OBJECTIVE Here we investigated the effects and the underlying mechanism of Ginkgolide K(1,10-dihydroxy-3,14-didehydroginkgolide,GK)on cardiac ER stress.METHODS Cell death,apoptosis,and ER stressrelated signalling path...OBJECTIVE Here we investigated the effects and the underlying mechanism of Ginkgolide K(1,10-dihydroxy-3,14-didehydroginkgolide,GK)on cardiac ER stress.METHODS Cell death,apoptosis,and ER stressrelated signalling pathwayswere measuredin cultured neonatal rat cardiomyocytes(NRCMs),treated with the ER stress inducers tunicamycin,hydrogen peroxide,and thapsigargin.Acute myocardial infarction was established using left coronary artery occlusion in mice,and infarct size was measured by triphenyltetrazolium chloride(TTC)staining.Echocardiography was used to assess heart function and transmission electron microscopy for evaluating ER expansion.RESULTS GK significantly decreased ER stress-induced cell death in both in vitro and in vivomodels.In ischemic injured mice,GK treatment reduced infarct size,rescued heart dysfunction and ameliorated ER dilation.Mechanistic studies revealed that the beneficial effects of GK occur through enhancement of inositol-requiring enzyme 1α(IRE1α)/X box-binding protein-1(XBP1)activity,which in turn leads to increased ER-associated degradation(ERAD)-mediated clearance of misfolded proteins and autophagy.In addition,GK is also able to partially repress the pro-apoptotic action of regulated IRE1-dependent decay(RIDD)and JNK pathway.CONCLUSION GK acts through selective activation of the IRE1α/XBP1 pathway to limit ER stress injury.GK is revealed as a promising therapeutic agent to ameliorate ER stress for treating cardiovascular diseases.展开更多
目的观察糖脂平方治疗非增殖期糖尿病视网膜病变(NPDR)的临床疗效及对血清血管内皮细胞生长因子(VEGF)和色素上皮衍生因子(PEDF)的影响。方法将86例NPDR患者随机分为治疗组和对照组各43例。2组均予降糖、降压、调脂基础治疗。对照组予...目的观察糖脂平方治疗非增殖期糖尿病视网膜病变(NPDR)的临床疗效及对血清血管内皮细胞生长因子(VEGF)和色素上皮衍生因子(PEDF)的影响。方法将86例NPDR患者随机分为治疗组和对照组各43例。2组均予降糖、降压、调脂基础治疗。对照组予羟苯磺酸钙胶囊,每次0.5 g,每日3次,口服;治疗组在对照组基础上予糖脂平方,每次1剂,每日2次,口服。均4周为1个疗程,连续治疗3个疗程。评价2组临床疗效及眼底疗效,观察中医症状积分、眼底积分、视力情况,检测空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及血清VEGF、PEDF含量变化。结果对照组与治疗组分别脱落2、3例。对照组临床疗效、眼底疗效总有效率分别为65.00%、68.35%,治疗组分别为87.50%、84.62%,2组比较差异有统计学意义(P<0.05)。与本组治疗前比较,2组治疗后中医症状积分、眼底积分明显下降(P<0.01);2组治疗后比较,治疗组中医症状积分、眼底积分低于对照组(P<0.05,P<0.01)。与本组治疗前比较,2组治疗后视力明显改善(P<0.05,P<0.01)。与本组治疗前比较,2组治疗后FPG、2 h PG、Hb Alc及TC、TG、LDL-C水平明显下降(P<0.01)。2组治疗后比较,治疗组2 h PG、Hb Alc及TC、TG、LDL-C水平低于对照组(P<0.05,P<0.01)。与本组治疗前比较,2组VEGF水平下降,PEDF水平提高,差异有统计学意义(P<0.01);2组治疗后比较,治疗组VEGF、PEDF改善优于对照组(P<0.05,P<0.01);VEGF、PEDF呈负相关(r=-0.320,P<0.01)。结论糖脂平方可有效改善NPDR患者的临床表现,通过降糖、降脂及调节血清VEGF、PEDF含量以减缓NPDR的病程进展。展开更多
OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropr...OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.展开更多
OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated...OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.展开更多
OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchu...OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.展开更多
