, MMP-9 protein expression level of HSC was up-regulated remarkably in the acupuncture group compared with the model group (P < 0.05). No significant changes were found in all the aforementioned indexes in the sham group, and serum PC III content as well as alpha 1 (I) collagen mRNA and TIMP-1 protein expression levels of HSC in the acupuncture group compared with those in the model group (P > 0.05).
Acupuncture treatment can significantly relieve CCl4-induced hepatic fibrosis in hepatic fibrosis rats probably by inhibiting the synthesis and deposite of HA and LN, down-regulating expression levels of alpha-SMA, alpha 1(1) collagen and fibronectin proteins, and alpha-SMA mRNA and fibronectin mRNA of HSC as well as up-regulating MMP-9 protein expression of HSC.
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] 02/2012; 37(1):8-14.
