Objective To investigate the cardioprotective effect of Danqi Tablet(DQT,丹七片)on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γcoactiva...Objective To investigate the cardioprotective effect of Danqi Tablet(DQT,丹七片)on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α).Methods Rat ischemic heart model was induced by ligation of left anterior descending coronary artery.Totally 40 Sprague-Dawley rats were randomly divided into sham group,model group,DQT group(1.5 mg/kg daily)and trimetazidine(TMZ)group(6.3 mg/kg daily)according to a random number table,10 rats in each group.Twenty-eight days after continuous administration,cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining.The level of adenosine triphosphate(ATP)in myocardial cells was measured by ATP assay kit.Expressions level of key transcriptional regulators,including PGC-1α,Sirtuin 1(SIRT1),AMP-activated protein kinase(AMPK),and downstream targets of PGC-1α,such as mitofusin 1(MFN1),mitofusin 2(MFN2)and superoxide dismutase 2(SOD2)were measured by Western blot.Expression level of PGC-1αwas examined by immunohistochemical staining.Results The rat ischemic heart model was successfully induced and the heart function in model group was compromised.Compared with the model group,DQT exerted cardioprotective effects,up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues(P<0.01).The expressions of PGC-1α,SIRT1 and AMPK were increased in the DQT group(all P<0.05).Furthermore,the downstream targets,including MFN1,MFN2 and SOD2 were up-regulated(P<0.05 or P<0.01).Compared with the TMZ group,the expression levels of PGC-1α,MFN1 and SOD2 were increased by DQT treatment(P<0.05 or P<0.01).Conclusion DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1-PGC-1αpathway.PGC-1αmight serve as a promising target in the treatment of ischemic heart disease.展开更多
罗非鱼全雄养殖可有效控制繁殖、提高养殖效率,遗传全雄罗非鱼(Genetically male tilapia,GMT)技术是性别控制的高效手段,但GMT技术培育的鱼苗雄性率不稳定。基因组学和基因编辑等技术已广泛应用于罗非鱼研究,极大地促进了罗非鱼性别决...罗非鱼全雄养殖可有效控制繁殖、提高养殖效率,遗传全雄罗非鱼(Genetically male tilapia,GMT)技术是性别控制的高效手段,但GMT技术培育的鱼苗雄性率不稳定。基因组学和基因编辑等技术已广泛应用于罗非鱼研究,极大地促进了罗非鱼性别决定与分化基础理论研究。分析导致XY个体性别逆转的可能因素,提出将来GMT技术研究的关键问题,探讨现代基因编辑技术在罗非鱼性别控制育种中可能应用。展开更多
有机锡的外暴露能引起脊椎动物胚胎的独特畸形,但通过母体传递引起的内暴露毒性还缺乏研究.本文通过显微注射的方式研究了三苯基锡(TPT)、过氧化物酶体增殖体激活受体γ(PPARγ)的激动剂罗格列酮(Rosi)和抑制剂T0070907(C_(12)H_8ClN_3O...有机锡的外暴露能引起脊椎动物胚胎的独特畸形,但通过母体传递引起的内暴露毒性还缺乏研究.本文通过显微注射的方式研究了三苯基锡(TPT)、过氧化物酶体增殖体激活受体γ(PPARγ)的激动剂罗格列酮(Rosi)和抑制剂T0070907(C_(12)H_8ClN_3O_3)对热带爪蟾胚胎的发育毒性.将3种化合物注入S1一S2期的胚胎后,胚胎的存活率显著下降,其中5 ng TPT,80 ng Rosi和10 ng T0070907注射组存活率分别为46.9%、42.7%和54.2%.胚胎的体长也受到不同程度的影响,5 ng TPT,80 ng Rosi和20 ng T0070907注射组与对照相比体长分别减少了27%、22%和57%.3种化合物还引起了多样的畸形效应,尤其是头部变小及眼睛畸形.说明PPARγ在热带爪蟾早期胚胎的发育特别是头、眼发育中扮演非常重要的角色.TPT与相近剂量T0070907引起的畸形非常相似,说明TPT的致畸机制可能与PPARγ存在某种关系.另一方面,利用整胚原位杂交检测了注射TPT后S20及S25期胚胎的头、眼部标志基因的空间表达,结果表明bf1、en2、krox20及pax6的表达信号均随TPT剂量增大而逐渐变弱且区域变小,定量PCR进一步验证了TPT能在神经胚及早期尾牙期之前影响胚胎头、眼标志基因的表达.研究结果表明,TPT的内暴露对脊椎动物胚胎具有较强的致畸效应和神经毒性.展开更多
