RESUMO
BACKGROUND/PURPOSE: Calycosin-7-O-ß-D-glucoside (CG), a calycosin derivative compound derived from Astragali Radix, has protective effect against ischemia/reperfusion injury as well as bacterial endotoxin-induced vascular cell injury. In the present study, we ascertained whether CG could reduce myocardial injury in heatstroke rats. METHODS: Heat stroke was induced by exposing anaesthetized rats to heat stress (43 °C for 70 min). Rats were given an i.p. dose of CG (26.8 mg/ml/kg) or vehicle solution (ml/kg) 15 min before the start of heat stress and immediately after termination of heat stress. Left ventricular performance, myocardial injury markers in the blood, and myocardial damage scores were assessed in heat stroke rats treated with or without CG. Additionally, cardiac levels of oxidative stress and inflammatory status were estimated simultaneously. RESULTS: At the time point of heat stroke onset, compared with normothermic controls, group rats with vehicle solution had significantly decreased survival rate, increased hyperthermia, decreased left ventricular stress markers, and increased cardiac damage scores. Compared with group rats with vehicle solution, group rats with CG had significantly improved survival rate, decreased hyperthermia, decreased cardiac ischemic, inflammatory, and oxidative damage. CONCLUSION: We thus conclude that myocardial injury can be a pressing need for the design of diagnostic and therapeutic modalities for heat stroke. In particular, our data indicate that CG protects against heat stroke in rats by mitigating myocardial injury.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Golpe de Calor/complicações , Isoflavonas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Astragalus propinquus , Medicamentos de Ervas Chinesas/química , Febre/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
High-mountain sickness is characterized by brain and pulmonary edema and cognitive deficits. The definition can be fulfilled by a rat model of high-altitude exposure (HAE) used in the present study. This study aimed to investigate the protective effect of hyperbaric oxygen therapy (HBO2T) and to determine the underlying mechanisms. Rats were subjected to an HAE (9.7% O2 at 0.47 absolute atmosphere of 6,000 m for 3 days). Immediately after termination of HAE, rats were treated with HBO2T (100% O2 at 2.0 absolute atmosphere for 1 hour per day for 5 consecutive days) or non-HBO2T (21% O2 at 1.0 absolute atmosphere for 1 hour per day for 5 consecutive days). As compared to non-HAE+non-HBO2T controls, the HAE+non-HBO2T rats exhibited brain edema and resulted in cognitive deficits, reduced food and water consumption, body weight loss, increased cerebral inflammation and oxidative stress, and pulmonary edema. HBO2T increased expression of both hippocampus and lung heat shock protein (HSP-70) and also reversed the HAE-induced brain and pulmonary edema, cognitive deficits, reduced food and water consumption, body weight loss, and brain inflammation and oxidative stress. Decreasing the overexpression of HSP-70 in both hippocampus and lung tissues with HSP-70 antibodies significantly attenuated the beneficial effects exerted by HBO2T in HAE rats. Our data provide in vivo evidence that HBO2T works on a remodeling of brain/lung to exert a protective effect against simulated high-mountain sickness via enhancing HSP-70 expression in HAE rats.
Assuntos
Doença da Altitude/terapia , Disfunção Cognitiva/terapia , Proteínas de Choque Térmico HSP70/genética , Oxigenoterapia Hiperbárica , Edema Pulmonar/terapia , Altitude , Doença da Altitude/genética , Doença da Altitude/metabolismo , Animais , Anticorpos/administração & dosagem , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Encefalite/metabolismo , Encefalite/fisiopatologia , Encefalite/terapia , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Pulmão/metabolismo , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/uso terapêutico , Edema Pulmonar/genética , Edema Pulmonar/metabolismo , Edema Pulmonar/fisiopatologia , RatosRESUMO
BACKGROUND Several clinical conditions can cause hepatic ischemia/reperfusion (I/R) injury. This study aimed to determine the mechanism of the protective effect of hyperbaric oxygen preconditioning (HBO2P) on hepatic ischemia/reperfusion (I/R) injury in a rat model, and to investigate the effects on HBO2P and I/R injury of blocking HSP70 using antibody (Ab) pretreatment. MATERIAL AND METHODS Male Sprague-Dawley rats underwent HBO2P for 60 min at 2.0 atmosphere absolute (ATA) pressure for five consecutive days before surgical hepatic I/R injury, performed by clamping the portal vein and hepatic lobe. Four groups studied included: the non-HBO2P+ non-I/R group, which underwent sham surgery (N=10); the non-HBO2P + I/R group (N=10); the HBO2P + I/R group (N=10); and the HBO2P + HSP70-Ab + I/R group (N=10) received one dose of HSP70 antibody one day before hepatic I/R injury. Serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) and myeloperoxidase (MPO) were measured biochemically. Rat liver tissues were examined histologically. RESULTS In rats with hepatic I/R injury without HSP70 antibody pre-treatment, HBO2P significantly reduced hepatic injury and levels of LDH, AST, ALT, TNF-α, IL-6, MDA, and MPO levels; in comparison, the group pre-treated with an antibody to inhibit HSP70 (the HBO2P + HSP70-Ab + I/R group) showed significant reversal of the beneficial effects of HBO2P on hepatic I/R injury (p<0.05). CONCLUSIONS In a rat model of hepatic I/R injury with HBO2P, HSP70 reduced hepatic inflammatory and oxidative damage.