三七总皂苷脂质体的生理适应性及其对心脑血管的保护作用

目的：研究三七总皂苷(PNs)脂质体的生理适应性及其对心脑血管的保护作用。方法：采用蟾蜍上腭纤毛运动持续时间、大鼠肺水肿指数以及肺组织病理改变作为指标，考察PNS脂质体的生理适应性；通过结扎大鼠冠状动脉建立急性心肌梗死模型以及夹闭蒙古沙土鼠双侧颈总动脉建立脑缺血一再灌注模型，观察PNS脂质体对心脑血管疾病的作用。结果：PNS脂质体组蟾蜍黏膜纤毛运动持续时间是对照组的92．14％，大鼠的肺水肿指数和肺组织病理改变与PNS溶液组相比有显著差异，接近对照组。PNS脂质体在降低大鼠心肌梗死范围和缓解沙土鼠脑缺血一再灌注过程中出现的卒中指数时呈剂量依赖性，大剂量效果更优。结论：PNS脂质体具有良好的生理适应性，对实验性心肌梗死和脑缺血一再灌注均有较好的保护作用。     

雷公藤内酯醇对大鼠脑局灶性缺血再灌注后脑神经细胞凋亡的影响

目的 :探讨雷公藤内酯醇 (triptolide,TL)对局灶性脑缺血再灌注大鼠脑组织内神经细胞凋亡的影响。方法 :采用线栓法制备大鼠局灶性脑缺血再灌注模型。观察雷公藤内酯醇 (0.2～0.4mg·kg^-1,ip)对各组大鼠神经功能缺失评分的影响 ,应用免疫组化染色技术 ,观察大鼠大脑中动脉闭塞侧髓过氧化物酶 (MPO)免疫染色阳性细胞数、细胞原位凋亡 (TUNEL)染色阳性细胞数的变化。结果 :与损伤模型组比较 ,雷公藤内酯醇两治疗组可明显改善大鼠神经功能的受损程度 ,并减少MPO及TUNEL染色阳性细胞数。结论 :雷公藤内酯醇具有抑制局灶性脑缺血再灌注时白细胞浸润、抗神经细胞凋亡作用 ,从而改善受损的神经功能。     

Diazoxide may protect endothelial glycocalyx integrity during coronary artery bypass grafting

Abstract

Objectives. Plasma hyaluronan and syndecan-1 levels represent shedding of the endothelium glycocalyx during ischemia and edema. Diazoxide, a K_ATP-channel opener, has been shown to decrease myocardial edema during coronary artery bypass grafting (CABG). We evaluated whether Diazoxide exerts an impact on plasma hyaluronan and syndecan-1 levels during CABG. Design. Representative blood samples for hyaluronan and syndecan-1, before, during and after surgery, were obtained in 13 out of 16 patients that had a history of stable coronary artery disease undergoing CABG with or without Diazoxide. Electron microscopy from biopsies procured from the right atrium in 9 patients was performed to confirm ultrastructural differences among patients before and during CABG. Results. Ultrastructural differences were apparent between individual patients already before operation at base line reflecting differences in the severity of myocardial ischemia and edema. A significant decrease of hyaluronan and syndecan-1 values was observed in patients with Diazoxide after surgery (p < 0.04). Significant correlation of Plasma hyaluronan and syndecan-1 levels was observed in patients with Diazoxide but not in controls (p < 0.005, Spearman rank rho). Conclusion. Diazoxide may have an impact on levels of peripheral plasma hyaluronan and syndecan-1 after CABG, suggesting decreased shedding of the endothelial glycocalyx layer.     

Ginsenoside Rb3 ameliorates myocardial ischemia-reperfusion injury in rats

Context: Panax ginseng C. A. Mey (Araliaceae) has been widely used in clinic for treatment of cardiovascular diseases in China. Ginsenoside Rb3 is the main chemical component of Panax ginseng.

Objective: The aim of this study was to evaluate the effect of ginsenoside Rb3 on myocardial ischemia-reperfusion injury in rats.

Methods: Sprague–Dawley rats were orally treated with Rb3 (5, 10 or 20?mg/kg) daily for 3 days followed by subjecting to left anterior descending coronary artery ligation for 30?min and reperfusion for 24?h.

Results: This study showed that ginsenoside Rb3 treatment resulted in a reduction in myocardial infarct size. Ginsenoside Rb3 significantly attenuated the changes of creatine kinase activity and lactate dehydrogenase activity. The cardioprotective effect of ginsenoside Rb3 was further confirmed by histopathological examination. Ginsenoside Rb3 alleviated the increase of malondialdehyde content and the decrease of superoxide dismutase activity in left ventricle. Treatment with ginsenoside Rb3 also decreased plasma endothelin and angiotensin II levels.

Conclusion: These findings suggested that ginsenoside Rb3 possesses the effect against myocardial IR injury and the underlying mechanism is related to its antioxidant activity and microcirculatory improvement.     

Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

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Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b⁺ cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b⁺/Ly6C^high population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b⁺/Ly6C^intermediate population peaked during kidney repair. The CD11b⁺/Ly6C^low population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b⁺/Ly6C^intermediate population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b⁺/Ly6C^low population had a profibrotic phenotype. All populations, including the CD11b⁺/Ly6C^high population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b⁺/Ly6C^intermediate and CD11b⁺/Ly6C^low populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b⁺/Ly6C⁺ monocyte/macrophage populations in the pathophysiology of disease after AKI.     

Protective role of melatonin given either before ischemia or prior to reperfusion on intestinal ischemia-reperfusion damage

Tissue injury resulting from ischemia-reperfusion is of fundamental importance. Experimental evidence suggests that the generation of reactive oxygen species is significantly responsible for this type of injury. In the present study, besides investigating the protective role of melatonin on tissue damage caused by intestinal ischemia-reperfusion, the protective activity of this compound was also analyzed in both pre- and post ischemia melatonin-treated rats. The activities of the main antioxidative enzymes, catalase, superoxide dismutase and glutathione peroxidase in the intestine showed significant (P < 0.05) increases in melatonin-treated animals that were subjected to ischemia/reperfusion compared with those subjected only to ischemia/reperfusion. Also, results clearly indicate that the level of malondialdeyhde, an index of lipid peroxidation, decreased significantly (P < 0.05) when rats subjected to intestinal/reperfusion were given melatonin either before ischemia or before reperfusion.     

GRP78与 CHOP在缺血再灌注损伤中的作用

缺血再灌注（ischemia-reperfusion ,IR）过程中多种因素可导致内质网应激（endoplasmic reticulum stress response,ERS）, ERS参与缺血再灌注（ ischemia-reperfusion injury,IRI）的发展过程。总结ERS抗凋亡标志物GRP78与促凋亡标志物CHOP在IRI中的作用。 IRI时GRP78与CHOP表达的变化及其作用。明晰GRP78与CHOP参与IRI的机制。     

谷氨酰胺对大鼠肠缺血再灌注损伤后闭合蛋白的保护作用

目的:探讨谷氨酰胺(Gln)对大鼠肠缺血再灌注损伤后闭合蛋白(occludin)的保护作用及其可能机制。方法:成年雄性Wistar大鼠30只随机分为假手术组(sham组)、缺血再灌注损伤组(I/R组)和谷氨酰胺预处理组(Gln组)。Gln组给予谷氨酰胺1 g·kg-1·d-1连续灌胃7 d。Sham组和I/R组以同等剂量生理盐水灌胃7d。Sham组仅分离肠系膜上动脉而根部不夹闭。I/R组和Gln组均用无损伤血管夹夹闭SMA根部30 min后放松血管夹形成再灌注损伤模型。各组大鼠均于制模后24 h采集静脉血和回肠标本。酶联免疫吸附试验检测血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10和IL-2水平。全自动生化仪检测超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)水平。免疫组化及Western blotting法检测occludin蛋白的表达情况。结果:I/R组occludin蛋白表达明显低于正常对照组及谷氨酰胺处理组(P0.05);I/R组TNF-α和MDA水平均高于sham组和Gln组(P0.05)。I/R组血清的SOD活力、GSH、GSH-Px、IL-10和IL-2均低于sham组和Gln组(P0.05)。结论:谷氨酰胺对肠缺血再灌注损伤后的occludin蛋白具有保护作用,其机制可能与抑制炎症反应、抗氧化应激有关。     

Vitamin E attenuates myocardial ischemia-reperfusion injury in murine AIDS

The incidence of myocardial infarction in patients who have the aquired immunodeficiency syndrome (AIDS) is increasing. However, no effective therapeutic agents have been discovered to reduce myocardial ischemia-reperfusion (I/R) injury in pathologies associated with AIDS. The aim of this study was to determine if infarct size is increased in murine AIDS after I/R injury and if I/R injury could be attenuated with vitamin E supplementation. Three groups of mice were studied: control, murine AIDS, and murine AIDS with vitamin E supplementation. Anesthetized mice were subjected to 30 min of left anterior descending coronary artery occlusion and 120 min of reperfusion. The hearts in mice that had murine AIDS had a larger infarct size compared to controls after I/R injury. Vitamin E supplementation significantly reduced infarct size and inhibited polymorphonuclear neutrophil (PMN) CD11b expression (p<0.05). However, vitamin E supplementation did not affect PMN reactive oxygen species (ROS) production and platelet CD62p expression. These results suggest that the reduction of myocardial I/R injury with vitamin E supplementation may be the result of the inhibition of PMN CD11b expression. Vitamin E may be a promising prophylactic agent for the reduction of the severity of myocardial I/R injury in patients who have AIDS.