目的从炎症小体活化和活性氧/硫氧还蛋白互作蛋白/NOD样受体蛋白3(ROS/TXNIP/NLRP3)通路考察牛舌草总黄酮(total flavonoids of Anchusa italica Retz.,TF)抗心肌缺血再灌注损伤的作用机制。方法小鼠采用冠状动脉左前降支结扎模型模拟...目的从炎症小体活化和活性氧/硫氧还蛋白互作蛋白/NOD样受体蛋白3(ROS/TXNIP/NLRP3)通路考察牛舌草总黄酮(total flavonoids of Anchusa italica Retz.,TF)抗心肌缺血再灌注损伤的作用机制。方法小鼠采用冠状动脉左前降支结扎模型模拟心肌缺血再灌注(ischemia/reperfusion,I/R)损伤。将模型制备成功的30只小鼠随机分为模型组(I/R)、TF 30 mg·kg^(-1)处理组(I/R+TF30)和100 mg·kg^(-1)处理组(I/R+TF100),再灌同时给予生理盐水、TF。于再灌注24 h时,检测小鼠心功能,测定心肌梗死范围和血清心肌酶谱,心肌冰冻切片染色观察活性氧(ROS)水平,Western blotting分析NLRP3炎症小体活化以及TXNIP与NLRP3相互作用的变化。结果TF在剂量为30和100 mg·kg^(-1)时均可改善心功能,减少心肌梗死范围,降低血清心肌酶水平。另外,TF处理减少心肌炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)α含量,降低心肌ROS水平。TF在30和100 mg·kg^(-1)均显著降低TXNIP、NLRP3、cleaved caspase-1和cleaved IL-1β,并抑制TXNIP/NLRP3相互作用。结论牛舌草总黄酮通过抑制ROS/TXNIP/NLRP3通路,从而减轻NLRP3炎症小体活化,发挥抗心肌缺血再灌注损伤作用。展开更多
文摘OBJECTIVE Here we investigated the effects and the underlying mechanism of Ginkgolide K(1,10-dihydroxy-3,14-didehydroginkgolide,GK)on cardiac ER stress.METHODS Cell death,apoptosis,and ER stressrelated signalling pathwayswere measuredin cultured neonatal rat cardiomyocytes(NRCMs),treated with the ER stress inducers tunicamycin,hydrogen peroxide,and thapsigargin.Acute myocardial infarction was established using left coronary artery occlusion in mice,and infarct size was measured by triphenyltetrazolium chloride(TTC)staining.Echocardiography was used to assess heart function and transmission electron microscopy for evaluating ER expansion.RESULTS GK significantly decreased ER stress-induced cell death in both in vitro and in vivomodels.In ischemic injured mice,GK treatment reduced infarct size,rescued heart dysfunction and ameliorated ER dilation.Mechanistic studies revealed that the beneficial effects of GK occur through enhancement of inositol-requiring enzyme 1α(IRE1α)/X box-binding protein-1(XBP1)activity,which in turn leads to increased ER-associated degradation(ERAD)-mediated clearance of misfolded proteins and autophagy.In addition,GK is also able to partially repress the pro-apoptotic action of regulated IRE1-dependent decay(RIDD)and JNK pathway.CONCLUSION GK acts through selective activation of the IRE1α/XBP1 pathway to limit ER stress injury.GK is revealed as a promising therapeutic agent to ameliorate ER stress for treating cardiovascular diseases.
文摘目的观察糖脂平方治疗非增殖期糖尿病视网膜病变(NPDR)的临床疗效及对血清血管内皮细胞生长因子(VEGF)和色素上皮衍生因子(PEDF)的影响。方法将86例NPDR患者随机分为治疗组和对照组各43例。2组均予降糖、降压、调脂基础治疗。对照组予羟苯磺酸钙胶囊,每次0.5 g,每日3次,口服;治疗组在对照组基础上予糖脂平方,每次1剂,每日2次,口服。均4周为1个疗程,连续治疗3个疗程。评价2组临床疗效及眼底疗效,观察中医症状积分、眼底积分、视力情况,检测空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及血清VEGF、PEDF含量变化。结果对照组与治疗组分别脱落2、3例。对照组临床疗效、眼底疗效总有效率分别为65.00%、68.35%,治疗组分别为87.50%、84.62%,2组比较差异有统计学意义(P<0.05)。与本组治疗前比较,2组治疗后中医症状积分、眼底积分明显下降(P<0.01);2组治疗后比较,治疗组中医症状积分、眼底积分低于对照组(P<0.05,P<0.01)。与本组治疗前比较,2组治疗后视力明显改善(P<0.05,P<0.01)。与本组治疗前比较,2组治疗后FPG、2 h PG、Hb Alc及TC、TG、LDL-C水平明显下降(P<0.01)。2组治疗后比较,治疗组2 h PG、Hb Alc及TC、TG、LDL-C水平低于对照组(P<0.05,P<0.01)。与本组治疗前比较,2组VEGF水平下降,PEDF水平提高,差异有统计学意义(P<0.01);2组治疗后比较,治疗组VEGF、PEDF改善优于对照组(P<0.05,P<0.01);VEGF、PEDF呈负相关(r=-0.320,P<0.01)。结论糖脂平方可有效改善NPDR患者的临床表现,通过降糖、降脂及调节血清VEGF、PEDF含量以减缓NPDR的病程进展。
基金The project supported by National Natural Science Foundation of China(81573645,81603101,81473383)
文摘OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.
