Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule(通心络胶囊,TXL)on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocard...Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule(通心络胶囊,TXL)on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury(MIRI).Methods Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups:sham group,MIRI group,low-and high-dose TXL(0.5 and 1 g·kg^(-1)·d^(-1),respectively)groups,atorvastatin(ATV)group(7.2 g·kg^(-1)·d^(-1)),chloroquine(CQ)group(10 g·kg^(-1)·d^(-1)),and highdose TXL+CQ group.After pharmacological administration for 7 days,rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion.Blood was taken for cardiac troponin I(cTnI)detection and hearts were harvested for infarct staining and apoptosis detection.The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting.Results Compared with the sham group,the MIRI group exhibited a larger infarcted area(27.13%±0.01%,P<0.01),a higher apoptotic index(34.33%±2.03%vs.1.81%±0.03%,P<0.01),and higher cTnI expression(14.18±1.01 vs.7.96±0.32,P<0.01).The mitochondrial integrity was damaged in the MIRI group,while TXL and ATV alleviated the damage of MIRI.More autophagosomes were observed in the high-dose TXL group than in the MIRI group(7.00±0.58 vs.4.33±1.15,P<0.05).More amounts of PTEN-induced putative kinase protein 1(PINK1)and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group(P<0.05).The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group(P<0.05).CQ administration abolished the activation of autophagy flux and the PINK1/Parkin pathway induced by high-dose of TXL.Conclusions TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats.The downregulation of the ubiquitin-proteasome system is also involved.展开更多
This article presents the direct numerical simulation results of the turbulent flow in a straight square duct at a Reynolds number of 600, based on the duct width and the mean wall-shear velocity. The turbulence stati...This article presents the direct numerical simulation results of the turbulent flow in a straight square duct at a Reynolds number of 600, based on the duct width and the mean wall-shear velocity. The turbulence statistics along the wall bisector is examined with the turbulent flow field properties given by streamwise velocity and vorticity fields in the duct cross section. It was found that the solutions of the turbulent duct flow obtained in a spatial resolution with 1.2×10^6 grid points are satisfactory as compared to the existing numerical and experimental results. The results indicate that it is reasonable to neglect the sub-grid scale models in this spatial resolution level for the duct flow at the particular friction Reynolds number.展开更多
基金Supported by the National Basic Research Program(973 Program)of China(No.2012CB518601)。
文摘Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule(通心络胶囊,TXL)on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury(MIRI).Methods Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups:sham group,MIRI group,low-and high-dose TXL(0.5 and 1 g·kg^(-1)·d^(-1),respectively)groups,atorvastatin(ATV)group(7.2 g·kg^(-1)·d^(-1)),chloroquine(CQ)group(10 g·kg^(-1)·d^(-1)),and highdose TXL+CQ group.After pharmacological administration for 7 days,rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion.Blood was taken for cardiac troponin I(cTnI)detection and hearts were harvested for infarct staining and apoptosis detection.The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting.Results Compared with the sham group,the MIRI group exhibited a larger infarcted area(27.13%±0.01%,P<0.01),a higher apoptotic index(34.33%±2.03%vs.1.81%±0.03%,P<0.01),and higher cTnI expression(14.18±1.01 vs.7.96±0.32,P<0.01).The mitochondrial integrity was damaged in the MIRI group,while TXL and ATV alleviated the damage of MIRI.More autophagosomes were observed in the high-dose TXL group than in the MIRI group(7.00±0.58 vs.4.33±1.15,P<0.05).More amounts of PTEN-induced putative kinase protein 1(PINK1)and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group(P<0.05).The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group(P<0.05).CQ administration abolished the activation of autophagy flux and the PINK1/Parkin pathway induced by high-dose of TXL.Conclusions TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats.The downregulation of the ubiquitin-proteasome system is also involved.
基金supported by the National Natural Science Foundation of China (Grant No.10572135)the Research Grants Council of the Hong Kong Special Administrative Region,China (Grant No.PolyU5130/04E)
文摘This article presents the direct numerical simulation results of the turbulent flow in a straight square duct at a Reynolds number of 600, based on the duct width and the mean wall-shear velocity. The turbulence statistics along the wall bisector is examined with the turbulent flow field properties given by streamwise velocity and vorticity fields in the duct cross section. It was found that the solutions of the turbulent duct flow obtained in a spatial resolution with 1.2×10^6 grid points are satisfactory as compared to the existing numerical and experimental results. The results indicate that it is reasonable to neglect the sub-grid scale models in this spatial resolution level for the duct flow at the particular friction Reynolds number.
