AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibro...AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with lie and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 Iobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P〈0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.展开更多
AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with li...AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine(DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin(IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells(KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were cocultured with KCs in vitro to assess the effects of UCMSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UCMSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the coculture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.展开更多
目的:应用二甲基亚硝胺(DMN)建立肝纤维化大鼠模型,动态观察疏肝健脾活血方对肝纤维化大鼠肝组织中HIF-1α蛋白、VEGF m RNA表达的影响,探讨疏肝健脾活血方抗肝纤维化的作用机制。方法:90只大鼠随机分为正常2、4、6周组,模型2、4、6周组...目的:应用二甲基亚硝胺(DMN)建立肝纤维化大鼠模型,动态观察疏肝健脾活血方对肝纤维化大鼠肝组织中HIF-1α蛋白、VEGF m RNA表达的影响,探讨疏肝健脾活血方抗肝纤维化的作用机制。方法:90只大鼠随机分为正常2、4、6周组,模型2、4、6周组,中药2、4、6周组,共9组,每组10只。采用DMN腹腔注射建立肝纤维化大鼠模型,同时中药各组给予疏肝健脾活血方灌胃。观察各组大鼠肝纤维化病理形态学改变,Westernblot法检测肝组织HIF-1α蛋白,RT-PCR法检测肝组织VEGF m RNA表达情况。结果:与正常各组同期比较,模型各组及中药各组大鼠肝组织HIF-1α蛋白、VEGF m RNA表达量均增高(P<0.01,P<0.05);与模型各组同期比较,中药4、6周组肝组织HIF-1α蛋白、VEGF m RNA表达量均降低(P<0.05,P<0.01)。结论:疏肝健脾活血方可减轻肝脏纤维化程度;降低肝组织HIF-1α蛋白、VEGF m RNA表达量,可能是其抗肝纤维化作用机制之一。展开更多
Shape-selective methylation of 2-methylnaphthalene (2-MN) was carried out over NH 4 F and Pt modified HZSM-5 (SiO 2 /Al 2 O 3 = 83) catalysts in a fixed-bed down-flow reactor using methanol as methylating agent and 1,...Shape-selective methylation of 2-methylnaphthalene (2-MN) was carried out over NH 4 F and Pt modified HZSM-5 (SiO 2 /Al 2 O 3 = 83) catalysts in a fixed-bed down-flow reactor using methanol as methylating agent and 1,3,5-trimethylbenzene (1,3,5-TMB) as a solvent. Pt promoted HZSM-5 catalysts showed low concentration of coke-like polycondensed aromatics, NH 4 F modification decreased non-shape-selective acid sites. After Pt and NH 4 F co-modification, both conversion of 2-MN and selectivity to 2,6-DMN were improved. 6%NH 4 F/0.5%Pt/HZSM-5 catalyst exhibited 13.8% of 2-MN conversion with 6.2% of 2,6-DMN yield after 7 h time on stream (TOS), and 2,6-/2,7-DMN ratio of 1.7 after 10 h of TOS.展开更多
文摘AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with lie and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 Iobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P〈0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.
基金Supported by National Natural Science Foundation of China,No.81072913
文摘AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine(DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin(IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells(KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were cocultured with KCs in vitro to assess the effects of UCMSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UCMSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the coculture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.
文摘目的研究杠板归总黄酮对二甲基亚硝胺(DMN)诱导的肝纤维化大鼠的拮抗作用。方法将120只SD大鼠随机均分成正常组、模型组、秋水仙碱组和杠板归总黄酮高、中、低剂量(0.15、0.1、0.5 g·kg-1)组。除正常组外,各组大鼠均ip0.5%DMN溶液2.0 m L·kg-1,隔天注射1次,造模成功后,各给药组均ig给药,qd,连续8周,正常组与模型组ig等量生理盐水。于8周末取血和肝脏,酶联免疫吸附法检测血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)和转化生长因子β1(TGF-β1);HE染色观察肝纤维化(HF)形成;Western blot法检测肝组织中TGF-β1的表达。结果与模型组比较,杠板归总黄酮各剂量均可有效降低HF大鼠血清中HA、LN、PCⅢ和TGF-B1的水平;杠板归总黄酮可明显降低HF大鼠肝脏中TGF-β1的表达。结论杠板归总黄酮对DMN诱导的大鼠HF具有良好的拮抗作用,可能通过抗肝损伤和降低TGF-β1的表达来实现。
文摘目的:应用二甲基亚硝胺(DMN)建立肝纤维化大鼠模型,动态观察疏肝健脾活血方对肝纤维化大鼠肝组织中HIF-1α蛋白、VEGF m RNA表达的影响,探讨疏肝健脾活血方抗肝纤维化的作用机制。方法:90只大鼠随机分为正常2、4、6周组,模型2、4、6周组,中药2、4、6周组,共9组,每组10只。采用DMN腹腔注射建立肝纤维化大鼠模型,同时中药各组给予疏肝健脾活血方灌胃。观察各组大鼠肝纤维化病理形态学改变,Westernblot法检测肝组织HIF-1α蛋白,RT-PCR法检测肝组织VEGF m RNA表达情况。结果:与正常各组同期比较,模型各组及中药各组大鼠肝组织HIF-1α蛋白、VEGF m RNA表达量均增高(P<0.01,P<0.05);与模型各组同期比较,中药4、6周组肝组织HIF-1α蛋白、VEGF m RNA表达量均降低(P<0.05,P<0.01)。结论:疏肝健脾活血方可减轻肝脏纤维化程度;降低肝组织HIF-1α蛋白、VEGF m RNA表达量,可能是其抗肝纤维化作用机制之一。
基金Supported by the Program for New Century Excellent Talents in University (NCET-04-0268)the Expertise-Introduction Project for Disciplinary Innovation of Universities
文摘Shape-selective methylation of 2-methylnaphthalene (2-MN) was carried out over NH 4 F and Pt modified HZSM-5 (SiO 2 /Al 2 O 3 = 83) catalysts in a fixed-bed down-flow reactor using methanol as methylating agent and 1,3,5-trimethylbenzene (1,3,5-TMB) as a solvent. Pt promoted HZSM-5 catalysts showed low concentration of coke-like polycondensed aromatics, NH 4 F modification decreased non-shape-selective acid sites. After Pt and NH 4 F co-modification, both conversion of 2-MN and selectivity to 2,6-DMN were improved. 6%NH 4 F/0.5%Pt/HZSM-5 catalyst exhibited 13.8% of 2-MN conversion with 6.2% of 2,6-DMN yield after 7 h time on stream (TOS), and 2,6-/2,7-DMN ratio of 1.7 after 10 h of TOS.