The effect of melatonin on retinal apoptosis in rats with ischemia-reperfusion injury / 中华眼底病杂志

Objective To observe the effect of melatonin (MT) on retinal apoptosis in rats with ischemia-reperfusion injury (RIRI).Methods A total of 54 male healthy Sprague-Dawley adult rats were randomly divided into the normal control (CON) group (6 rats), RIRI group (24 rats) and MT group (24 rats). The rats of RIRI and MT group were induced using suture-occluded methods to establish RIRI model. The rats of MT group were injected with MT in the left carotid artery 30 minutes after RIRI, and RIRI group was injected with the same amount of saline. On 6, 24 hours and 3, 7 days after RIRI, the morphological changes of retina were evaluated by hematoxylin and eosin (HE) staining; the effects of MT on retinal cell apoptosis and Nrf2,HO-1 proteins were examined by immunohistochemistry staining. The correlation between active Caspase-3 and Nrf2 protein, active Caspase-3 and HO-1 protein in MT group were analyzed by linear regression analysis. Results HE staining results showed that the morphology of retinal cells was regular and retinal cells were well arranged in the CON and MT group. In the RIRI group, both the thickness of inner retinal layer and the number of retinal ganglion cells (RGC) were decreased. On 6, 24 hours and 3, 7 days after RIRI, the thickness of inner retinal layer (F=16.710, 62.303, 68.389, 57.132;P<0.01) and RGC number (F=24.250, 11.624, 14.155, 32.442;P<0.05) in MT group were more than those in RIRI group. Immunohistochemistry staining results showed that less active Caspase-3+ cells were observed in MT group as compared with those in RIRI group at each time points (F=49.118, 134.173, 76.225, 18.385;P<0.01). There were more Nrf2+ (F=11.041, 31.480, 59.246, 6.740;P<0.05) and HO-1+ cells (F=128.993, 21.606, 51.349, 8.244;P<0.05) in MT group as compared with those in RIRI group at each time points. Linear regression analysis results showed that the difference of active Caspase-3+cells were all linearly correlated with the Nrf2+ cells and HO-1+cells in the MT group (r2=0.810, 0.730;P<0.01). Conclusion MT could reduce retinal cell apoptosis in RIRI rats, and its mechanism may be associated with increased Nrf2 and HO-1 expression, reduced active Caspase-3 expression.

O impacto das soluções hipertônica e salina fisiológica na reperfusão do trato gastrintestinal pós-isquemia em ratos / The impact of hypertonic and normal saline in gut reperfusion after ischemia in rats

Objetivo: Investigar o papel de duas diferentes soluções salinas nos mecanismos de lesão após isquemia intestinal: estresse oxidativo e respostas inflamatórias. Métodos: Ratos Wistar foram submetidos a oclusão transitória da artéria mesentérica superior e estudados durante as 6 horas seguintes à reperfusão. Após randomização, os animais foram divididos em quatro grupos: Falso; Solução Hipertônica, os quais receberam infusão de solução salina hipertônica a 7,5% (4mL/kg de peso corpóreo); Solução Fisiológica, os quais receberam infusão de solução salina a 0,9% (33mL/kg); e Sem Tratamento. A infusão foi realizada imediatamente antes da reperfusão. Foram realizadas dosagens sequenciais de interleucina 6 e interleucina 10 no plasma. Foram coletadas amostras de tecidos (pulmão, fígado e intestino) para medir malondialdeído, mieloperoxidase e interleucina. Resultados: Em comparação ao Grupo Sem Tratamento, os animais que receberam volume (Grupos Solução Hipertônica e Solução Fisiológica) mostraram níveis tissulares mais baixos de malondialdeído, mieloperoxidase, interleucina 6 e interleucina 10. As concentrações plasmáticas de interleucina 6 e interleucina 10 foram mais altas nos animais tratados com solução hipertônica do que nos tratados com solução fisiológica e nos sem tratamento. Conclusão: Neste modelo de isquemia intestinal transitória, a manutenção adequada de volume intravascular diminuiu o estresse oxidativo e a síntese de marcadores de inflamação. Tanto a solução hipertônica quanto a fisiológica atenuaram os efeitos deletérios observados após isquemia intestinal. .

