AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:M...AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:Male Wistar rats were randomly divided into three groups(36 rats each) :the sham-operation group(group S) ,lower limb ischemia-reperfusion group(group LIR) ,and penehyclidine hydrochloride postconditioning group(group PHC) .Each group was divided into subgroups(n=6 in each group) according to ischemic-reperfusion time,i.e.immediately 0 h(T1) ,1 h(T2) ,3 h(T3) ,6 h(T4) ,12 h(T5) ,and 24 h(T6) .Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h.In group PHC,0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia.The designated rats were sacrificed at different time-points of reperfusion;diamine oxidase(DAO) ,superoxide dismutase(SOD) activity,myeloperoxidase(MPO) of small intestinal tissue,plasma endotoxin,DAO,tumor necrosis factor-α(TNF-α) ,and interleukin(IL) -10 in serum were detected in the rats. RESULTS:The pathological changes in the small intestine were observed under light microscope.The levels of MPO,endotoxin,serum DAO,and IL-10 at T1-T6,and TNF-αlevel at T1-T4 increased in groups LIR and PHC(P<0.05) compared with those in group S,but tissue DAO and SOD activity at T1-T6 decreased(P<0.05) .In group PHC,the tissue DAO and SOD activity at T2-T6,and IL-10 at T2-T5 increased to higher levels than those in group LIR(P<0.05) ;however,the levels of MPO,endotoxin,and DAO in the blood at T2-T6,and TNF-αat T2 and T4 decreased(P<0.05) . CONCLUSION:Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR.Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.展开更多
Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplante...Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance, bone marrow mesenchymal stem cells were intramuscularly （gluteus maximus） injected with FK506 （tacrolimus） daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 ＋ bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 ＋ bone marrow mesenchymal stem cells group. The FK506 ＋ bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.展开更多
Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfu...Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.展开更多
Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism o...Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.展开更多
目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组...目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组大鼠夹闭股动脉缺血3h,再灌注3h;Sevo预处理+IR组(SIR组)吸入2.5%七氟烷30min,15min后制备肢体IR模型。实验结束后留取左肺,测定肺组织湿干/重比(W/D)和总肺水含量(TLW),光镜下观察肺组织病理学改变并测定肺组织损伤定量评估(IQA),电镜下观察肺组织超微结构改变,反转录-PCR(RT-PCR)和蛋白免疫印迹法(Western blot法)分别检测肺组织葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)的表达水平。结果与Sham组比较,IR组大鼠肺组织W/D、TLW和IQA均升高(P<0.05)。SIR组大鼠肺组织W/D、TLW和IQA均较IR组降低(P<0.05)。IR组大鼠肺组织形态学结构和超微结构发生明显损伤,而SIR组大鼠肺组织形态学结构和超微结构损伤均明显减轻。与Sham组比较,IR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均升高(P<0.05)。而SIR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均较IR组降低(P<0.05)。结论七氟烷预处理对肢体IR所致肺损伤发生的大鼠肺脏具有较好的保护作用,其机制可能与其抑制肺组织中过度的未折叠蛋白反应(UPR)有关。展开更多
基金Supported by Lanzhou City Development Plan of Science and Technology,No.2009-1-52
文摘AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:Male Wistar rats were randomly divided into three groups(36 rats each) :the sham-operation group(group S) ,lower limb ischemia-reperfusion group(group LIR) ,and penehyclidine hydrochloride postconditioning group(group PHC) .Each group was divided into subgroups(n=6 in each group) according to ischemic-reperfusion time,i.e.immediately 0 h(T1) ,1 h(T2) ,3 h(T3) ,6 h(T4) ,12 h(T5) ,and 24 h(T6) .Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h.In group PHC,0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia.The designated rats were sacrificed at different time-points of reperfusion;diamine oxidase(DAO) ,superoxide dismutase(SOD) activity,myeloperoxidase(MPO) of small intestinal tissue,plasma endotoxin,DAO,tumor necrosis factor-α(TNF-α) ,and interleukin(IL) -10 in serum were detected in the rats. RESULTS:The pathological changes in the small intestine were observed under light microscope.The levels of MPO,endotoxin,serum DAO,and IL-10 at T1-T6,and TNF-αlevel at T1-T4 increased in groups LIR and PHC(P<0.05) compared with those in group S,but tissue DAO and SOD activity at T1-T6 decreased(P<0.05) .In group PHC,the tissue DAO and SOD activity at T2-T6,and IL-10 at T2-T5 increased to higher levels than those in group LIR(P<0.05) ;however,the levels of MPO,endotoxin,and DAO in the blood at T2-T6,and TNF-αat T2 and T4 decreased(P<0.05) . CONCLUSION:Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR.Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.
基金the National Natural Science Foundation of China,No.30801171，the Natural Science Foundation of Hebei Province,No.C2009001013 and No.H2012406015
文摘Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance, bone marrow mesenchymal stem cells were intramuscularly （gluteus maximus） injected with FK506 （tacrolimus） daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 ＋ bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 ＋ bone marrow mesenchymal stem cells group. The FK506 ＋ bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.
文摘Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.
基金This study was supported by a grant from the Natural ScienceFoundation of Liaoning Education Committee (No.2004D193).
文摘Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.
文摘目的评价七氟烷(Sevo)预处理对大鼠肢体缺血/再灌注(IR)所致肺损伤的影响。方法健康成年清洁级Sprague-Dawley(SD)大鼠45只,采用随机数字表法分为3组(n=15):假手术组(Sham组)大鼠只分离股静脉和股动脉,但不夹闭;肢体缺血/再灌注(IR)组大鼠夹闭股动脉缺血3h,再灌注3h;Sevo预处理+IR组(SIR组)吸入2.5%七氟烷30min,15min后制备肢体IR模型。实验结束后留取左肺,测定肺组织湿干/重比(W/D)和总肺水含量(TLW),光镜下观察肺组织病理学改变并测定肺组织损伤定量评估(IQA),电镜下观察肺组织超微结构改变,反转录-PCR(RT-PCR)和蛋白免疫印迹法(Western blot法)分别检测肺组织葡萄糖调节蛋白78(GRP78)和CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)的表达水平。结果与Sham组比较,IR组大鼠肺组织W/D、TLW和IQA均升高(P<0.05)。SIR组大鼠肺组织W/D、TLW和IQA均较IR组降低(P<0.05)。IR组大鼠肺组织形态学结构和超微结构发生明显损伤,而SIR组大鼠肺组织形态学结构和超微结构损伤均明显减轻。与Sham组比较,IR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均升高(P<0.05)。而SIR组大鼠肺组织GRP78和CHOP m RNA及蛋白表达水平均较IR组降低(P<0.05)。结论七氟烷预处理对肢体IR所致肺损伤发生的大鼠肺脏具有较好的保护作用,其机制可能与其抑制肺组织中过度的未折叠蛋白反应(UPR)有关。