基金The project supported by National Natural Science Foundation of China(81573645,81673422)
文摘OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.
基金CAMS Innovation Fund for Medical Sciences(CIFMS)318(2016-I2M-3-007)National Natural Science Foundation of China(81673422and 81202538)
文摘OBJECTIVE The plant of Anchusa italicahas been traditionally used in Uighur medicine for the treatment of cardiovascular and cerebrovascular diseases in China.Our previous study showed that total flavonoids from Anchusa italica(TFAI)exhibited potent cardioprotection on acute ischemia/reperfusion injured rats.This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction in mice and the underlying mechanism.METHODS Total flavonoids were extracted from the whole herb of Anchusa italica and were characterized using HPLC-MS analysis.The left anterior descending branch of coronary artery was ligated to induce myocardial infarction in mice.After surgery,the mice were orally fed with TFAI at the doses of 10,30 and 50 mg·kg-1 body mass per day for a total of four weeks.Cardiac function and infarct size were measured,and the levels of inflammatory mediators were detected.Hematoxylin and eosin(HE)stain and Masson Trichrome stain were performed.The apoptotic factors such as Bax,Bcl-2 and cleaved caspase 3 as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blotting.RESULTS The content of total flavonoids in TFAI was 56.2%.Four weeks following the MI surgery,TFAI enhanced the survival rate in post-MI mice.TFAI administration at the doses of 30 and 50 mg·kg-1 significantly reduced the infarct size and improved cardiac function indicated by elevated EF and FS.Assay of inflammation factors showed that the sera levels of TNF-α,IL-1β and IL-6 were significantly decreased by TFAI treatment as compared to the MI group.HE stain and Masson Trichrome stain demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis indicated by decreased cross-section area and collagen volume.Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were signifi⁃cantly downregulated following TFAI treatment.Additionally,TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.CONCLUSION TFAI exerts a protective effect against chronic myocardial infarction and its beneficial effects on cardiac function and cardiac remodeling might be at least attributable to anti-inflammation and suppression of the PI3K/Akt/mTOR signaling pathway.
文摘目的:通过观察连续4周给予复方利血平氨苯蝶啶片对自发性高血压大鼠(spontaneously hypertensive rat,SHR)的血压以及肠道菌群的影响,探讨其作用与肠道菌群调控之间的关系。方法:将40只SHR大鼠随机分为模型组(SHR)、培哚普利组(P)、复方利血平氨苯蝶啶片低剂量组(JL)和高剂量组(JH),另设10只Wistar大鼠为正常对照组(WKY)。各组均采取灌胃给药连续4周。每周测定并记录血压,末次给药后检测尿液钠离子、钾离子和血清醛固酮(aldosterone,Ald)含量;采集粪便提取大鼠肠道微生物总RNA,通过16SrRNA高通量测序对肠道菌群进行测序分析。结果:与SHR组相比,给药4周后JH组大鼠的收缩压和舒张压显著降低(P<0.05)。与SHR组相比,JL组和JH组大鼠血清醛固酮含量降低、尿液钠离子含量显著升高(P<0.05)。JL组、JH组及P组干预后菌群丰度与多样性增加。关联性分析显示,SHR大鼠血清醛固酮含量与乳酸细菌科(Lactobacillaceae)、厚壁菌科(unclassified p Firmicutes)等丰度显著相关,尿液中钠离子含量与氨基酸球菌科(Acidaminococcaceae)、萨特菌科(Sutterellaceae)等丰度显著相关。结论:复方利血平氨苯蝶啶片可改善SHR大鼠菌群丰度与多样性,促进毛螺旋科菌属、普雷沃科菌属、Muribaculaceae、Blautia等有益菌生长,抑制梭状芽孢杆菌属等有害菌增殖,对其发挥抗高血压作用具有重要意义。
