AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cer...AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cerebral ischemia-reperfusion was used. The activities of the two enzymes were measured by using biochemical methods. RESULTS DL -NBP and D -NBP 20 mg·kg -1 were found to significantly reduce ischemia ipsilateral cortical calcineurin and calpain activities. However, L -NBP 20 mg·kg -1 showed no obvious effect. CONCLUSION The anti-apoptotic effect of NBP may be relevant to its inhibition of calcineurin and calpain activities in focal cerebral ischemia rats.展开更多
Background Ischemic postconditioning （I-postC） is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion （I/R） injury. Endoplasmic reticulum ...Background Ischemic postconditioning （I-postC） is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion （I/R） injury. Endoplasmic reticulum （ER） is a principal site for secretary protein synthesis and calcium storage. Myocardial I/R causes ER stress and emerging studies suggest that the cardioprotection has been linked to the modulation of ER stress. The aim of the present study was to determine whether cardioprotection of I-postC involves reduction in ER stress through calcineurin pathway. Methods In the in vivo model of rat myocardial I/R, myocardial infarct size was measured by triphenyltetrazolium chloride （TTC） staining and apoptosis was detected using terminal eoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling （TUNEL） assay. Expression of calreticulin, C/EBP homologous protein （CHOP）, caspase-12, and activation of caspase-12 in myocardium were detected by Western blotting. The activity and expression of calcineurin in myocardium were also detected. Results I-postC protected the I/R heart against apoptosis, myocardial infarction, and leakage of lactate dehydrogenase （LDH） and creatine kinase-MB （CK-MB）. I-postC suppressed I/R-induced ER stress, as shown by a decrease in the expression of calreticulin and CHOP, and caspase-12 activation. I-postC downregulated calcineurin activation in myocardium subjected to I/R. Conclusion I-postC protects myocardium from I/R injury by suppressing ER stress and calcineurin pathways are not associated with the I-postC-induced suppression of ER stress-related apoptosis.展开更多
The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter...The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.展开更多
文摘AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cerebral ischemia-reperfusion was used. The activities of the two enzymes were measured by using biochemical methods. RESULTS DL -NBP and D -NBP 20 mg·kg -1 were found to significantly reduce ischemia ipsilateral cortical calcineurin and calpain activities. However, L -NBP 20 mg·kg -1 showed no obvious effect. CONCLUSION The anti-apoptotic effect of NBP may be relevant to its inhibition of calcineurin and calpain activities in focal cerebral ischemia rats.
基金This work was supported by the National Natural Science Foundation of China （No. 81070130 and 30770902）
文摘Background Ischemic postconditioning （I-postC） is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion （I/R） injury. Endoplasmic reticulum （ER） is a principal site for secretary protein synthesis and calcium storage. Myocardial I/R causes ER stress and emerging studies suggest that the cardioprotection has been linked to the modulation of ER stress. The aim of the present study was to determine whether cardioprotection of I-postC involves reduction in ER stress through calcineurin pathway. Methods In the in vivo model of rat myocardial I/R, myocardial infarct size was measured by triphenyltetrazolium chloride （TTC） staining and apoptosis was detected using terminal eoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling （TUNEL） assay. Expression of calreticulin, C/EBP homologous protein （CHOP）, caspase-12, and activation of caspase-12 in myocardium were detected by Western blotting. The activity and expression of calcineurin in myocardium were also detected. Results I-postC protected the I/R heart against apoptosis, myocardial infarction, and leakage of lactate dehydrogenase （LDH） and creatine kinase-MB （CK-MB）. I-postC suppressed I/R-induced ER stress, as shown by a decrease in the expression of calreticulin and CHOP, and caspase-12 activation. I-postC downregulated calcineurin activation in myocardium subjected to I/R. Conclusion I-postC protects myocardium from I/R injury by suppressing ER stress and calcineurin pathways are not associated with the I-postC-induced suppression of ER stress-related apoptosis.
文摘The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant.However,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense debate.The start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body.This variability seems to be correlated with the presence of genetic polymorphisms.Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given gene.However,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication.At present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of tacrolimus.However,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity.For these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.
