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Ischemia-reperfusion (IR) is one of the significant medical problems in China. Triphenyltetrazolium chloride (TTC) stainingis used to detect the status of the infarct size, and real-time PCR and western blotting are used to detect expressions ofgenes. TUNEL assay has been used to detect apoptosis. Using a tree shrew myocardial IR model, we found that in thereperfusion period, resina draconis (RD) treatment reduced the infarct size by TTC staining, and significantly enhanced thesuperoxide dismutase expression and down-regulated the malondialdehyde concentration in a dose-dependent manner. Inhearts showing IR, Bax was increased and Bcl-2 was reduced, and RD treatment inhibited the IR-induced Bax expressionand up-regulated the IR suppressed level of Bcl-2. TUNEL assay showed that IR induced the apoptosis of myocardial cells,and RD treatment suppressed the IR-induced apoptosis. CHOP and GRP78 were also upregulated in IR hearts, and RDtreatment could significantly attenuate the CHOP and GRP78 levels compared with IR group. We further found that IRdecreased the miR-423-3p expression and upregulated its target gene ERK both in mRNA and protein levels, and RDtreatment upregulated miR-423-3p expression and downregulated ERK expression compared with the IR group. Importantly, miR-423-3p mimics inhibited IR increased ERK, CHOP and GRP78 expressions, and enhanced IR decreased Bcl-2expression, and inhibited the IR-induced apoptosis of myocardial cells. The findings of this study suggest that RD treatmentinhibited the endoplasmic reticulum induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signalingpathway in a tree shrew myocardial IR model.
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Objective: To detect and evaluate the hypothalamic infarction in middle cerebral artery occlusion (MCAO) model rat. Methods: For 15 Sprague-Dawley rats weighed 200-250 g, aged 6-8 months, their right middle cerebral artery was occluded for 90 min by a silicon-coated 4-0 nylon filament and reperfused. Sprague-Dawley rats underwent diffusion weighted MR imaging (DWI) scanning (at 1 h and 24 h after reperfusion) and 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining (at 24 h after reperfusion) to determine the hypothalamic and cerebral infarct volume. The relationship between hypothalamic infarct volume and cerebral infarction volume was analyzed by DWI scanning. The results of TTC staining were compared with those of 24 h DWI scanning. Results: Fifteen Sprague-Dawley rats successfully received intraluminal MCAO/reperfusion procedures. The incidences of hypothalamic infarction on brain DWI scanning and TTC staining were 100% and 40% at 24 h after reperfusion, respectively. Therefore, DWI scanning was more sensitive than TTC staining to detect hypothalamic injury (P=0.001). The hypothalamic infarct volume on DWI scanning was (8.59±2.89) mm3 and (11.65±3.19) mm3 at 1 h and 24 h after reperfusion, respectively. On DWI scanning, hypothalamic and cerebral infarct volume at 24 h after reperfusion were correlated with each other significantly (r=0.573, P=0.025), so were the increases of hypothalamic and cerebral infarct volume (r=0.554, P=0.032) from 1 h to 24 h. Conclusion: DWI scanning was more sensitive than TTC staining to detect hypothalamic injury in intraluminal transient MCAO model. Hypothalamic and cerebral infarct volume were correlated with each other.