基金Supported by the National Natural Science Foundation of China(No.81503379,81822049,and 81673712)。
文摘Objective To investigate the cardioprotective effect of Danqi Tablet(DQT,丹七片)on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α).Methods Rat ischemic heart model was induced by ligation of left anterior descending coronary artery.Totally 40 Sprague-Dawley rats were randomly divided into sham group,model group,DQT group(1.5 mg/kg daily)and trimetazidine(TMZ)group(6.3 mg/kg daily)according to a random number table,10 rats in each group.Twenty-eight days after continuous administration,cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining.The level of adenosine triphosphate(ATP)in myocardial cells was measured by ATP assay kit.Expressions level of key transcriptional regulators,including PGC-1α,Sirtuin 1(SIRT1),AMP-activated protein kinase(AMPK),and downstream targets of PGC-1α,such as mitofusin 1(MFN1),mitofusin 2(MFN2)and superoxide dismutase 2(SOD2)were measured by Western blot.Expression level of PGC-1αwas examined by immunohistochemical staining.Results The rat ischemic heart model was successfully induced and the heart function in model group was compromised.Compared with the model group,DQT exerted cardioprotective effects,up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues(P<0.01).The expressions of PGC-1α,SIRT1 and AMPK were increased in the DQT group(all P<0.05).Furthermore,the downstream targets,including MFN1,MFN2 and SOD2 were up-regulated(P<0.05 or P<0.01).Compared with the TMZ group,the expression levels of PGC-1α,MFN1 and SOD2 were increased by DQT treatment(P<0.05 or P<0.01).Conclusion DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1-PGC-1αpathway.PGC-1αmight serve as a promising target in the treatment of ischemic heart disease.
文摘罗非鱼全雄养殖可有效控制繁殖、提高养殖效率,遗传全雄罗非鱼(Genetically male tilapia,GMT)技术是性别控制的高效手段,但GMT技术培育的鱼苗雄性率不稳定。基因组学和基因编辑等技术已广泛应用于罗非鱼研究,极大地促进了罗非鱼性别决定与分化基础理论研究。分析导致XY个体性别逆转的可能因素,提出将来GMT技术研究的关键问题,探讨现代基因编辑技术在罗非鱼性别控制育种中可能应用。
文摘有机锡的外暴露能引起脊椎动物胚胎的独特畸形,但通过母体传递引起的内暴露毒性还缺乏研究.本文通过显微注射的方式研究了三苯基锡(TPT)、过氧化物酶体增殖体激活受体γ(PPARγ)的激动剂罗格列酮(Rosi)和抑制剂T0070907(C_(12)H_8ClN_3O_3)对热带爪蟾胚胎的发育毒性.将3种化合物注入S1一S2期的胚胎后,胚胎的存活率显著下降,其中5 ng TPT,80 ng Rosi和10 ng T0070907注射组存活率分别为46.9%、42.7%和54.2%.胚胎的体长也受到不同程度的影响,5 ng TPT,80 ng Rosi和20 ng T0070907注射组与对照相比体长分别减少了27%、22%和57%.3种化合物还引起了多样的畸形效应,尤其是头部变小及眼睛畸形.说明PPARγ在热带爪蟾早期胚胎的发育特别是头、眼发育中扮演非常重要的角色.TPT与相近剂量T0070907引起的畸形非常相似,说明TPT的致畸机制可能与PPARγ存在某种关系.另一方面,利用整胚原位杂交检测了注射TPT后S20及S25期胚胎的头、眼部标志基因的空间表达,结果表明bf1、en2、krox20及pax6的表达信号均随TPT剂量增大而逐渐变弱且区域变小,定量PCR进一步验证了TPT能在神经胚及早期尾牙期之前影响胚胎头、眼标志基因的表达.研究结果表明,TPT的内暴露对脊椎动物胚胎具有较强的致畸效应和神经毒性.