Objective: We investigated the effect of two different saline solutions on the mechanisms of injury after intestinal ischemia: oxidative stress and inflammatory responses. Methods: Wistar rats underwent transient superior mesenteric artery occlusion and were studied for 6 hours after reperfusion. After randomization, the animals were divided into four groups: Sham; Hypertonic Saline, in which they received infusion of 4mL/kg body weight of 7.5% hypertonic saline; Saline, in which they received infusion of 33mL/kg body weight of 0.9% saline; and Non Treatment. The infusion was performed immediately prior to the reperfusion. The plasma concentrations of interleukin 6 and interleukin 10 were measured. Tissue samples (lung, liver, and intestine) were collected for malondialdehyde, myeloperoxidase, and interleukin measurements. Results: The animals that received infusions (Hypertonic Saline and Saline) showed lower levels of tissue malondialdehyde, myeloperoxidase, interleukin 6, and interleukin 10 compared with the Non Treatment group. The plasma concentrations of interleukin 6 and interleukin 10 were higher in the animals treated with 7.5% hypertonic saline compared with Saline and Non Treatment groups. Conclusion: In this model of transient intestinal ischemia, the adequate maintenance of intravascular volume decreased oxidative stress and the synthesis of inflammatory markers. Both 7.5% Hypertonic Saline and Saline attenuated the deleterious effects observed after intestinal ischemia. .

The mechanism of alleviation of acute myocardial ischemia/reperfusion injury in rats by Fasudil / 中国医师杂志

Objective To explore the potential mechanism of Fasudil hydrochloride pharmacologic postconditioning that alleviated acute myocardial ischemia/reperfusion injury (MI/RI) in rats,narrowed the scope of infacted myocardium,and inhibited cell apoptosis.Methods Ninety rats were randomly and averagely divided into 5 groups:sham group,ischemia/reperfusion (I/R) group,ischemic postconditioning (IPost) group,fasudil hydrochloride (FH) group,and FH and PI3K inhibitor (LY294002) (FH + I) group.The expressions of Rho associated coiled-coil forming protein kinase-1 (ROCK-1),Bcl-2,Bax,Caspase-3,Akt,and P-Akt in rat myocardial cells were determined.Results Compared to I/R group (ROCK1:2.94 ± 0.13),ROCK1 expression was not changed in IPost group (ROCK1:2.79 ± 0.11),FH group (ROCK1:2.83 ± 0.10),and FH + I group (ROCK1:2.85 ± 0.26).Compared to I/R group (Bcl-2:1.11 ± 0.12,P-Akt:1.09 ± 0.06,Bax:1.74 ± 0.06,and caspase-3:1.32 ± 0.12),the expressions of Bcl-2 and P-Akt in FH group (Bcl-2:1.76 ± 0.08,and P-Akt:1.73 ± 0.05) and IPost group (Bcl-2:1.74 ± 0.06,and P-Akt:1.37 ± 0.05) were all significantly higher than those in I/R group (P ＜ 0.05),while the expressions of Bax and caspase-3 in FH group (Bax:0.98 ±0.14,and caspase-3:0.97 ±0.06) and IPost group (Bax:0.97 ±0.11,and caspase-3:1.07 ±0.08) were all significantly lower than those in I/R group (P ＜0.05).Compared to FH group,the expressions of Bcl-2 and P-Akt in FH + I group (Bcl2:1.05 ±0.12,and P-Akt:1.21 ±0.06) were decreased (P ＜0.05),while the levels of Bax and caspase-3 (Bax:1.61 ±0.11,and caspase-3:1.42 ± 0.11) were increased (P ＜ 0.05).Conclusions The mechanism of FH postconditioning was associated with the inhibition of ROCK activity,and the activation of PI3K-Akt pathway.

