RESUMO
To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)ï¼ the male SD rats were intraperitoneally injected with streptozotocin(STZï¼ 60 mg·kg⻹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)ï¼ the low-dose Nar group(Nar25)ï¼ the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25ï¼ Nar50ï¼ Nar100 groups were orally administered with Nar at the doses of 25.0ï¼ 50.0ï¼ 100.0 mg·kg⻹ per dayï¼ respectivelyï¼ while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatmentï¼ fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)ï¼ C/EBP homologous protein(CHOP)ï¼ cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the resultsï¼ compared with control groupï¼ the myocardial structure was damagedï¼ the content of MDA was increasedï¼ while the activities of SOD were decreased(P<0.05) in T1DR group. GRP78ï¼ CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(P<0.05ï¼ P<0.01). Compared with T1DR groupï¼ myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). After treatment with Nar for 8 weeksï¼ myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.
Assuntos
Cardiotônicos/farmacologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Flavanonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose , Caspase 12/metabolismo , Diabetes Mellitus Experimental , Proteínas de Choque Térmico/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Transcrição CHOP/metabolismoRESUMO
BACKGROUND: Serum testosterone levels have been found lower in acute ischemic stroke male patients. However, the exact mechanism remains unclear. In the present study, we measured serum testosterone levels, steroidogenesis- related genes and Leydig cells number in experimental transient cerebral ischemia male rats to elucidate the mechanism. METHODS: The middle cerebral arteries of adult male Sprague-Dawley rats were sutured for 120 minutes and then sacrificed after 24 hours. Blood was collected for measurement of serum testosterone, follicular stimulating hormone and estradiol levels, and testes were collected for measurement of steroidogenesis-related gene mRNA levels and number of Leydig cells. RESULTS: Serum testosterone levels in rats after cerebral ischemia were significantly lower (0.53 ± 0.16) ng/ml, n = 7, mean ± SE) compared with control ((2.33 ± 0.60) ng/ml, n = 7), while serum estradiol and follicular stimulating hormone levels did not change. The mRNA levels for luteinizing hormone receptor (Lhcgr), scavenger receptor class B member 1 (Scarb1), steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (Cyp11a1), 3ß-hydroxysteroid dehydrogenase 1 (HSD3ß1), 17α-hydroxylase/20-lyase (Cyp17a1) and membrane receptor c-kit (kit) were significantly downregulated by cerebral ischemia, while luteinizing hormone, Kit ligand (KitL), 17ß-hydrosteroid dehydrogenase 3 (HSD17ß3) and 5α-reductase (Srd5a1) were not affected. We also observed that, relative to control, the Leydig cell number did not change. CONCLUSIONS: These results indicate that transient cerebral ischemia in the brain results in lower expression levels of steroidogenesis-related genes and thus lower serum testosterone level. Transient cerebral ischemia did not lower the number of Leydig cells.