BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and...BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.展开更多
Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats...Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO.Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry,histological changes (hematoxylin-eosin staining), Na+/K+-ATPase, Ca2+-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70)(quantitative real-time PCR).Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05),indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68,P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na+/K+-ATPase and Ca2+-ATPase reduced in the MCAO group (3.67±0.48 U/mg,1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65,P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group.Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.展开更多
Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (G...Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (GC) could reduce myocardial ischemia-reperfusion (IR) injury in rat heart. Methods: Twelve rats were randomized to IR group and GC group, then the hearts were isolated and perfused with Langendorff apparatus. Before cardioplegia, the perfusion was stopped abruptly in IR group while slowly with 5-minute in GC group. The hearts were subjected to 30-minute ischemia and 60-minute reperfusion. The left ventricular develop pressure (LVDP) and systolic pressure (LVSP), the maximal rate of the increase and decrease of left ventricular pressure (+dp/dt<sub>max</sub>, ﹣dp/dt<sub>max</sub>) were measured by polygraph system at different time points. The recovery of the variables was expressed as the ratio of these values at individual time point after reperfusion to the baseline respectively. Results: The recovery of LVDP after reperfusion was better than that in IR group (P = 0.034). No significant difference in the recovery of LVSP, +dp/dtmax and ﹣dp/dt<sub>max</sub> between groups was observed. Conclusions: Gradual clamping could improve the recovery of LVDP after IR, suggesting that gradual clamping could reduce myocardial IR injury.展开更多
MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis...MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.展开更多
BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infectio...BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infection and immunological rejection on bile duct injury. This study was undertaken to assess biliary tract injury caused by relative warm ischemia (secondary warm ischemia time in the biliary tract) and reperfusion. METHODS: One hundred and two rats were randomly divided into 5 groups: group I (control); groups 11 to V, relative warm ischemia times of 0 minute, 30 minutes, I hour and 2 hours. In addition to the levels of serum alkaline phosphatase, and total bilirubin, pathomorphology assessment and TUNEL assay were performed to evaluate biliary tract damage. RESULTS: Under the conditions that there were no significant differences in warm ischemia time, cold perfusion time and anhepatic phase, group comparisons showed statistically significant differences. The least injury occurred in group H (portal vein and hepatic artery reperfused simultaneously) but the most severe injury occurred in group V (biliary tract relative warm ischemia time 2 hours). CONCLUSIONS: Relative warm ischemia is one of the factors that result in bile duct injury, and the relationship between relative warm ischemia time the bile injury degree is time-dependent. Simultaneous arterial and portal reperfusion is the best choice to avoid the bile duct injury caused by relative warm ischemia. (Hepatobiliary Pancreat Dis Int 2009; 8: 247-254)展开更多
Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury ...Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.展开更多
[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中...[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。展开更多
本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(...本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(SOD和LDH),获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对灯盏甲素的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中灯盏甲素的PK-PD结合模型。当以SOD为药效指标时,可得辛芍组方中灯盏甲素的PK-PD模型为E=20.67+(1.22×Ce)/(Ce+5.58);当以LDH为药效指标时,可得辛芍组方中代表成分灯盏甲素的PK-PD模型为E=214.17-(32.72×Ce)/(Ce+0.08)。结果表明,SOD和LDH的浓度与灯盏甲素的浓度存在一定的相关性。辛芍组方及其主要活性成分灯盏甲素可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。展开更多
基金Liaoning Province Social Development Fund Sustentation Item, No. 99225003
文摘BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.
基金Fund supported by National Science Foundation of China (NSFC) 81503491,81374053, 81630105.
文摘Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO.Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry,histological changes (hematoxylin-eosin staining), Na+/K+-ATPase, Ca2+-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70)(quantitative real-time PCR).Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05),indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68,P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na+/K+-ATPase and Ca2+-ATPase reduced in the MCAO group (3.67±0.48 U/mg,1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65,P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group.Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.
文摘Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (GC) could reduce myocardial ischemia-reperfusion (IR) injury in rat heart. Methods: Twelve rats were randomized to IR group and GC group, then the hearts were isolated and perfused with Langendorff apparatus. Before cardioplegia, the perfusion was stopped abruptly in IR group while slowly with 5-minute in GC group. The hearts were subjected to 30-minute ischemia and 60-minute reperfusion. The left ventricular develop pressure (LVDP) and systolic pressure (LVSP), the maximal rate of the increase and decrease of left ventricular pressure (+dp/dt<sub>max</sub>, ﹣dp/dt<sub>max</sub>) were measured by polygraph system at different time points. The recovery of the variables was expressed as the ratio of these values at individual time point after reperfusion to the baseline respectively. Results: The recovery of LVDP after reperfusion was better than that in IR group (P = 0.034). No significant difference in the recovery of LVSP, +dp/dtmax and ﹣dp/dt<sub>max</sub> between groups was observed. Conclusions: Gradual clamping could improve the recovery of LVDP after IR, suggesting that gradual clamping could reduce myocardial IR injury.
文摘MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.
文摘BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infection and immunological rejection on bile duct injury. This study was undertaken to assess biliary tract injury caused by relative warm ischemia (secondary warm ischemia time in the biliary tract) and reperfusion. METHODS: One hundred and two rats were randomly divided into 5 groups: group I (control); groups 11 to V, relative warm ischemia times of 0 minute, 30 minutes, I hour and 2 hours. In addition to the levels of serum alkaline phosphatase, and total bilirubin, pathomorphology assessment and TUNEL assay were performed to evaluate biliary tract damage. RESULTS: Under the conditions that there were no significant differences in warm ischemia time, cold perfusion time and anhepatic phase, group comparisons showed statistically significant differences. The least injury occurred in group H (portal vein and hepatic artery reperfused simultaneously) but the most severe injury occurred in group V (biliary tract relative warm ischemia time 2 hours). CONCLUSIONS: Relative warm ischemia is one of the factors that result in bile duct injury, and the relationship between relative warm ischemia time the bile injury degree is time-dependent. Simultaneous arterial and portal reperfusion is the best choice to avoid the bile duct injury caused by relative warm ischemia. (Hepatobiliary Pancreat Dis Int 2009; 8: 247-254)
基金Supported by the National Natural Science Foundation of China(Nos.30700884,30873145)the Distinguished Middle-aged and Young Scientist Encourage and Reward Foundation of Shandong Province,China(No.BS2009SW015)
文摘Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
文摘[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。
文摘本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(SOD和LDH),获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对灯盏甲素的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中灯盏甲素的PK-PD结合模型。当以SOD为药效指标时,可得辛芍组方中灯盏甲素的PK-PD模型为E=20.67+(1.22×Ce)/(Ce+5.58);当以LDH为药效指标时,可得辛芍组方中代表成分灯盏甲素的PK-PD模型为E=214.17-(32.72×Ce)/(Ce+0.08)。结果表明,SOD和LDH的浓度与灯盏甲素的浓度存在一定的相关性。辛芍组方及其主要活性成分灯盏甲素可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。