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Objective To explore the influences of sufentanil and different dose midazolam coprocessing on myocardial injury in rats during myocardial ischemia-reperfusion (IR ). Methods Forty two healthy male SD rats were selected and randomly divided into 7 groups including,group A:rats were treated with sham operation;groups B0-B5:rat IR model was con-structed;group B0:rats were untreated with sufentanil or midazolam;group B1:rats were per-trea-ted with 3 μg/kg sufentanil;group B2:rats were post-treated with 0.1 mg/kg midazolam;group B3:rats were post-treated with 0.3 mg/kg midazolam;group B4:rats were per-treated with 1.5 μg/kg sufentanil and post-treated with 0.05 mg/kg midazolam;group B5:rats were per-treated with 1.5μg/kg sufentanil and post-treated with 0.15 mg/kg midazolam.Sufentanil was injected through cervi-cal vein before ischemia.Midazolam was injected through cervical vein after ischemia.After reperfu-sion,arterial blood was collected for detecting the activity of CK-MB,LDH or SOD,and the concen-tration of MDA,TNF-α,or IL-6.Rat hearts were picked off to measure the severity of myocardial in-farction (IS/AAR).The expressions of Bax,cleaved-caspase-3 and Bcl-2 in myocardial tissues were detected by Western blots.Results CK-MB activity,LDH activity,MDA concentration,TNF-αlev-el,IL-6 level,Bax and cleaved-caspase 3 expression levels in groups B0-B5 were obviously higher than those in group A (P <0.05),in groups B1-B5 were obviously lower than those in group B0 (P<0.05),in groups B3 and B4 were obviously lower than those in group B2 (P <0.05),in group B5 were obviously lower than those in groups B1-B4 (P < 0.05 );values of IS and IS/AAR (%)in groups B1-B5 were obviously lower than those in group B0 (P <0.05),in groups B3 and B4 were ob-viously lower than those in group B2 (P < 0.05 ),in group B5 were obviously lower than those in groups B1-B4 (P <0.05 );SOD activity and Bcl-2 expression level in groups B0-B5 were obviously lower than those in group A (P <0.05),in groups B1-B5 were obviously higher than those in group B0 (P <0.05),in groups B3 and B4 were obviously higher than those in group B2 (P <0.05 ),in group B5 were obviously higher than those in groups B1-B4 (P <0.05).CK-MB declined when com-pared with group B0;LDH declined;SOD rose;MDA declined;TNF-αdeclined;IL-6 declined;IS/AAR declined;Bcl-2 expression rose to 2.25 fold;Bax expression dropped to 54.89%;cleaved-caspase-3 expression dropped to 49.67%.Conclusion Sufentanil pretreatment combined with mid-azolam aftertreatment can significantly alleviate rat myocardial IR injury,which plays more effective cardioprotective effects than being used alone.
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The present study aimed to explore the effects of Eerdun-Wurile on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expressions in the prefrontal cortex of MCAO / R injury rats.Sixty SD male rats of SPF grade were selected to establish the model of MCAO / R with Zea-Longa thread occlusion,and divided into five groups at random:the sham operation group,the model group,the nimodipine group and the Eerdun-Wurile group.After modeling,rats were anesthetized for preparing the brains.The pathomorphological changes of the brains were evaluated by immunohistochemical techniques,such as HE staining and SP.The protein and mRNA expressions of BDNF and NGF in the prefrontal cortex of rats were detected by ELISA and RT-PCR,respectively.As a result,compared with the model group,it was found that the number of necrotic cells in the prefrontal cortex were significantly reduced in the Eerdun-Wurile group (P ＜ 0.05),while the mRNA and protein expressions of BDNF and NGF were significantly increased (P ＜ 0.05).In conclusion,the BDNF and NGF expressions in the prefrontal cortex were up-regulated for stimulating the activation of astrocytes and protecting the neurons with the treatment of Eerdun-Wurile in MCAO / R injured rats,which may be the mechanism of the treatment of Eerdun-Wurile for white vein disease.
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@#The purpose of this research was to study the effect of Xingxiong sodium chloride injection on cerebral ischemia-reperfusion injury in rats. Rats were divided into five groups, namely sham group, model group, ginkgolide injection group(3 mg/kg), Xingxiong sodium chloride injection high-dose group(14 mg/kg)and low dose group(7 mg/kg). Except for the sham group, animals in other groups were subjected to ischemia for 2h and reperfusion for 72 h by middle cerebral artery occlusion(MCAO)with thread technique, and then drugs were administered continuously by tail intravenous injection during reperfusion period for 3 days. The neurological deficit score and the histopathological score were evaluated; infarction ratio, brain water content and biochemical indexes of animals in each group were determined. Compared with model group, reduction of neurological deficit score, brain water content and infarction area were observed obviously at 7 mg/kg and 14 mg/kg of Xingxiong sodium chloride injection. Additionally, reduction of histopathological score, H2O2 and MDA content, increase of the level of GSH, GSH-Px, SOD and also the capacity of inhibition of superoxide anion radical(·O-2)and hydroxyl radial(·OH)were observed at 14 mg/kg. The results suggested that Xingxiong sodium chloride injection could effectively enhance the ability of anti-oxidation in the brain tissues, and protect brain from ischemia-reperfusion injury.
