Effects of early phase of preconditioning on rat testicular ischemia

INTRODUCTION: Brief episodes of ischemia followed by periods of reperfusion generate a powerful protective mechanism in cell, tissue or organ, which increase the resistance to further ischemic damage. This is known as ischemic preconditioning, and has not been investigated in testis. The present experiments were undertaken to determine whether early phase of ischemic preconditioning is evident in rat testis. MATERIALS AND METHODS: Surgery was conducted under thiopental (60 mg/kg, intraperitoneal) anesthesia in male Wistar rats. Surgical procedures were performed through a midline incision. Group 1 was designed as a sham group. In group 2, which served as the ischemia group, the animals were subjected to unilateral testicular torsion by rotating the left testis 720 degrees in a clockwise direction. Then, this testis was maintained in the torsion position by fixing with a silk suture to the scrotal wall for 90 min. In groups 3 and 4, 5 or 10 min ischemia followed by 10 min reperfusion was introduced, respectively, to induce single cycle ischemic preconditioning. In group 5, which served as the multiple cycle preconditioning group, 3 cycles of 10 min ischemia and 10 min reperfusion were applied prior to 90 min ischemia. Both ipsilateral and contralateral testes were removed from the rats at the end of the experimental periods, and tissue malondialdehyde (MDA), nitric oxide (NO) levels, xanthine oxidase (XO), myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were measured. Both testes were also evaluated histologically, assessing interstitial edema, congestion, hemorrhages, rupture of tubules and Leydig cell proliferation. RESULTS: 90 min ischemia produced a marked increase in MDA level in left testis. However, all ischemic preconditioning protocols used in this study did not show any significant modification in MDA, NO levels or XO, MPO and SOD activities. Histological grading scale was also similar in ischemia and preconditioning groups. CONCLUSION: These results suggest that there are no protective effects with ischemic preconditioning in rat testis as showed by biochemical analysis and histological examinations.     

低温联合地塞米松对大鼠睾丸扭转复位后eNOS表达及生精细胞凋亡的影响

目的:探讨低温联合地塞米松对睾丸扭转复位后的保护作用,以及对eNOS表达及生精细胞凋亡的影响。方法:将80只青春期SD大鼠随机分为4组,每组20只。4组大鼠分别扭转左侧睾丸720°2 h,建立单侧睾丸扭转模型,随后各组做如下处理,A组:常温+生理盐水、B组:低温+生理盐水、C组:低温+地塞米松、D组:常温+地塞米松;术后48 h采集睾丸,通过HE染色光镜观察睾丸组织病理学改变、免疫组化法检测eNOS表达、TUNEL法检测睾丸生精细胞凋亡。结果:HE染色光镜下见4组大鼠扭转侧睾丸组织均有不同程度损伤,其中A组睾丸损伤最明显,其余3组扭转侧睾丸得到不同程度保护;睾丸组织eNOS免疫组化检测结果:A组扭转侧(左侧)睾丸组织阳性细胞数及阳性细胞着色强度明显强于B、C、D 3组,差异具有显著性(P<0.05、P<0.01、P<0.01);凋亡细胞染色:细胞核呈深棕黄色或棕褐色,A组扭转侧(左侧)睾丸可见大量生精细胞凋亡,凋亡指数AI(31.12±4.68)明显高于B组(16.58±6.22)(P<0.05)及C(8.60±1.15)、D组(13.52±3.06)(P<0.01)。结论:睾丸扭转复位后的缺血再灌注损伤可导致生精细胞凋亡增加、睾丸生殖能力下降;应用低温联合地塞米松能显著增强睾丸组织的抗损伤能力,较好地保护了扭转复位后睾丸的生精功能。     

延迟性低温复合巴曲酶对沙土鼠全脑缺血后神经的影响

目的 研究短暂全脑缺血后３０分开始的低温复合巴曲酶对沙土鼠行为学和组织病理学的影响。方法 采用沙土鼠全脑缺血模型,缺血时间１０分,动物随机分为５组,假手术组,常温组,延迟性低温组,巴曲酶组,延迟性低温复合巴曲酶组,每组７只,低温（３２℃）于再灌注３０分给予,维持３小时,巴曲酶８ＢＵ．ｋｇ＾－１再灌注３０分经腹腔注入,于动物存活第５天行开阔法行为学检查,第７天行海马ＣＡ１我组织病理学检查,结果 行为     

