Quantification of DNA Damage in Different Tissues in Rats with Heart Failure / Quantificação de Dano em DNA em Diferentes Tecidos em Ratos com Insuficiência Cardíaca

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.

STRENGTH TRAINING AND ANABOLIC STEROID DO NOT AFFECT MUSCLE CAPILLARIZATION OF MIDDLE-AGED RATS / TREINAMENTO DE FORÇA E ESTEROIDE ANABOLIZANTE NÃO AFETAM A CAPILARIZAÇÃO MUSCULAR DE RATOS DE MEIA-IDADE / ENTRENAMIENTO DE FUERZA Y ESTEROIDE ANABOLIZANTE NO AFECTAN LA CAPILARIDAD MUSCULAR DE RATAS DE MEDIANA EDAD

ABSTRACT Introduction: It is generally accepted that the capillary network decreases with advancing age. The combined effect of resistance training (RT) and testosterone still needs to be elucidated. Objective: This study aimed to measure capillary profile of different skeletal muscles of middle-aged rats undergoing RT and administration of exogenous testosterone. Methods: Wistar rats were divided into five experimental groups: control with 13-month-old rats (SC), control with 16-month-old rats (SE), aged rats + anabolic agent (SA), aged rats + RT (T), and aged rats + RT + anabolic agent (TA). Results: For soleus, the SE group presented a decrease in the percentage of capillaries in comparison to SC group. SA, T, and TA groups had increased capillary volume in comparison to SC. As for the extensor digitorum longus (EDL), SA, T, and TA groups demonstrated lower capillary volume and numeric density in comparison to SC and SE. The EDL of the T and TA groups presented 70% less capillaries than soleus. The numerical and volumetric density and capillary ratio by muscle fiber were not statistically altered by any intervention. The cross-sectional area (CSA) of the soleus of the SA, T and TA groups was statistically different from SC group. The soleus CSA was greater in the TA and T groups than in the SC, SE and SA groups, and the EDL CSA was greater in the TA compared to all other groups. The TA group had greater values than the SE, SA, and T groups. Conclusion: The type of intervention used did not affect any variables measured in the capillary profile. However, the use of anabolic steroid and/or RT showed a tendency to decrease the density of capillaries in the EDL.

RESUMO Introdução: Em geral, se aceita que a rede capilar diminui com o avanço da idade. O efeito combinado de treinamento resistido (TR) e testosterona ainda precisa ser elucidado. Objetivo: Este estudo visou medir o perfil capilar de diferentes músculos esqueléticos em ratos de meia-idade submetidos a TR e administração de testosterona exógena. Métodos: Ratos Wistar foram divididos em cinco grupos experimentais: controle com ratos de 13 meses de idade (SC), controle com ratos de 16 meses de idade (SE), ratos idosos + anabolizante (SA), ratos idosos + TR (T) e ratos idosos + TR + anabolizante (TA) . Resultados: Para o músculo sóleo, o grupo SE apresentou decréscimo do percentual de capilares em comparação com o grupo SC. Os grupos SA, T e TA tiveram aumento do volume de capilares em comparação com o SC. Por outro lado, para o músculo extensor longo dos dedos (ELD), os grupos SA, T e TA demonstraram menor volume e densidade numérica de capilares, em comparação com SC e SE. O músculo ELD dos grupos T e TA apresentou 70% menos capilares do que o sóleo. A densidade numérica e volumétrica e a razão de capilares por fibra muscular não foram estatisticamente alteradas por nenhuma das intervenções. A área de corte transversal (ACT) do músculo sóleo dos grupos SA, T e TA foi estatisticamente diferente do grupo SC. A ACT do sóleo foi maior nos grupos TA e T do que nos grupos SC, SE e SA e a ACT do ELD foi maior no grupo TA comparada com todos os outros grupos. O grupo TA teve valores maiores do que os grupos SE, SA e T. Conclusão: O tipo de intervenção usada não afetou qualquer variável mensurada do perfil capilar. Entretanto, o uso de esteroide anabolizante e/ou TR mostrou tendência de diminuir a densidade de capilares no músculo ELD.

