Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detec...Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases,since many clinically relevant decisions,such as starting treatment and/or monitoring for complications including hepatocellular carcinoma,may depend on it.The gold standard for fibrosis staging is liver biopsy,the role of which,however,is questioned nowadays because of cost,hazards and poor acceptance by patients.On the other hand,imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy.Making progress in this field is nowmore crucial than ever,since treatments for established fibrosis appear on the horizon.Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis,such as growth arrest-specific6,Mac-2-binding protein,osteopontin,placental growth factor,growth/differentiation factor 15 and hepatocyte growth factor.All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases.Here,we review the pros and cons for their use in this setting.展开更多
目的:观察积雪草颗粒对TGF-β1诱导的体外培养的肾小管上皮细胞单核细胞趋化蛋白1(MCP-1)、肝细胞生长因子(HGF)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)m RNA表达的影响。方法:将体外培养的大鼠近端肾小管上皮细胞(...目的:观察积雪草颗粒对TGF-β1诱导的体外培养的肾小管上皮细胞单核细胞趋化蛋白1(MCP-1)、肝细胞生长因子(HGF)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)m RNA表达的影响。方法:将体外培养的大鼠近端肾小管上皮细胞(NRK52E)随机分为6组:正常对照组、TGF-β1刺激组、积雪草小、中、大剂量组及蒙诺组。培养48h后取出,应用实时荧光定量PCR技术检测细胞MCP-1、HGF、MMP-2、TIMP-2的m RNA表达。结果:与正常对照组比较,TGF-β1刺激组细胞MCP-1、MMP-2、TIMP-2的m RNA表达明显升高(P<0.05),HGF m RNA表达显著增加(P<0.05);各药物干预组与TGF-β1刺激组相比MCP-1、MMP-2、TIMP-2的m RNA明显下降(P<0.05),HGF m RNA表达明显增加(P<0.05);蒙诺组细胞变化与积雪草大剂量组相似。结论:积雪草抗TIF作用可能通过抑制MCP-1、MMP-2、TIMP-2的高表达,上调HGF的表达,调节MMP-2/TIMP-2的平衡而实现,且与其剂量呈正相关。展开更多
Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of...Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction （UUO）. We divided 48 Sprague-Dawley rats randomly into 4 groups： sham-operated group （Sham）, untreated UUO group, AM-treated （10 g/（kg.d）） UUO group, and losartan-treated （20 mg/（kg.d）） UUO group as positive control. Haematoxylin ＆ eosin （HE） and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin （FN）, type I collagen （coil）, hepatocyte growth factor （HGF）, transforming growth factor-β1 （TGF-β1）, and eL-smooth muscle actin （α-SMA） were analyzed by real-time polymerase chain reaction （PCR）, immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 and α-SMA （P〈0.05）, whereas HGF increased greatly with AM treatment （P〈0.05）. Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.展开更多
文摘Repair of sustained liver injury results in fibrosis(i.e.the accumulation of extracellular matrix proteins),and ultimately the complete distortion of parenchymal architecture of the liver,which we call cirrhosis.Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases,since many clinically relevant decisions,such as starting treatment and/or monitoring for complications including hepatocellular carcinoma,may depend on it.The gold standard for fibrosis staging is liver biopsy,the role of which,however,is questioned nowadays because of cost,hazards and poor acceptance by patients.On the other hand,imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy.Making progress in this field is nowmore crucial than ever,since treatments for established fibrosis appear on the horizon.Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis,such as growth arrest-specific6,Mac-2-binding protein,osteopontin,placental growth factor,growth/differentiation factor 15 and hepatocyte growth factor.All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases.Here,we review the pros and cons for their use in this setting.
文摘目的:观察积雪草颗粒对TGF-β1诱导的体外培养的肾小管上皮细胞单核细胞趋化蛋白1(MCP-1)、肝细胞生长因子(HGF)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)m RNA表达的影响。方法:将体外培养的大鼠近端肾小管上皮细胞(NRK52E)随机分为6组:正常对照组、TGF-β1刺激组、积雪草小、中、大剂量组及蒙诺组。培养48h后取出,应用实时荧光定量PCR技术检测细胞MCP-1、HGF、MMP-2、TIMP-2的m RNA表达。结果:与正常对照组比较,TGF-β1刺激组细胞MCP-1、MMP-2、TIMP-2的m RNA表达明显升高(P<0.05),HGF m RNA表达显著增加(P<0.05);各药物干预组与TGF-β1刺激组相比MCP-1、MMP-2、TIMP-2的m RNA明显下降(P<0.05),HGF m RNA表达明显增加(P<0.05);蒙诺组细胞变化与积雪草大剂量组相似。结论:积雪草抗TIF作用可能通过抑制MCP-1、MMP-2、TIMP-2的高表达,上调HGF的表达,调节MMP-2/TIMP-2的平衡而实现,且与其剂量呈正相关。
基金(No.30170437) supported by the National Natural Science Foundation of China
文摘Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction （UUO）. We divided 48 Sprague-Dawley rats randomly into 4 groups： sham-operated group （Sham）, untreated UUO group, AM-treated （10 g/（kg.d）） UUO group, and losartan-treated （20 mg/（kg.d）） UUO group as positive control. Haematoxylin ＆ eosin （HE） and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin （FN）, type I collagen （coil）, hepatocyte growth factor （HGF）, transforming growth factor-β1 （TGF-β1）, and eL-smooth muscle actin （α-SMA） were analyzed by real-time polymerase chain reaction （PCR）, immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 and α-SMA （P〈0.05）, whereas HGF increased greatly with AM treatment （P〈0.05）. Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.
