目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性S...目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后支架内再狭窄(in-stent restenosis,ISR)的关系。方法纳入128例接受急诊PCI的STEMI患者,随访12个月后根据冠状动脉造影结果分为非ISR组(80例)和ISR组(48例)。比较两组的一般资料,出院前及术后1个月EFT,术前及术后1个月血清SFRP5、Wnt5a水平,以及不同冠状动脉病变程度患者指标水平的差异。采用Pearson相关性分析,评估术后1个月EFT和血清SFRP5、Wnt5a水平的相关性。采用多因素Logistic回归分析,确定STEMI患者PCI术后发生ISR的危险因素。采用ROC曲线分析,评估EFT和血清SFRP5、Wnt5a水平对ISR的预测价值。结果ISR组出院前及术后1个月EFT均大于非ISR组;术后1个月血清SFRP5低于非ISR组,血清Wnt5a高于非ISR组(均P<0.01)。非ISR组术后1个月血清SFRP5较术前显著升高,而ISR组则显著降低;非ISR组术后1个月血清Wnt5a较术前轻度升高,ISR组则显著升高(均P<0.05)。3支病变组术后1个月血清SFRP5显著低于单支或2支病变组(P<0.05)。术后1个月EFT与SFRP5呈负相关,与Wnt5a呈正相关。单因素Logistic回归分析及校正年龄、BMI等因素后的Logistic回归分析均显示,术后1个月EFT、血清SFRP5和Wnt5a是ISR的独立影响因素。ROC曲线分析显示,三者联合检测的AUC值(0.906)高于单一指标检测。结论STEMI患者术后1个月EFT增大、血清SFRP5降低及Wnt5a升高与PCI术后ISR密切相关,早期检查有助于预测ISR,联合检测的预测价值更高。展开更多
目的观察腓肠肌钝挫伤白兔的腓肠肌中的无翅型MMTV整合位点家族成员5a(wingless-type MMTV integration site family member 5a,Wnt5a)、糖原合成酶激酶3(glycogen synthase kinase 3,GSK3)/β-联蛋白(β-catenin)的mRNA和蛋白表达,以...目的观察腓肠肌钝挫伤白兔的腓肠肌中的无翅型MMTV整合位点家族成员5a(wingless-type MMTV integration site family member 5a,Wnt5a)、糖原合成酶激酶3(glycogen synthase kinase 3,GSK3)/β-联蛋白(β-catenin)的mRNA和蛋白表达,以及病理染色中呈现的肌肉纤维、脂肪组织的情况,为揭示按揉法治疗骨骼肌损伤的修复机制提供依据。方法选择健康新西兰白兔42只,雌雄各半。采用随机数字表法将其分为空白组、模型3 d组、模型7 d组、模型14 d组、按揉3 d组、按揉7 d组、按揉14 d组,每组6只。各模型组、按揉组在操作后第4、8、15天取材。采用实时定量聚合酶链反应和蛋白质印迹法检测Wnt5a、GSK3、β-catenin的mRNA和蛋白表达情况;采用苏木精-伊红(hematoxylin and eosin,HE)染色和油红O染色观察肌肉组织肌纤维及脂肪组织的情况。结果HE染色显示,模型7 d组发生显著纤维组织增生和炎性细胞浸润;模型14 d组可见部分肌纤维变性坏死、再生伴纤维组织增生及轻微炎性细胞浸润,轻微钙化;各按揉组可见明显肌纤维变性坏死、再生,炎性细胞浸润伴随显著纤维组织增生。油红O染色显示,各模型组可见脂肪细胞沉积,其中模型7 d组最重;各按揉组肌肉纤维及序列未见明显破坏,间隙可见少量脂肪细胞浸润。各组腓肠肌Wnt5a、GSK3、β-catenin的mRNA表达与蛋白表达比较,差异均有统计学意义(P<0.001)。结论腓肠肌损伤组织病理变化随着时间推移会逐渐恢复,按揉法刺激了Wnt5a、GSK3、β-catenin的mRNA的表达活性,从而可能减缓支架蛋白复合物(GSK3为其重要的组成部分)对β-catenin蛋白的降解,使β-catenin的蛋白水平始终维持在稳定范围,使得按揉法干预后的腓肠肌中脂肪变性减少,促进了损伤骨骼肌功能修复。展开更多
目的探讨补骨脂素通过调控无翅型MMTV整合位点家族(wingless type MMTV integration site family,Wnt)信号通路对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠的骨保护作用机制。方法将60只SPF级SD雌性大鼠随机分为空白组...目的探讨补骨脂素通过调控无翅型MMTV整合位点家族(wingless type MMTV integration site family,Wnt)信号通路对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠的骨保护作用机制。方法将60只SPF级SD雌性大鼠随机分为空白组、模型组、雌二醇片组(0.09mg/kg,每日1次)和补骨脂素低、中、高剂量组(分别为11、22、44mg/kg,每日3次),每组10只。除空白组外,其余组以去卵巢方法构建PMOP大鼠模型。药物干预6周后麻醉取材,行股骨骨密度测定;苏木精-伊红(hematoxylin-eosin,HE)染色观察股骨组织病理形态;逆转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)检测大鼠股骨组织Dickkopf相关蛋白1(dickkopf-related protein 1,DKK1)、β-连环蛋白(β-catenin)、Runt相关转录因子2(runt-related transcription factor 2,Runx2)mRNA表达。