RESUMEN Introducción: Se acepta en general que la red capilar disminuye con la edad. El efecto combinado de entrenamiento de resistencia (ER) y la testosterona todavía necesita ser aclarado. Objetivo: Este estudio tuvo como objetivo medir el perfil capilar de diferentes músculos esqueléticos de ratas de mediana edad sometidas a ER y la administración de testosterona exógena. Métodos: Se dividieron ratas Wistar en cinco grupos: control con ratas de 13 meses de edad (SC), control con ratas de 16 meses de edad (SE), ratas de edad avanzada + anabolizantes (SA), ratas de edad avanzada + ER (T) y ratas de edad avanzada + ER + anabolizante (TA). Resultados: Para el músculo sóleo, el grupo SE mostró una disminución en el porcentaje de capilares en comparación con el grupo SC. Los grupos SA, T y TA presentaron aumento del volumen de capilares en comparación con el SC. Por otro lado, para el músculo extensor largo de los dedos (ELD), los grupos SA, T y TA mostraron menor volumen y menor número de capilares en comparación con los grupo SC y SE. El músculo ELD de los grupos T y TA presentó 70% menos capilares que el sóleo. La densidad numérica y volumétrica y la proporción de capilares por fibra muscular no se alteraron significativamente por ninguna de las intervenciones. El área de sección transversal (AST) del músculo sóleo de los grupos SA, T y TA fue estadísticamente diferente que el grupo SC. El AST del sóleo fue mayor en los grupos TA y T que en los grupos SC, SE y SA, y el AST del ELD fue mayor en el grupo TA en comparación con todos los demás grupos. El grupo TA tuvo valores más altos que los grupos SE, SA y T. Conclusión: El tipo de intervención utilizada no afecta a ninguna variable medida del perfil capilar. Sin embargo, el uso de esteroides anabolizantes y/o ER tendió a reducir la densidad capilar en el músculo ELD.

Mechanism research of chlorogenie acids on insulin resistance in nutritional obese rats / 重庆医学

Objective Study the effect of chlorogenie acids(CHA)on insulin resistance in obese rats induced by high‐fat diet . Methods We induced the obese rat model by feeding high‐fat diet ,obese rat model were divided into 4 groups:model group ,piogli‐tazone group(4 .5 mg/kg) ,CHA large dose group and group ,and finally determinated the levels of glucose tolerance ,serum insulin , serum lipid profiles and others .Results CHA showed a higher anti‐obesity activity with lower rate of increase of obese rats′body weights ,reversingglucose intolerance induced by high‐fat diet ,ameliorating the hyperinsulinemia ,decreaseing the levels of TG and TC ,and increase liver glycogen and muscle glycogen level compared with other group which treated with high‐fat diet .And in‐creased HOMA‐ISI ,decreased HOMA‐IR .Conclusion CHA can ameliorate the symptoms of insulin resistance in obese rats ,which mechanism may be related with CHA can stimulate glucose uptake and utilization by peripheral tissues ,and decrease the the serum levels of FFA ,decrease oxygen stress ,prevent and cure the injury induced by lipid peroxidation .

The effects of ET antisence oligoneuleotide and eNOS genetic transfection on the intimal hyperplasia of venouse autografts / 中国现代普通外科进展

Objective: To investigate the effects of endothelin(ET) antisence oligoneuceotide and nitric oxide synthase (NOS)genetic transfection on the intimal hyperplasia of venous autografts.Methods: The external jugule veins were autografted into abdominal aorta arteries in 20 Wistar rats, which were divided evenly into experimental and control group at random. The transplanted veins of experimental group were immersed in the adenovirus-mediated eNOS gene solution for 15 minutes just before anastomosis and coated with ET antisence olioneucleotide glue gel just after anastomosis, while the control ones were only immersed the physiologic saline for 15 minutes but nothing to be coated. The transplanted vascular samples were taken at 2 weeks after operation. The intimal thinkness (IH), degree of restenosis(DR), expression of PCNA, ETmRNA, NOS mRNA were determined by histology, transcription polymerase chain reaction.Results: The IH, DR and the expressions of ETmRNA were decreased while the expressions of eNOS mRNA was increased contrary to control group.Conclusion: Transfection of ET antisence oligoneuleotide and NOS gene can inhibit the intimal hyperlisia of venouse autogrfts,it is a prospective and idea genetic prophylactic therapy to intimal hyperplasia.

Evaluation of immune safety of application of enteral rehabilitative therapy in small bowel transplantation / 中国现代普通外科进展

Objective: To evaluate the safety of application of enteral rehabilitative therapy in small bowel transplantation.Methods: Forty-eight recipients of rat allogeneic heterotopic small bowel transplantation(SD→Wistar)were divided into 4 groups randomly according to the application or not of enteral rehabilitative therapy or cyclosporine A.The pathological changes of graft,IL-2 receptor expression of lamina propria lymphocyte,serum IL-2 concentration,transformation test of spleen lymphocyte and its IL-2 secretion capacity were determined and compared.Results: The enteral rehabilitative therapy may promote the immune function of recipient so to augment the acute rejection of small bowel transplantation.But such effects can be block by the common used immunosuppressant-cyclosporine A.Under the immunosuppression of CsA(10mg?kg -1 ?d -1 ,IM),application of enteral rehabilitative therapy can not induce or promote acute rejection of small bowel transplantation.Conclusion: Enteral rehabilitative therapy can augment the acute rejection of small bowel transplantation,but cyclosporine A can block its immunoenhancement effects.So under effective immunosuppression,application of enteral rehabilitative therapy is safe in small bowel transplantation.