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.

Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor(SGLT2i)canagliflozin and epithelial sodium channel inhibitor amiloride or benzamil in combination on the bone metabolism in the rats with the nephrotic syndrome(NS)induced by doxorubicin.Methods In the 49 male SD rats selected,7 were randomly selected as control group(NG),and 42 were built as adria-mycin-induced nephropathy model by injecting adriamycin through the tail vein,and were randomly di-vided into model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),canagliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 cases in each group.Each medication group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.The 24-hour urinary protein(24 h-UTP)of each group was detected one day before treatment to verify the successful preparation of the model.At 6 weeks after treatment,the 24 h-UTP,urine sodium(UNa),urinary potassium(UK)levels in urine and the albumin(ALB),triglyceride(TG),cholesterol(TC),low density lipoprotein(LDL),serum calcium(SCa),sodium(SNa),potassium(SK),25-hydroxyvitamin D(25-OH-D),alkaline phosphatase(ALP),parathyroid hormone(PTH),procollagen type ⅠN-terminal propeptide(PINP)and beta C-terminal cross-linked telopeptides of type Ⅰ collagen(β-CTX)levels in serum were measured,respectively.Results After successful modeling,the levels of 24 h-UTP,TG,TC,LDL and SCa in the MG group were significantly increased,while the levels of ALB,25-OH-D,ALP,PINP and PTH were significantly decreased(P＜0.05 or P＜0.01).After 6 weeks of drug intervention,the body mass of rats treated with KG alone decreased significantly(P＜0.05).Compared with the MG group,the levels of 24 h-UTP,TC,TG,LDL and SCa were significantly decreased,and the level of ALB was significantly increased in all drug groups when compared to the MG(P＜0.05 or P＜0.01).Compared with the MG group,the levels of 25-OH-D,ALP,PINP and β-CTX in the KA group were significantly increased when compared to the MG(P＜0.05 orP＜0.01).Molding and drug therapy had no impact on levels of UNa,UK,SK and SNa(P＞0.05).Conclusion Calaglizin alone,benzamil alone,amiloride alone and cala-glizin combined with benzamil or amiloride can improve the mass proteinuria,hypoproteinemia and hyperlipidemia in adriamycin-induced NS model rats.The combination of caraglipzin and amiloride has a significant osteogenic or osteoclastic effect,which may play a role in reducing the risk of frac-ture in NS rats by forming a new osteogenic/osteoclastic balance.

Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor(SGLT2i)canagliflozin and epithelial sodium channel inhibitor amiloride or benzamil in combination on the bone metabolism in the rats with the nephrotic syndrome(NS)induced by doxorubicin.Methods In the 49 male SD rats selected,7 were randomly selected as control group(NG),and 42 were built as adria-mycin-induced nephropathy model by injecting adriamycin through the tail vein,and were randomly di-vided into model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),canagliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 cases in each group.Each medication group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.The 24-hour urinary protein(24 h-UTP)of each group was detected one day before treatment to verify the successful preparation of the model.At 6 weeks after treatment,the 24 h-UTP,urine sodium(UNa),urinary potassium(UK)levels in urine and the albumin(ALB),triglyceride(TG),cholesterol(TC),low density lipoprotein(LDL),serum calcium(SCa),sodium(SNa),potassium(SK),25-hydroxyvitamin D(25-OH-D),alkaline phosphatase(ALP),parathyroid hormone(PTH),procollagen type ⅠN-terminal propeptide(PINP)and beta C-terminal cross-linked telopeptides of type Ⅰ collagen(β-CTX)levels in serum were measured,respectively.Results After successful modeling,the levels of 24 h-UTP,TG,TC,LDL and SCa in the MG group were significantly increased,while the levels of ALB,25-OH-D,ALP,PINP and PTH were significantly decreased(P＜0.05 or P＜0.01).After 6 weeks of drug intervention,the body mass of rats treated with KG alone decreased significantly(P＜0.05).Compared with the MG group,the levels of 24 h-UTP,TC,TG,LDL and SCa were significantly decreased,and the level of ALB was significantly increased in all drug groups when compared to the MG(P＜0.05 or P＜0.01).Compared with the MG group,the levels of 25-OH-D,ALP,PINP and β-CTX in the KA group were significantly increased when compared to the MG(P＜0.05 orP＜0.01).Molding and drug therapy had no impact on levels of UNa,UK,SK and SNa(P＞0.05).Conclusion Calaglizin alone,benzamil alone,amiloride alone and cala-glizin combined with benzamil or amiloride can improve the mass proteinuria,hypoproteinemia and hyperlipidemia in adriamycin-induced NS model rats.The combination of caraglipzin and amiloride has a significant osteogenic or osteoclastic effect,which may play a role in reducing the risk of frac-ture in NS rats by forming a new osteogenic/osteoclastic balance.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharides （DOP） in reversing carbon tetrachloride （CCl₄）-induced hepatic fibrosis （HF） in rats via the Notch signaling pathway and evaluate the therapeutic effect of DOP by ultrasound elastography. MethodFifty-six male SD rats were randomized into normal， model， colchicine （1×10^-4 g·kg^-1）， Fuzheng Huayu powder （0.45 g·kg^-1）， and low-， medium-， and high-dose （0.05， 0.1， 0.2 g·kg^-1） DOP groups （n=8）. The rats in the model group and each treatment group were injected subcutaneously with a mixture of CCl₄-olive oil （2∶3） once every 3 days for 10 weeks. After 6 weeks of modelling， the rats were administrated with corresponding drugs once a day for 4 weeks. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe the pathomorphological changes of the liver tissue. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， and total bile acids （TBA）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of hyaluronic acid （HA）， laminin （LN）， type Ⅲ precollagen （PC-Ⅲ）， and type Ⅳ collagen （Col-Ⅳ）. The mRNA and protein levels of α-smooth muscle actin （α-SMA）， Notch1， Jagged1， and Hes1 in the liver tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The Young's modulus （YM） of the rat liver was measured by acoustic radiation force impulse （ARFI） elastography before and after treatment. Then， the correlations of YM with the serum levels of HA， LN， PC-Ⅲ， and Col-Ⅳ and the protein levels of α-SMA and Notch1 signaling pathway-related factors in the liver tissue were analyzed. ResultCompared with the normal group， the model group showed disordered arrangement of liver cell cords， obvious infiltration of inflammatory cells， appearance of a large number of fat vacuoles， and fibrous proliferation， elevated levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum， and up-regulated mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.01）. Compared with the model group， drug interventions alleviated the pseudolobule formation and the collagen deposition in confluent areas. Except that the serum level of ALT in the low-dose DOP group had no significant changes， drug interventions， especially high-dose DOP， lowered the levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum and down-regulated the mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.05， P<0.01）. The results of ARFI and correlation analysis showed that the YM of the liver tissue was increased in the model group （P<0.01） compared with that in the normal group， Compared with the model group， drug interventions decreased YM （P<0.01）. YM was positively correlated with the expression levels of HA， LN， PC-Ⅲ， α-SMA， Notch1， Jagged1， and Hes1s （r=0.754， 0.734， 0.801， 0.885， 0.896， 0.757， and 0.800， respectively， P<0.01）， and it had a moderate correlation with Col-Ⅳ （r=0.688， P<0.01）. ConclusionDOP can reverse HF by down-regulating the Notch1/Jagged1/Hes1 signaling pathway. YM can be used as an indicator in the assessment of the efficacy of DOP against HF.

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.

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.