Protective effect of trimetazidine on myocardial ischemia/reperfusion injury in rats / 中国医师杂志

Objeetive To investigate protective effect of trimetazidine on myocardial ischemia/reperfusion injury (MIRI) in rats.Methods Forty Wistar rats were randomly divided into MIRI group (n =10 rats),trimetazidine high-dosage group (n =10 rats; 20 mg/kg),trimetazidine low-dosage group (n=10 rats; 10 mg/kg),and the normal control group (n =10 rats).After MIRI,hemodynamic changes were observed,the concentration of IL-6 and TNF-α was determined,and the cardiac muscle histology under the microscope was observed.Results Hemodynamic studies:Compared to the indices LVSP(198 ±35.5) mmHg,LVEDP (17 ±9.18) mmHg,+ dp/dt max (11050 ± 1517.4) mmHg/s,and-dp/dtmax (9175± 1900) mmHg/s] in the sham-operated group,the indices [LVSP (143 ± 24.5) mmHg,LVEDP (37.5 ±7.16)mmHg,+ dp/dtmax (7450 ± 1755.1) mmHg/s,and-dp/dtmax (6075 ± 1641) Hg/S] in the MIRI group,the indices [LVSP (154.5 ± 31.1) mmHg,LVEDP (31.3 ± 12.6) mmHg,± dp/dtmax (8527.7 ±2251.5) mmHg/s,and-dp/dtmax (6694 ± 2242.2) mmHg/s] in the trimetazidine low-dosage (10 mg/kg)group,the indices[LVSP (168.3 ± 17.6) mmHg,LVEDP (28 ± 10.05) mmHg,+ dp/dtmax (9213.6 ±1747) mmHg/s,and-dp/dtmax (7568 ± 1462.4) mmHg/s] in the trimetazidine high-dosage (20 mg/kg)group,left ventricular remodeling end diastolic pressure (LVEDP),left ventricular systolic pressure (LVSP),and left ventricular pressure maxial rate of rise and fall (± dp/dtmax) were significantly decreased.Compared to the MIRI group,LVSP and ± dp/dtmax in the trimetazidine high-dosage (20 mg/kg)group were significantly increased (P ＜ 0.01),and myocardial damage of MIRI group was more severe in microscope.Compared to the sham-operated group [IL-6 (2556.5 ± 662.9) ng/ml,and TNF-α (134 ± 73.7)ng/ml],the corresponding indices [IL-6 (3664.0 ± 995.7) ng/ml,and TNF-α (443 ± 22.1) ng/ml] in the MIRI group,[IL-6 (3692.8 1545.2) ng/ml,and TNF-α (295 ± 24.2) ng/ml] in the trimetazidiue low-dosage (10 mg/kg) group,and[IL-6(2654.8 ±681.7) ng/ml,and TNF-α(230 ±7.8) ng/ml]in the trimetazidine high-dosage (20 mg/kg) group,the levels of IL-6 and TNF-α were significantly increased.Compared to the MIRI group,the levels of IL-6 and TNF-α were significantly decreased in the trimetazidine high-dosage (20 mg/kg) group (P ＜ 0.01).Conclusions The high-dosage (20 mg/kg) of trimetazidine had a protective effect on myocardial ischemia-reperfusion injury.

Protective effects of Diemailing Injection on myocardial ischemia-reperfusion injury in rats / 吉林大学学报(医学版)

Objective To observe the protective effects of Diemailing Injection (DMLI) on myocardial ischemia-reperfusion injury in rats. Methods The myocardial ischemia-reperfusion model was induced by 30 min left anterior descending coronary occulusion and 24 h reperfusion in open-chest anesthetized rats. The changes of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), MB isoenzyme of creatine kinase (CK-MB), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) contents in serum, and prostacycline (PGI2) and thromboxane A2 (TXA2) levels in plasma were determined. Results In rats treated by DMLI (with dose of 2. 5, 5 and 10 mL ? kg-1 i. v. at 30 min after coronary occulusion), the myocardial ischemia size (MIS) was significantly reduced, the AST, LDH and CK-MB activities in serum and the TXA2 level in plasma were declined, while PGI2 level in plasma and PGI2/TXA2 ratio were increased significantly. In addition, the LPO content in serum declined, SOD and GSH-Px activities in serum were increased markedly. Conclusion DMLI has protective effects on myocardial ischemia-reperfusion injury through improving free radicals metabolism, decreasing TXA2 level in plasma, increasing PGI2 level in plasma and PGI2/TXA2 ratio.