Protective effect of hypothermia in cerebral ischemia]

The use of hypothermia to protect the brain from ischaemic insults is an old concept. During the last decades, studies have mainly shown a modulating effect of hypothermia on biochemical cerebral responses to ischaemia, in addition to the basic effect of energy savings. Thus, the beneficial effects of decreased brain temperature, even when limited during transient ischaemic insults, whether global or focal, complete or incomplete, have been established. The deeper the hypothermia, the longer the ischaemia can be prolonged with acceptable neurological outcome. Conversely, the effects of postischaemic hypothermia remain unclear, while extracerebral deleterious effects cannot be overlooked, and many parameters remain to be evaluated before undertaking a beneficial clinical trial. The only indication for therapeutic postischaemic hypothermia in the near future could be in the control of impending intracranial hypertension occurring after cerebral ischaemia.     

Effects of intrathecal bupivacaine in conjunction with hypothermia on neuronal protection against transient spinal cord ischemia in rats

BACKGROUND: Excitotoxic neuronal injury from ischemia may be reduced by local anesthetics. We investigated the neuroprotective effects of intrathecally administered bupivacaine and hypothermia in a rat model of transient spinal cord ischemia. METHODS: PE-10 intrathecal catheter-implanted male Sprague-Dawley rats were randomly assigned to one of four groups: normothermia (NT) and hypothermia (HT) groups (given 15 microl of normal saline) and bupivacaine (B) and bupivacaine-hypothermia (BHT) groups (given 15 mul of 0.5% bupivacaine). Transient spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed in the aortic arch for 12 min. The rectal temperature was maintained at 37.0 +/- 0.5 degrees C for the NT and B groups, and at 34.5 +/- 0.5 degrees C for the HT and BHT groups. Motor and sensory deficit scores were assessed 2 and 24 h after reperfusion. Lumbar spinal cords were harvested for histopathology and immunoreactivity of heat shock protein 70 (HSP70). RESULTS: After reperfusion, the motor and sensory deficit scores of the NT group were significantly higher than those of the HT (P < 0.05) and BHT (P < 0.001) groups. Significant differences were evident in the motor and sensory deficit scores between the HT and BHT groups at 24 h (P < 0.05). Neuronal cell death and immunoreactivity of HSP70 were frequently observed in the NT and BT groups, but not in the HT and BHT groups. CONCLUSIONS: These results collectively suggest that intrathecal bupivacaine does not provide neuroprotection during normothermic transient spinal cord ischemia in rats, but enhances the neuroprotective effects of hypothermia.     

Effects of chemotherapy on testicular functions

Of 26 previously normospermic patients treated with MOPP (nitrogen mustard, vincristine, procarbazine and prenisone) for Hodgkin's disease, 22 had azoospermia, 2 had severe oligozoospermia below 0.1 times 10⁶ spermatozoa/ml, 2 had 5 times 10⁶ spermatozoa/ml. Follicle stimulating hormone (FSH) increased significantly in all but 2 patients, but the luteinizing hormone (LH) increase was not significant. Prolactin, testosterone and 17β-oestradiol levels were unmodified. Chemotherapy is widely used for malignant and non-malignant diseases, the various drugs having different levels of toxicity. In order to prevent male sterility as a result of chemotherapy, the physician must choose the therapeutic agents carefully and may recommend cryopreservation of the patient's semen prior to therapy. In addition, the minimize the hazards of chemotherapy, the testis may be cooled during drug infusion and the germinal epithelium may be put to rest by desensitization through a LH releasing hormone analog.     

