ABSTRACT
Ischemic stroke leads to high potentiality of mortality and disability.The current treatment for ischemic stroke is mainly focused on intravenous thrombolytic therapy.However,ischemia/reperfusion induces neuronal damage,which significantly influences the outcome of patients with ischemic stroke,and the exact mechanism implicated in ischemia/reperfusion injury remains unclear,although evidence shows that oxidative stress is likely to be involved.Betulinic acid is mainly known for its anti-tumor and anti-inflammatory activities.Our previous study showed that betulinic acid could decrease the reactive oxygen species (ROS) production by regulating the expression of NADPH oxidase.Thus,we hypothesized that betulinic acid may protect against brain ischemic injury in the animal model of stroke.Focal cerebral ischemia was achieved by using the standard intraluminal occlusion method and reperfusion enabled after 2 h ischemia.Neurological deficits were scored.Infarct size was determined with 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and the mRNA expression of NADPH oxidase 4 (NOX4) was determined by RT-PCR in infarct tissue.ROS generation and apoptosis in ischemic tissue were analyzed by measuring the oxidative conversion of cell permeable 2',7'-dichloro-fluorescein diacetate (DCF-DA) to fluorescent dichlorofluorescein (DCF) in fluorescence microplate reader and TUNEL assay,respectively.In Kunming mice,2 h of middle cerebral artery (MCA) occlusion followed by 24 or 72 h of reperfusion led to an enhanced NOX4 expression in the ischemic hemisphere.This was associated with elevated levels of ROS generation and neuronal apoptosis.Pre-treatment with betulinic acid (50 mg/kg/day for 7 days via gavage) prior to MCA occlusion prevented the ischemia/reperfusion-induced up-regulation of NOX4 and ROS production.In addition,treatment with betulinic acid could markedly blunt the ischemia/reperfusion-induced neuronal apoptosis.Finally,betulinic acid reduced infarct volume and ameliorated the neurological deficit in this stroke mouse model.Our results suggest that betulinic acid protects against cerebral ischemia/reperfusion injury in mice and the down-regulation of NOX4 may represent a mechanism contributing to this effect.
ABSTRACT
Acute kidney injury (AKI) is a common complication following orthotopic liver transplantation (OLT) and is associated with increased morbidity and mortality.The aim of the current study was to determine the risk factors for AKI in patients undergoing OLT.A total of 103 patients who received OLT between January 2015 and May 2016 in Tongji Hospital,China,were retrospectively analyzed.Their demographic characteristics and perioperative parameters were collected,and AKI was diagnosed using 2012 Kidney Disease:Improving Global Outcomes (KDIGO) staging criteria.It was found that the incidence of AKI was 40.8％ in this cohort and AKI was significantly associated with body mass index,urine volume,operation duration (especially ＞ 480 min),and the postoperative use of vasopressors.It was concluded that relative low urine output,long operation duration,and the postoperative use of vasopressors are risk factors for AKI following OLT.
ABSTRACT
Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP).Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry,but so far the mechanisms are poorly known.In this study,we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model.CIBP rats showed significant activation of microglia and astrocytes,and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β,IL-6,TNF-a and brain-derived neurotrophic factor) in the RVM.Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats' RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner.RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia,reversed the associated up-regulation of pro-inflammatory mediators and significantly attenuated mechanical allodynia.Taken together,these results suggest that RVM glial activation is involved in the pathogenesis of CIBP.RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators,which contribute to the descending facilitation of CIBP.
ABSTRACT
This study examined the analgesic effect of diprospan in rats with trigeminal neuralgia.Rat model of trigeminal neuralgic pain was established by loosely ligating the left infraorbital branch of the trigeminal nerve.After allodynia developed,the rats were randomly divided into 2 groups (n=20 in each):diprospan group,in which the rats received diprospan (7 mg/mL,0.1 mL) injected to the left infraorbital foramen area; control group,in which saline (0.1 mL) was administered as the same manner as the diprospan group.The pain threshold (PT) in the left infraorbital area was measured before and 2,6,and 8 weeks after the administration.The expression of neuropeptides [substance P,preprotachykinin A (PPTA),calcitonin gene-related peptide (CGRP)] in the trigeminal nerve was detected at the same time points as the PT measurement by immunohistochemistry or in siru hybridization method.The results showed that in the diprospan group,the PT was 10.65± 1.26,10.77± 1.19 and 14.13± 1.34 g 2,6,and 8 weeks after the administration respectively,significantly higher than that before the administration (PT value:0.36±0.11) (P＜0.05 for each).In the saline group,the PT was 0.37±0.13,0.66±0.09,4.45±1.29 and 13.72±1.72 g before and 2,6,and 8 weeks after the administration respectively with differences being significant between before and 6,8 weeks after the administration (P＜0.01).No significant difference existed in the PT between the diprospan group and the saline group at pre-administration (P＞0.05).The PT in the diprospan group was significantly greater than that in the saline group 2 and 6weeks post-administration (P＜0.05).In the diprospan group,the expression levels of neuropeptides were significantly reduced as compared with those in the saline group 2 and 6 weeks post-administration (P＜0.05).It was concluded that diprospan has an obvious analgesic effect on the trigeminal neuropathic pain partly by reducing the expression of neuropeptides in the trigeminal ganglia.