ABSTRACT
ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl4-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl4 olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl4 induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.
ABSTRACT
Hepatic fibrosis (HF) is a self-healing pathological process after all kinds of chronic liver injuries and can cause diseases such as liver cirrhosis and liver cancer. The Wnt signaling pathway is highly conserved in species evolution and widely exists in invertebrates and vertebrates, and many studies have confirmed that the Wnt signaling pathway is closely associated with the development and progression of HF. This article reviews the mechanisms of the classical and non-classical Wnt signaling pathways in regulating hepatic stellate cells, hepatic macrophages, and hepatic progenitor cells, so as to provide new ideas for subsequent studies on the mechanism of the Wnt signaling pathway in regulating HF and further exploration of therapeutic targets that can reverse HF.
ABSTRACT
BACKGROUND: Schwann calls are seed cells for constructing tissue engineered peripheral nerves. But their in vitro isolation, culture and purification are difficult. Acellular nerve allografts (ANA) have a great effect on repairing peripheral nerve defects, and it can induce marrow stromal cells (MSCs) into Schwann-like calls. Accordingly, MSCs can be used as seed calls theoretically in constructing tissue engineered peripheral nerves, instead of Schwann cells OBJECTIVE: To observe the repairing effect of tissue engineered peripheral nerves constructed with MSCs on sciatic nerve defects and to assess the feasibility of repairing peripheral nerve defects with MSCs as seed calls. DESIGN, TIME AND SE'I-rlNG: A randomized control animal experiment was conducted in the laboratory of Basic Medicine Collage of Dali Collage from July to December in 2008.MATERIALS: A total of 30 SD rats were divided randomly into 3 groups, with 10 in each group. In MSCs+ ANA group, end-to-end anastomosis were performed with 10/0 non traumatic suture to broken ends of rat sciatic nerves and tissue engineered nerves cultured using MSCs combined with ANA; In ANA group, ANA were bridged to broken ends of sciatic nerves; In METHODS: The 10ram sciatic nerve defects in rats were repaired using MSCs-constructed tissue engineered peripheral nerves, whose repairing effects were evaluated at week 12 post transplant through sciatic function index (SFI), gastrocnemius wet weight recovery rate, S-100 immunohistochemical staining and electron microscope observation, etc. MAIN OUTCOME MEASURES: Morphological changes of calls were observed during the culture of compounds; SFI and gastrocnemius wet weight recovery rates were detected after transplantation; New myelinization, axon growth and nerve fiber distdbuUon were observed with toluidine blue staining; Schwann calls growth and nerve fiber regeneration were observed with transmission electron microscope combined with S-100 protein immunohistochemical staining method.RESULTS: The detection results showed that SFI and gastrocnemius wet weight recovery rate were higher in the MSCs+ ANA group than in the ANA group (P < 0.05). Compared the ANA group, the MSCs+ ANA group had more S-100 proteins expressed in its compounds obviously, and the number, the diameter of its myelinated nerve fibers as well as its myelin sheath thickness were all greater than those of the ANA group (P < 0.05). The repairing effect of the MSCs+ ANA group was close to that of the autotransplantation group.CONCLUSION: MSCs-constructed tissue engineered nerves have a better effect on repairing peripheral nerve defects than ANA, and MSCs as seed cells have a high value in peripheral nerve tissue engineering.