线粒体介导的凋亡途径与浅低温脑保护效应

低温有明显的神经保护作用,但其确切的作用机制尚未阐明。凋亡参与了缺血性脑损伤,且加重损伤程度。线粒体在凋亡过程中的作用越来越受到重视,多种促和抗凋亡因素作用于线粒体,引发线粒体功能和生化方面的改变,决定细胞损伤后的命运。最近在体和离体实验证实,凋亡及凋亡过程中的相关基因表达变化与浅低温的保护作用密切相关。就低温对线粒体介导的细胞凋亡效应作一综述。     

Effects of hypothermia on myocardial substrate selection

BACKGROUND: Hypothermia lowers the metabolic rate and increases ischemic tolerance but the effects of temperature on myocardial substrate selection are not well defined. METHODS: Isolated rat hearts were perfused with physiologic concentrations of 13C labeled lactate, pyruvate, acetoacetate, mixed long-chain fatty acids, and glucose. Hearts were cooled over 5 to 10 minutes to one of four target temperatures (37 degrees, 32 degrees, 27 degrees, or 17 degrees C), then perfused for an additional 30 minutes, freeze-clamped, and extracted. 13C NMR spectra were obtained and substrate oxidation patterns were determined by isotopomer analysis. RESULTS: Although hearts in all groups were supplied with identical substrates, the percentage of acetyl-CoA oxidized within the citric acid cycle that arose from fatty acids decreased significantly from 53.8% +/- 0.8% in the 37 degrees C group to 33.1% +/- 3.3% in the 17 degrees C group. Lactate or pyruvate utilization increased from 3.3% +/- 0.5% to 25.7% +/- 3.6%, respectively (p < 0.05 by one-way ANOVA). CONCLUSIONS: These data suggest that moderate hypothermia suppresses fatty acid oxidation and deep hypothermia significantly increases utilization of lactate and pyruvate. These effects may result from relative inhibition of catabolism of complex molecules such as fatty acids, or stimulation of pyruvate dehydrogenase. These effects on substrate metabolism may play a role in myocardial protection afforded by hypothermia.     

Long-term outcome following testicular ischemia in the rat

Male germ cells are quite sensitive to interruption in blood flow. Eight weeks after subjection to 45 minutes of testicular ischemia, the spermatogenic epithelium of the rat remains significantly damaged, though other cell types are well preserved. The authors evaluated the testicular recovery of the rats at 8 and 72 weeks after the 45-minute period of warm ischemia. Twenty-eight rats were studied: 14 underwent 45 minutes of total left testicular ischemia; 14 received no treatment. Four rats from each group were necropsied at 8 weeks to document the ischemic injury. At 72 weeks, the 18 surviving rats were necropsied to evaluate the long-term outcome of the treatment. At 8 weeks, significant left testicular injury was documented. However, at 72 weeks there was no difference in testicular weight or sperm head count between the groups: in all 36 testicles, the repopulation index was 1.00, the epididymal index was 3+, the modified Johnsen index was 14, and the spermatic cord score was 7 (all are maximum obtainable scores). Neither contralateral orchiopathy nor injury to spermatic cord structures was observed. Our work shows that ischemia-induced testicular injury is fully reversible with time in this model.     

浅低温抑制脑缺血神经元凋亡的机制

浅低温是一近年来研究较多且疗效较为肯定治疗脑缺血的措施,但其确切作用的分子机制尚未阐明。凋亡参与缺血性脑损伤,且加重损伤程度。近年研究发现浅低温可多途径多靶点抑制缺血诱导的神经元凋亡,减少神经元延迟性死亡(PND)而产生脑保护作用。现就浅低温抑制脑缺血神经元凋亡机制的研究作一综述     

脑缺血浅低温治疗时间窗的研究进展

背景 动物实验和临床研究证实浅低温(32℃～34℃)对脑缺血神经元有显著的保护作用.但是,何时开始浅低温,以及浅低温需要维持多长时间(即浅低温治疗时间窗)才能起到最大限度的神经保护作用,尚无明确定论.目的 综述脑缺血浅低温治疗时间窗的研究进展情况.内容 阐述治疗时间窗概念及脑缺血浅低温治疗时间窗的研究进展;讨论早期浅低温和晚期浅低温脑保护的可能作用机制.趋向 阐明浅低温治疗时间窗及机制,更好地应用浅低温于临床脑保护.