OBJECTIVE To determine the role of endogenous carbon monoxide(CO) in oxidant-mediated organ injury following limb ischemia-reperfusion (I/R) in rats. METHODS: Sixty-four SD rats were divided into 4 groups: Sham group, Sham + zinc protoporphyrin (ZnPP, an inhibitor of heme oxygenase activity), 2-hour ischemia followed by 4-hour reperfusion (I/R) group and I/R + ZnPP group. Carboxyhemoglobin (COHb) level in the artery blood, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung, heart, liver and kidney were detected. The 24-hour survival rate of rats was studied. RESULTS: Compared with the sham group, the COHb level and MDA content significantly increased, while the SOD activity and the survival rate significantly decreased in I/R group (P lt; 0.05). Compared with the I/R group, MDA content significantly increased, while the SOD activity, the 24-hour survival rate and COHb level significantly decreased in I/R + ZnPP group (P lt; 0.05, respectively). CONCLUSION: Limb I/R could lead to the oxidant-mediated multiple organ injury accompanied by the increase of CO level which play an important role in the defense against I/R-induced remote multiple organ injury in rats.
ObjectiveTo investigate the effect of basic fibroblast growth factor (bFGF) on expression of apoptosisrelated genes in retinal ischemiareperfusion injury (RIRI).MethodsTwentyeight rats were divided into normal, ischemia and treatment group randomly; and the latter two groups were subdivided into 6 subgroups according to different time points: 1 hour, 6, 12, 24, 48, and 72 hours after reperfusion. The rats′ model of experimental RIRI was established. After intravitreously injected with bFGF (treatment group) or balanced saline solution (ischemia group), the expressions of wide type p53 (WTp53)，c-fos, and c-jun in each subgroups were detected by streptavidinbiotin complex of immunohistochemistry.ResultIn ischemia group, the expression of WTp53,c-fos and c-jun was found 6 hours after reperfusion, reached the peak at the 24th hour after reperfusion, kept expressing bly at the 48th hour, and decreased obviously at the 72nd hour. In treatment group, the rule of changes of expression of WTp53, c-fos and c-jun was similar to which in ischemia group, except that the expression amount was obvious decreased. There was statistical significance of the expression of WTp53, c-fos and c-jun between the ischemia and treatment group 6-48 hours after reperfusion (P＜0.05）. ConclusionThe expression of WTp53,c-fos,and c-jun in retinal ganglion cell layer and inner nuclear layer may increase led by RIRI；WTp53,c-fos,and c-jun may be involved in the generant mechanisms of RIRI by playing parts in apoptosis；bFGF can inhibit the increase of expression of WTp53,c-fos,and c-jun in RIRI.Thus, which may has therapeutic effect on RIRI.( Chin J Ocul Fundus Dis,2005,21:310-313)
Objective To investigate the damage to the retinal cells and apoptosis of retinal cells of rats after ischemia-reperfusion insult. Methods The retinal ischemia-reperfusion model was developed by increasing intraocular pressure to 109725 mm Hg in rat eyes. Morphological changes of the rat eyes were observed by means of routine histopathology with HE staining. Apoptosis of the retina was assayed by both DNA fragmentation gel-electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL). Results Compared with the normal control, no histopathological changes were revealed in the rat retinas 30 min after the ischemia and then reperfued for 24 h or 48 h. Retinal ganglion cell layer (RGL) and inner plaxiform layer (IPL) of the retina were observed, however, to become significantly thinner 60 min after the ischemia and then reperfued for 24 h or 48 h. Together with the pathological changes DNA ladder pattern was detected in the same group of the rats. Further, immunochemical stain of the eye demonstrated that TUNEL positive cells were localized in RGL and IPL of the retina. Conclusion Ischemia-reperfusion insult of the eye may remarkably damage the retina of the rat eye. The damage to the retinal cells is mainly localized within RGL and IPL and apoptosis is the important mechanism of the retinal disorder. (Chin J Ocul Fundus Dis, 2002, 18: 296-298)
