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Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.
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Pulmonary hypertension is a severe disease with a wide spectrum of underlying etiologies, which was characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, and eventually leads to right heart dysfunction and even death with a high mortality rate. Melatonin, as a neuroendocrine hormone, is produced primarily by the pineal gland. Melatonin, a pleotropic molecule, plays a key role in the pathophysiology of various cardiovascular diseases.The effects of melatonin which can attenuate pulmonary vascular remodeling and pulmonary artery pressure have been widely concerned by researchers in recent years. This review summarized the progress of melatonin on pulmonary hypertension.
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Objective To study the protective effect of erythropoietin (EPO) on brain tissue with cardiac arrest-cardiopulmonary resuscitation (CA-CPR) and its mechanism.Methods 120 male Sprague-Dawley (SD) rats were randomly divided into three groups (each n =40),namely:sham group,routine chest compression group,and conventional chest compression + EPO group (EPO group).The rats in each group were subdivided into CA and 6,12,24,48 hours after restoration of spontaneous circulation (ROSC) five subgroups (each n =8).The model of CA was reproduced according to the Hendrickx classical asphyxia method followed by routine chest compression,and the rats in sham group only underwent anesthesia,tracheostomy intubation and venous-puncture without asphyxia and CPR.The rats in EPO group were given the routine chest compression + EPO 5 kU/kg (2 mL/kg) after CA.Blood sample was collected at different time points of intervention for the determination the content of serum S100 β protein by enzyme linked immunosorbent assay (ELISA).All the rats were sacrificed at the corresponding time points,and the hippocampus was harvested for the calculation of the number of S100 β protein positive cells,and to examine the pathological changes and their scores at 24 hours after ROSC by light microscopy.Results With prolongation of ROSC time,the serum levels of S100 β protein (μg/L) in the routine chose compression group and the EPO group were significantly elevated,peaking at 24 hours (compared with CA:305.7 ± 29.2 vs.44.4 ± 6.2 in routine chest compression group,and 276.7±28.9 vs.44.7±5.6 in the EPO group,both P ＜ 0.05),followed by a fall.The levels of S100β protein at each time point after ROSC in EPO group were significanthy lower than those of the routine chest compression group (83.2 ± 7.5 vs.114.3 ± 15.3 at 6 hours,123.9 ± 20.2 vs.184.9 ± 22.2 at 12 hours,276.7 ± 28.9 vs.305.7 ± 29.2 at 24 hours,256.3 ± 26.6 vs.283.2 ± 23.6 at 48 hours,all P ＜ 0.05).With the prolongation of ROSC time,the S100 β protein positive cell number in brain (cells/HP) in the routine chest compression group and the EPO group was significantly increased,peaking at 24 hours (compared with CA:14.3±2.2 vs.6.7±0.7 in the routine chest compression group,11.3± 1.3 vs.6.8±0.9 in the EPO group,both P ＜ 0.05),then it began to fall.The S100 β protein positive cell number in brain at each time point after ROSC in the EPO group was significantly lower than that of the routine chest compression group (7.0±0.9 vs.7.9± 1.9 at6 hours,8.4± 1.1 vs.10.2±2.2 at 12 hours,11.3± 1.3 vs.14.3±2.2 at24 hours,8.3±0.8 vs.10.8±2.0 at48 hours,all P ＜ 0.05).Under the light microscope,a serious brain cortex injury was found after reproduction of the model,and the degree of injury was reduced after EPO intervention.The pathological score at 24 hours after ROSC in EPO group was lower than that of routine chest compression group (3.83±0.73 vs.4.17±0.75,P ＜ 0.05).Conclusions The S100β protein level in serum and brain tissue was increased early in asphyxia CA-CPR rats.EPO intervention can reduce the expression of S100 protein and reduce the degree of brain injury.
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BACKGROUND: Traditionally, cranial perforate-rinse-dram operation and tube drainage were often used in the treatment of chronic subdural hematoma in the elderly, recently,instead of which oxygen-exchange therapy through dural puncture via cranium is more and more used.OBJECTIVE: To investigate the reliability and safety of the new operation-method using oxygen-exchange in treating the older people with chronic subdural hematoma in comparison with traditional cranial perforate-rinse-dram operation.DESIGN: Retrospective case analysis.SETTING: The Department of Neurosurgery, the Second Clinical College of China Medical University.PARTICIPANTS: Eleven male patients (meanly 62 years of age)who had undertaken oxygen-exchange therapy via skull without drain tube in the Department of Neurosurgery, Second Clinical College of China Medical College from January 1997 to December 2004 were enrolled in the study, with an average disease history of 1.5 months. Among them, 10 subjects suffered from head injury to different extent within 7 weeks on average. Main chief complaint was headache, and Unilateral limb asthenia above Ⅳ was found in 5 cases asking for medical service. As shown by CT and MRI, all the subjects were diagnosed as having chronic subdural hematoma located at supratentorium, 5 cases in the right side and 6 in the left side. Volume of hematom was calculated as the following formula: volume of hematom=length×width×number of layers (1 cm thick for one layer). And the range of volume was from 70 mL to 140 mL, and the average value was 105 mL. The hematom in all the cases was found to move to the midline to different extents.METHODS: Patients in lateral recumbent position were undertaken boring at the CT-located thickest area with bone awl of 0.4-0.5 cm under local anesthesia. After boring, 14-size lumbar puncture needle with trochar was used to acupuncture dura mater then moving the needle core so that blood was discharged. Then 10 mL medical oxygen was perfused into the needle guard to cause the blood discharged from hematom again. Oxygen was perfused repetitively, once for 10 mL, till there was no blood flow. Finally, 10 mL oxygen was perfused following moving of trochar and bandaging.Oxygen volume used in each case was recorded. After operation,the volume of normal saline infusion could be increased as large as possible. The duration of infusion was 2 weeks.MAIN OUTCOME MEASURES: Improvement in limb function.RESULTS: All the patients were involved in the result analysis.①Within 24 hours, volume of hematomwas decreased obviously detected with CT, and hematom completely disappeared in 3 cases,which was replaced by oxygen. Three weeks later, all the oxygen was absorbed, the structure of midline was symmetrical and the form of brain ventricles was normal. No pain was found and 5 casesof limb asthenia were also recovered. ②Advantage and disadvantage of foramen-vertebrate oxygen-exchange operation: Advantages were listed as follows: It was simple and spent shorter time,there were few complications, and patients had no limitation in movement after operation. The operation avoided the occurrence of thrombosis of lower limbs. Cranial pressure could not lower quickly. As the pressure resident in envelope, cerebraospinal fluid could not move into the envelope. Along with the absorption of oxygen,hematom was decreased gradually till completely disappeared. Occurrence of clinical symptoms resulting from cerebral blood perfusion was decreased so as to draw rein. The disadvantage of this operation was that it was not suitable for heart disease patients to undertake this operation at bedside, and headache or limb asthenia could not be alleviated immediately.CONCLUSION: The new operation-method of cranial foramen-vertebrate oxygen-exchange to treat chronic subdural hemtoma in the elderly is safe, reliable and feasible through preoperative CT localization.