结果①股骨骨密度方面,与空白组比较,模型组大鼠的双侧股骨骨密度明显降低(P均<0.05);与模型组比较,雌二醇片组、补骨脂素高剂量组大鼠的双侧股骨骨密度及补骨脂素低、中剂量组大鼠的左侧股骨骨密度均明显升高(P均<0.05);与雌二醇片组比较,补骨脂素低剂量组大鼠的双侧股骨骨密度较低(P<0.05)。②股骨组织病理形态方面,与空白组比较,模型组大鼠的股骨骨小梁结构破坏明显且排列紊乱,骨吸收孔增多,骨质疏松特征明显;与模型组比较,雌二醇片组和补骨脂素低、中、高剂量组大鼠的股骨骨小梁结构有所改善,其中,雌二醇片组与补骨脂素高剂量组的骨小梁连续性明显增加,骨陷窝缩小,骨吸收孔减少。③mRNA表达方面,与空白组比较,模型组大鼠股骨组织的DKK1mRNA表达水平明显升高,而β-catenin、Runx2mRNA表达水平明显降低(P均<0.05);与模型组比较,雌二醇片组以及补骨脂素中、高剂量组大鼠股骨组织的DKK1mRNA表达水平明显降低(P<0.05),而β-catenin、Runx2mRNA表达水平明显升高(P均<0.05);与雌二醇片组比较,补骨脂素低剂量组β-catenin、Runx2mRNA表达水平降低(P均<0.05),补骨脂素中、高剂量组大鼠股骨组织的DKK1、β-catenin、Runx2mRNA表达水平差异无统计学意义(P均>0.05)。结论补骨脂素可能通过抑制DKK1表达,进而激活Wnt/β-catenin信号通路,上调Runx2水平,增强骨形成,最终对PMOP大鼠发挥骨保护作用。展开更多
The wingless-related integration site(WNT)proteins are a family of secreted glycoproteins that are evolutionarily conserved and are believed to be involved in evolution in vertebrates and invertebrates.WNT signaling p...The wingless-related integration site(WNT)proteins are a family of secreted glycoproteins that are evolutionarily conserved and are believed to be involved in evolution in vertebrates and invertebrates.WNT signaling pathways may be associated with limb regeneration and development in crustaceans.However,the detail mechanisms remain unclear.Therefore,the distribution of WNT4 in the hepatopancreas,muscle,hemocyte,ganglion,heart,eyestalk,gill tissue,and diff erent larvae development stages of the swimming crab(Portunus trituberculatus)were characterized using immunofl uorescence,real-time PCR,and Western blotting.Signifi cant PtWNT4 expression was detected in heart and eyestalk.In addition,PtWNT4 was expressed in all larval stages of P.trituberculatus with a dynamic expression pattern,especially in the eyestalk and other organs in the carapace area.The injection of WNT4 dsRNA into regenerative limbs signifi cantly decreased PtWNT4 mRNA levels in the eyestalk,heart,and muscle,resulting in 1.9-fold,2.2-fold,and 2.7-fold decreases compared with those detected in the group injected with crab saline(P<0.05),respectively,indicating successful gene silencing.Overall,expression analysis on the WNT4 using RNAi provides an insight to its functional mechanism during limb regeneration in P.trituberculatus.The results not only demonstrated the requirement for WNT4 in limb regeneration of Crustaceans,but also suggested its ability to promote larval development at specifi c stages.展开更多