Objective:To observe the effect of beta;estradiol on gluta mate concentration in rabbitsprime; retinae injured by ischemic reperfusion. Methods:Twenty r abbits ware randomly divided into two groups, the control group and the treatmen t group, with 10 rabbits in each group. Before examined by binocular flash elect roretinography (FERG), retinal ischemic reperfusion (RIR) model was induced in t h e right eyes of all the rabbits by increasing intraocular pressure to 120 mm Hg for 60 minutes; the left eyes were as the control eyes. The rabbits were hypoder mically injected with beta;estradiol (0.1 mg/kg) in treatment group and with phys i ological saline in the control group 2 hours before ischemia. The results of FER G of the right eyes in both of the 2 groups 0, 4, 8, and 24 hours after reperfus ion were record respectively and were compared with the results of FERG before r eperfusion. The retina tissue was collected after the last time of FERG. The con c entration of glutamate was detected by Hitachi L8800 amino acid analyzer. Results:In the right eyes in both of the 2 groups, the result of F ERG showed a beeli ne just after reperfusion. There was no significant difference of awave amplit u de between the 2 groups (t=1.357, 0.798, 0.835; Pgt;0.05); the b wave amplitudes i n experimental group were much higher than those in the control group (t=4.447, 2.188, 3.106; Plt;0.01). The concentration of glutamate in retina was (0.265plusmn;0.014) g/L in the right eyes and (0.207plusmn;0.013) g/L in the left eyes in the control group, and (0.231plusmn;0.007) g/L in the right eyes and (0.203plusmn;0 .014) g/L in the le ft eyes in the treatment group; the difference between the 2 groups was signific ant (F=50.807, P=0.000). There was statistical difference between righ t and left eyes both in the 2 groups and the significant difference of the right eyes betw een the two groups was also found (P=0.000); there was no statistical diffe rence of the left eyes between the 2 groups (P＝0.505). Conclusion:beta;-estradiol may prevent the increase of the concentration of glutamate in retina induced by RIR to protect retinal tissue.
Exosomes are nanovesicles actively secreted by cells, which selectively encapsulate biologically active molecules such as proteins, RNA, and cytokines. They play an important role in intercellular communication, immune regulation, and maintenance of homeostasis, which can also be used as carriers for targeted drug delivery. Retinal ischemia-reperfusion injury (RIRI) is a retinopathy that seriously threatens human vision. At present, the clinical treatment of these diseases are symptomatic treatments, and some patients have poor efficacy or even blindness. As extracellular vesicles rich in functional proteins and RNAs, exosomes can not only be used as drugs for the treatment of RIRI, but also be used as carriers for drug delivery to play synergistic therapeutic effects. In the future, with the deepening of the research on the molecular structure, contents and biological functions of exosomes, as well as the continuous development of ophthalmic biology and genetic engineering technology, exosomes are expected to exert their great potential as therapeutic drugs and carriers, and become an important means of treating RIRI.
In order to study the influence of reperfusion following ischemia on microvesseles and microcirculation of skeletal muscle, unilateral hindlimbs of 16 rabbits were subjected to normothermic ischemia for 2 and 5 hours by tourniquet. After release of the tourniquet, microcirculation of the peritenon on dorsum of the foot was observed for 1 hours by intravital microscope. At 1 hour and 72 hours following reperfusion, the anterior tibia muscle biopsiy were taken and the specimens were subjected to light and electron microscopic examinations. It was found that after release of the tourniquet, in the limbs undergone 2 hours ischemia, there was immediate and well distributed reflow in the microvesseles of peritenon though a few aggregates of red cells and increase in the number of adherent leukocytes occured in some venules, and the microvesseles of the skeletal muscle only showed signs of minimal injury, the muscle fibers could survive in the limbs undergone 5 hours of ischemia, however, there was serious disturbance of microcirculation in theperitenon, which was characterized by "no reflow" in most area and there was signi ficant increase in the number of leukocytes adherent to venular endothelium, and the microvesseles of the skeletal muscle showed signs of severe injury, including remarkable swelling of the endothelial cell, disruption of the basement membrane and interstitial edema, and finally, most of the muscle fibers had necrosis occured. The results demonstrated that reperfusion following ischimia might result in microvascular injury and microcirculation disorder in the ischemic area. The degree of the injury and disorder depended on the duration of ischemic period, and was an important factor which determined the fate of the parenchymal cell.
