Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are invo...Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.展开更多
目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组...目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组大鼠夹闭股动脉缺血3h,再灌注3h;Sevo预处理+IR组(SIR组)吸入2.5%七氟烷30min,15min后制备肢体IR模型。实验结束后留取左肺,测定肺组织湿干/重比(W/D)和总肺水含量(TLW),光镜下观察肺组织病理学改变并测定肺组织损伤定量评估(IQA),电镜下观察肺组织超微结构改变,反转录-PCR(RT-PCR)和蛋白免疫印迹法(Western blot法)分别检测肺组织葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)的表达水平。结果与Sham组比较,IR组大鼠肺组织W/D、TLW和IQA均升高(P<0.05)。SIR组大鼠肺组织W/D、TLW和IQA均较IR组降低(P<0.05)。IR组大鼠肺组织形态学结构和超微结构发生明显损伤,而SIR组大鼠肺组织形态学结构和超微结构损伤均明显减轻。与Sham组比较,IR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均升高(P<0.05)。而SIR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均较IR组降低(P<0.05)。结论七氟烷预处理对肢体IR所致肺损伤发生的大鼠肺脏具有较好的保护作用,其机制可能与其抑制肺组织中过度的未折叠蛋白反应(UPR)有关。展开更多
基金This work was supported by grants from Zhejiang Provincial Natural Science Foundation of China （No.Y12H070014） and National Natural Science Foundation of China （No.30972592）.
文摘Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.
文摘目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组大鼠夹闭股动脉缺血3h,再灌注3h;Sevo预处理+IR组(SIR组)吸入2.5%七氟烷30min,15min后制备肢体IR模型。实验结束后留取左肺,测定肺组织湿干/重比(W/D)和总肺水含量(TLW),光镜下观察肺组织病理学改变并测定肺组织损伤定量评估(IQA),电镜下观察肺组织超微结构改变,反转录-PCR(RT-PCR)和蛋白免疫印迹法(Western blot法)分别检测肺组织葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)的表达水平。结果与Sham组比较,IR组大鼠肺组织W/D、TLW和IQA均升高(P<0.05)。SIR组大鼠肺组织W/D、TLW和IQA均较IR组降低(P<0.05)。IR组大鼠肺组织形态学结构和超微结构发生明显损伤,而SIR组大鼠肺组织形态学结构和超微结构损伤均明显减轻。与Sham组比较,IR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均升高(P<0.05)。而SIR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均较IR组降低(P<0.05)。结论七氟烷预处理对肢体IR所致肺损伤发生的大鼠肺脏具有较好的保护作用,其机制可能与其抑制肺组织中过度的未折叠蛋白反应(UPR)有关。
