目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个...目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。展开更多
α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironme...α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.展开更多
Objective： The aim of this case-control study was to explore whether five tagging single nucleotide poly- morphisms （tSNPs） within the transforming growth factor-ill （TGF-fll） gene were involved in manifestation ...Objective： The aim of this case-control study was to explore whether five tagging single nucleotide poly- morphisms （tSNPs） within the transforming growth factor-ill （TGF-fll） gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers pneumoconiosis （CWP）. Methods： The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Results： The single SNP analysis showed that the genotype frequencies of SNP2 （rs1800470, ＋869T/C, extron 1） and SNP5 （rs11466345, intron 5） in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 （rs1800470） CC genotype was associated with decreased risk of CWP （OR = 0.50, 95% CI = 0.32-0.78）, which was evident among subgroups of those never smoke （OR = 0.40, 95%CI = 0.24-0.66）, cases with stage Ⅱ（OR = 0.41, 95%CI = 0.22-0.76） and exposure period （〈 28 y： OR = 0.54, 95%CI = 0.31-0.95; ≥ 28 y： OR = 0.52, 95%CI = 0.32-0.96）. However, the SNP5 （rs11466345） GG genotype was associated with an increased risk of CWP （OR = 2.5, 95%CI = 1.36-4.57）, and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and Ⅱ. Conclusion： This study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.展开更多
文摘目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。
基金funded by National Nature Science Foundation of China (Grant Nos 30970705, 11172190, 81371171, and 81371172)
文摘α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.
基金supported by the National Natural Science Foundation of China(No.30872093)Research Foundation of Health Department of Jiangsu Province(No.H200628)
文摘Objective： The aim of this case-control study was to explore whether five tagging single nucleotide poly- morphisms （tSNPs） within the transforming growth factor-ill （TGF-fll） gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers pneumoconiosis （CWP）. Methods： The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Results： The single SNP analysis showed that the genotype frequencies of SNP2 （rs1800470, ＋869T/C, extron 1） and SNP5 （rs11466345, intron 5） in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 （rs1800470） CC genotype was associated with decreased risk of CWP （OR = 0.50, 95% CI = 0.32-0.78）, which was evident among subgroups of those never smoke （OR = 0.40, 95%CI = 0.24-0.66）, cases with stage Ⅱ（OR = 0.41, 95%CI = 0.22-0.76） and exposure period （〈 28 y： OR = 0.54, 95%CI = 0.31-0.95; ≥ 28 y： OR = 0.52, 95%CI = 0.32-0.96）. However, the SNP5 （rs11466345） GG genotype was associated with an increased risk of CWP （OR = 2.5, 95%CI = 1.36-4.57）, and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and Ⅱ. Conclusion： This study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.