Objective To evaluate the effectiveness of nicorandil for reperfusion of acute myocardial infarction (AMI), so as to provide high quality evidence for formulating the rational AMI therapy. Methods Databases including The Cochrane Library (Issue 3, 2012), PubMed, EMbase, HighWire, CBM, and CNKI were searched to collect randomized controlled trials (RCTs) on nicorandil in AMI reperfusion published before March 2012. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and evaluated the methodological quality of the included studies. Then the meta-analysis was conducted using RevMan5.1 software. Results A total of 11 trials involving 1 027 patients were included. The results of meta-analyses showed that: for AMI reperfusion, nicorandil could decrease the non-reflow or slow flow rate (RR=0.34, 95%CI 0.19 to 0.61, P=0.000 3), improve the left ventricular ejection fraction (MD=5.49, 95%CI 4.51 to 6.47, Plt;0.000 01), reduce the left ventricular end-diastolic volume (MD=–14.38, 95%CI –17.31 to –11.45, Plt;0.000 01), and decrease the incidence of cardiac adverse events (RR=0.34, 95%CI 0.25 to 0.46, Plt;0.000 01), readmission rate (RR=0.33, 95%CI 0.17 to 0.63, P=0.000 8) and mortality rate (RR=0.40, 95%CI 0.16 to 0.97, P=0.04). Conclusion Current evidence shows that nicorandil used as an adjuvant for AMI reperfusion can increase coronary microcirculation, improve prognosis, and decrease the incidence of cardiac adverse events, readmission and mortality rate. Due to the limited quality and quantity of the included studies, this conclusion still needs to be further proved by performing more large-scale and high quality RCTs, so we suggest clinician should adopt rational therapies based on patient’s conditions.
rough the ultramicroscopic observation on muscle and microcirculation, Group A,where a largeamount of DXM combined with heporin was given svstematically and locally into the femoral artery of the severed limb before replantation, and in Group B only heporin was given, and Group C and D ascontrol.The results showed that if the hormone and heparin were administred in large dosage, it wasadvantageous to reduce the tissues from reperfusion injury during delayed replantation.
Objective To explore the effect of ischemia-reperfusion injury on the retinal functions of rats. Methods Seventy Wistar rats were selected, 20 of which were selected randomly and divided into two groups (control group and single-irrigated group). The rats were anesthetized and their anterior chambers of the right eyes were cannulated with a 7-gauge needle connected to a reservoir containing ringers balanced salt solution, which was maintained at the same level o f the eye for 1 hour. After that, ERG was recorded in both eyes of all rats. All the left rats were divided randomly into 10 groups and they were treated as the single-irrigated group. Retinal ischemia was induced by raising the reservoir to a height of 150 mm Hg. One hour later except the single ischemia group, all o f t he groups resumed perfusion after 3,6,12,and 24 hours and 3,5,7,14,and 21 days s eparately. ERG was recorded in both eyes of all rats.Results There was no difference in the results of ERG between left and right eyes in either the control group or the single-irrigated group. All the waves of ERG vanished in the single-ischemia group after 1 hour. In the ischemia-reperfusion groups, the waves of ERG partly recovered and the amplitude reduced persistently and progressively.Conclusion Ischemia-reperfusion injury may affect the function of the retina persistently and progressively. (Chin J Ocul Fundus Dis，2003，19：201-268)
Objective To elucidate the protective effect of leukocyte depletion on the myocardium during the settings of myocardial reperfusion injury. Methods Twenty patients undergoing cardiopulmonary bypass with continuous infusion of blood cardioplegia were randomized into two groups:the control group (n=10) with no leukocyte depletion filter used, and the experimental group (n=10) with the use of leukocyte depletion filter on the bypass circuit. The blood cells count before and after the filtration were measure...