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Objective To observe the effect of estrogen on BBB permeability,occludin expression after ischemia-reperfusion in rats,and to make a further investigation on the role of estrogen in cerebral ischemia. Methods Ovariectomized rats were randomly divided into sham-operated group,model group,and estrogen pretreatment group. 4 h,24 h,3 d after ischemia-reperfusion were selected as different observation points,and changes of edema,occluding expression,and blood-brain barrier permeability of the 3 points in time were observed. BBB ultra-structure electron microscope observation was made at 24 h and 3 d after ischemia-reperfusion. Changes in cerebral edema were measured by brain water content percentage;protein expressions were measured by Western blot;and BBB permeability was measured by Evans blue as-say. Results Compared with the sham group,brain tissue water content and EB content in model group both increased 4 h after ischemia-reperfusion (P0. 05). 24 h after ischemia-reperfusion,the occludin expression were weaker than that in the sham surgery group with a significant difference (P0. 05). In estrogen group,there was significant difference in occludin protein expression at 24 h and 3 d after ischemia-reperfusion compared with model group at the same time point (P<0. 05). Conclusion BBB ultrastructure disclose TJ was broke and vesicles within EC was increased and astrocyte cell foot process was swelling in MCAO model,it might be the vasogenic brain edema pathological basis for MCAO. In MCAO animal model,with ischemia-reperfusion time increasing,TJ protein occludin expression significantly decreased,it suggests that occludin plays an important role in the regulation of TJ permeability. Estrogen increases has a very close relationship with occludin ex-pression,and it may be one of the mechanisms of protecting BBB integrity and lessening cerebral edema.
ABSTRACT
Reducing the infarct size in acute myocardial infarction is one of the most important goals driving new drug research and development. During the last two decades, many clinical studies have found cardioprotective effects of corticosteroids, but their exact role in ischemic preconditioning remains questionable. The aim of the present study was to determine the protective effects of hydrocortisone sodium succinate on myocardial preconditioning in rabbit hearts. Twenty-four male New Zealand rabbits were divided randomly & equally in four groups: 1) control, 2) Infarct, 3) Ischemic preconditioning (IP) and 4) Hydrocortisone (HYD). The HYD group received 50mg/kg Hydrocortisone 45min before major ischemia. Serum levels of cardiac troponin-T(cTNT) and cortisole were measured before and after the protocols. Triphenyl-tetrazolium chloride staining was used to determine the infarcted area. In the present study, exogenous hydrocortisone decreased infarct size by 53 percent in comparison to the infarct group. Serum level of cortisole was increased in the IP and HYD groups, and was significant in the HYD group (p<0.01). An increasing trend in cortisole level was associated with a decreasing trend in infarct size and cTNT in the IP and HYD groups (p>0.01). In conclusion, we showed that hydrocortisone has cardioprotective effects when injected before the onset of myocardial infarction. In addition, we have proposed for the first time that endogenous hydrocortisone may play a role in ischemic preconditioning phenomena.
La reducción del tamaño del infarto en el infarto agudo de miocardio es una de las metas más importantes que impulsan la investigación y el desarrollo de nuevos fármacos. Durante las dos últimas décadas, muchos estudios clínicos han encontrado efectos cardioprotectores de los corticosteroides, pero su papel exacto en el preacondicionamiento isquémico sigue siendo cuestionable. El objetivo del presente estudio fue determinar los efectos protectores de succinato sódico de hidrocortisona en el preacondicionamiento del miocardio en el corazón de conejo. Veinticuatro conejos neozelandeses machos fueron divididos al azar en cuatro grupos : 1) control, 2) infarto, 3) preacondicionamiento isquémico (PI) y 4) Hidrocortisona (HYD). El grupo HYD recibió 50 mg/kg de hidrocortisona 45 minutos antes de la isquemia mayor. Los niveles séricos de troponina cardíaca T (cTNT) y cortisol se midieron antes y después de los protocolos. Se utilizó la tinción cloruro de trifenil-tetrazolio para determinar el área infartada. En el presente estudio, la hidrocortisona exógena disminuyó el tamaño del infarto en un 53 por ciento en comparación con el grupo de infarto. Los niveles séricos de cortisol se incrementaron en los grupos IP y HYD, siendo significativa en el grupo de HYD (p <0,01). Un aumento en el nivel cortisol se asoció con la disminución del tamaño del infarto y la cTNT en los grupos IP y HYD (p> 0,01). En conclusión, hemos demostrado la hidrocortisona tiene efectos cardioprotectores cuando se inyecta antes de la aparición del infarto al miocardio. Además, hemos propuesto, por primera vez que la hidrocortisona endógena puede jugar un papel en los fenómenos de preacondicionamiento isquémico.