文摘目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后支架内再狭窄(in-stent restenosis,ISR)的关系。方法纳入128例接受急诊PCI的STEMI患者,随访12个月后根据冠状动脉造影结果分为非ISR组(80例)和ISR组(48例)。比较两组的一般资料,出院前及术后1个月EFT,术前及术后1个月血清SFRP5、Wnt5a水平,以及不同冠状动脉病变程度患者指标水平的差异。采用Pearson相关性分析,评估术后1个月EFT和血清SFRP5、Wnt5a水平的相关性。采用多因素Logistic回归分析,确定STEMI患者PCI术后发生ISR的危险因素。采用ROC曲线分析,评估EFT和血清SFRP5、Wnt5a水平对ISR的预测价值。结果ISR组出院前及术后1个月EFT均大于非ISR组;术后1个月血清SFRP5低于非ISR组,血清Wnt5a高于非ISR组(均P<0.01)。非ISR组术后1个月血清SFRP5较术前显著升高,而ISR组则显著降低;非ISR组术后1个月血清Wnt5a较术前轻度升高,ISR组则显著升高(均P<0.05)。3支病变组术后1个月血清SFRP5显著低于单支或2支病变组(P<0.05)。术后1个月EFT与SFRP5呈负相关,与Wnt5a呈正相关。单因素Logistic回归分析及校正年龄、BMI等因素后的Logistic回归分析均显示,术后1个月EFT、血清SFRP5和Wnt5a是ISR的独立影响因素。ROC曲线分析显示,三者联合检测的AUC值(0.906)高于单一指标检测。结论STEMI患者术后1个月EFT增大、血清SFRP5降低及Wnt5a升高与PCI术后ISR密切相关,早期检查有助于预测ISR,联合检测的预测价值更高。
基金Supported by the National Natural Science Foundation of China(No.31602152)the Major Agriculture Program of Ningbo(No.2017C110007)the K.C.Wong Magana Fund in Ningbo University.The funding body had no role in the study design,experimental implementation,interpretation of data,or writing of the manuscript。
文摘The wingless-related integration site(WNT)proteins are a family of secreted glycoproteins that are evolutionarily conserved and are believed to be involved in evolution in vertebrates and invertebrates.WNT signaling pathways may be associated with limb regeneration and development in crustaceans.However,the detail mechanisms remain unclear.Therefore,the distribution of WNT4 in the hepatopancreas,muscle,hemocyte,ganglion,heart,eyestalk,gill tissue,and diff erent larvae development stages of the swimming crab(Portunus trituberculatus)were characterized using immunofl uorescence,real-time PCR,and Western blotting.Signifi cant PtWNT4 expression was detected in heart and eyestalk.In addition,PtWNT4 was expressed in all larval stages of P.trituberculatus with a dynamic expression pattern,especially in the eyestalk and other organs in the carapace area.The injection of WNT4 dsRNA into regenerative limbs signifi cantly decreased PtWNT4 mRNA levels in the eyestalk,heart,and muscle,resulting in 1.9-fold,2.2-fold,and 2.7-fold decreases compared with those detected in the group injected with crab saline(P<0.05),respectively,indicating successful gene silencing.Overall,expression analysis on the WNT4 using RNAi provides an insight to its functional mechanism during limb regeneration in P.trituberculatus.The results not only demonstrated the requirement for WNT4 in limb regeneration of Crustaceans,but also suggested its ability to promote larval development at specifi c stages.
