Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left a...Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.展开更多
Association of Alzheimer's disease(AD) with cerebral glucose hypometabolism, likely due to impairments of insulin signaling,has been reported recently, with encouraging results when additional insulin is provided ...Association of Alzheimer's disease(AD) with cerebral glucose hypometabolism, likely due to impairments of insulin signaling,has been reported recently, with encouraging results when additional insulin is provided to AD patients. Here, we tested the potential effects of the anti-diabetic vanadium, vanadyl(IV) acetylacetonate(VAC), on AD in vitro and in vivo models. The experimental results showed that VAC at sub-micromolar concentrations improved the viability of neural cells with or without increased β-amyloid(Aβ) burden; and in APP/PS1 transgenic mice, VAC treatment(0.1 mmol kg-1 d-1) preserved cognitive function and attenuated neuron loss, but did not reduce brain Aβ plaques. Further studies revealed that VAC attenuated Aβpathogenesis by(i) activation of the PPARγ-AMPK signal transduction pathway, leading to improved glucose and energy metabolism;(ii) up-regulation of the expression of glucose-regulated protein 75(Grp75), thus suppressing p53-mediated neuronal apoptosis under Aβ-related stresses; and(iii) decreasing toxic soluble Aβ peptides. Overall, our work suggested that vanadyl complexes may have great potential for effective therapeutic treatment of AD.展开更多
基金This study was supported by Beijing University of Traditional Chinese Medicine Dongzhimen Hospital 2022 Science and Technology Innovation Special Project(DZMKJCX-2022-008)。
文摘Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.
基金supported by National Natural Science Foundation of China (21571006, 21771010)Beijing Municipal Science & Technology Commission (A61120-01)the "Strategic Priority Research Program" of the Chinese Academy of Sciences (XDA 12040101)
文摘Association of Alzheimer's disease(AD) with cerebral glucose hypometabolism, likely due to impairments of insulin signaling,has been reported recently, with encouraging results when additional insulin is provided to AD patients. Here, we tested the potential effects of the anti-diabetic vanadium, vanadyl(IV) acetylacetonate(VAC), on AD in vitro and in vivo models. The experimental results showed that VAC at sub-micromolar concentrations improved the viability of neural cells with or without increased β-amyloid(Aβ) burden; and in APP/PS1 transgenic mice, VAC treatment(0.1 mmol kg-1 d-1) preserved cognitive function and attenuated neuron loss, but did not reduce brain Aβ plaques. Further studies revealed that VAC attenuated Aβpathogenesis by(i) activation of the PPARγ-AMPK signal transduction pathway, leading to improved glucose and energy metabolism;(ii) up-regulation of the expression of glucose-regulated protein 75(Grp75), thus suppressing p53-mediated neuronal apoptosis under Aβ-related stresses; and(iii) decreasing toxic soluble Aβ peptides. Overall, our work suggested that vanadyl complexes may have great potential for effective therapeutic treatment of AD.
