缺血再灌注对老年心脏的损伤机制及研究进展

随着老年人的数量以及心血管疾病发病率的不断增加,明确老年人手术期间心肌缺血再灌注加重对心脏的损伤及其保护机制就显得尤为重要。尽管早期的预缺血再灌注是目前最流行的预防心脏损伤的方法,然而这只能部分减缓对心脏的损伤,而且研究发现对老年心脏作用不明显。目前的研究表明,老年心脏对缺血再灌注损伤更为敏感,造成损伤加重。为了开发新的保护心脏的方法,要深入理解老年心脏与正常心脏在结构和功能上的差异,以及这些差异对缺血再灌注损伤的影响。本综述重点讨论老年心脏与年轻心脏细胞和组织间的差异,以及这些差异诱导老年心肌在缺血再灌注中损伤加重的机制。

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

Liver ischaemic preconditioning （IPC） is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury （IRI）, which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords ＂liver＂, ＂ischaemic reperfusion＇, ＂ischaemic preconditioning＂, ＂regeneration＂, ＂hepatectomy＂ and ＂transplantation＂. The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.

Protective effect of L-arginine preconditioning on ischemia and reperfusion injury associated with rat small bowel transplantation

AIM: To investigate the protective effect and possible mechanism of L-arginine preconditioning on ischemia and reperfusion injury associated with small bowel transplantation (SBT).METHODS: Male inbred Wistar rats weighting between 180 and 250 g were used as donors and recipients in thestudy. Heterotopic rat SBT was performed according to the techniques of Li and Wu. During the experiment, intestinal grafts were preserved in 4 ℃ Ringer's solution for 8 h before being transplanted. Animals were divided into three groups. In group 1, donors received intravenous L-arginine (50 mg/kg, 1 mL) injection 90 min before graft harvesting. However, donors in control group were given normal saline (NS) instead. In group 3, six rats were used as sham-operated control. Specimens were taken from intestinal grafts 15 min after reperfusion. Histological grading, tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were assessed. The graft survival of each group was monitored daily until 14 d after transplantation. RESULTS: Levels of MDA and MPO in intestine of shamoperated rats were 2.0±0.22 mmol/g and 0.66±0.105 U/g. Eight hours of cold preservation followed by 15 min of reperfusion resulted in significant increases in tissue MDA and MPO levels. Pretreatment with L-arginine before graft harvesting resulted in lower enhancement of tissue levels of MDA and MPO and the differences were significant (4.71±1.02 mmol/g vs8.02±3.49 mmol/g, 1.03±0.095 U/g vs 1.53±0.068 U/g, P＜0.05). Besides, animals in L-arginine pretreated group had better histological structures and higher 2-wk graft survival rates comparing with that in NS treated group (3.3±0.52 vs6±0.1, 0/6 vs6/6, P＜0.05or 0.01).CONCLUSION: L-arginine preconditioning attenuates ischemia and reperfusion injury in the rat SBT model,which was due to antioxidant activities partially.

Protective effect of ischemic preconditioning on liver

Objective:: To study the protective effect of ischemic preconditioning (IPC) on the hepatic ischemia-reperfusion injury. Methods: The model of rat liver subjected to ischemia/reperfusion (I/R) injury was made. All 24 mice were divided randomly into 3 groups and anesthetized by 2% sodium pentobarbital (30-40 mg/kg). The enzyme activity of AST, ALT, LDH, SOD and the content of LPO were assayed respectively. Specimens were observed under transmission electron microscope. Results: IPC prevented the increase of ALT, AST and LDH in the blood and that of LPO in the tissues (P< 0.05 ), and maintained high level of SOD in the tissues (P< 0.05 ). Conclusions: IPC has protective effect on the liver function.

Protective effect of electroacupuncture preconditioning at zúsānlǐ(足三里 ST36) on mitochondria in the intestinal ischemia/reperfusion injury

Objective： The study explored the effect of applying electroacupuncture（EA） preconditioning at ST 36 on mitochondria in rats with intestinal ischemia/reperfusion injury.Methods： Forty SD rats were divided into four sets： sham operation group（sham group）; intestinal ischemia/reperfusion group（I/R group）; EA preconditioning at ST 36 followed by intestinal ischemia/reperfusion injury（ST 36 ＋ I/R group）; EA preconditioning at the lateral site away from ST360.5 cm followed by intestinal ischemia/reperfusion injury（N＋I/R group）. For the sham group, the rats were opened abdominal cavity for 3 h and 20 min and their abdominal cavities were covered with wet gauze avoiding drying and kept on the thermostat at 37 0 C. For the ischemia/reperfusion（I/R） group,rats were anaesthetised and their abdominal cavities were opened to expose jejunum segments. The segment＇s collateral blood supply was restricted by bilateral ligation of the intestine. Next, one of the branches of a mesenteric artery was occluded with a thread for 20 min and then the thread was released after such ischemia conditions, keeping reperfusion for 3 h. For the ST36 ＋ I/R group, the electroacupuncture at ST36 was first performed, then the intestinal ischemia/reperfusion model was constructed. For the N ＋ I/R group, electroacupuncture at non ST36 acupoint, which is away from ST36 about 0.5 cm, and then the intestinal ischemia/reperfusion model was performed. Measurements of the levels of inflammatory markers tumour necrosis factor a（TNFa） and interleukin-1 beta（IL-1β）, cytochrome c（CYCS）, and the mitochondrial membrane pro-apoptotic protein（BAX）, anti-apoptotic protein Bcl-2 were performed.Results： Compared to I/R group, the intensity of cytoplasmic CYCS in intestinal tissues was significantly decreased in the ST 36 ＋ I/R group（1.65 vs. 0.18, p〈0.05）. Compared to N ＋ I/R group, the intensity of cytoplasmic CYCS in intestinal tissues was also dramatically declined in the ST 36 ＋ I/R group（1.37 vs. 0.18, p〈0.05）. The level of CYCS in mitochondria in rats in the ST 36 ＋ I/R group were appreciably increased than those of rats in the I/Rgroup（1.42 vs. 0.06, p〈0.05）, and CYCS in mitochondria was also largely expressed in ST36 ＋ I/R group than N ＋ I/R group（1.42 vs. 0.08, p〈0.05）. Bcl-2 was shown to be elevated in the ST 36 ＋ I/R group than I/R group（1.01 vs. 0.10） and N ＋ I/R group（1.01 vs. 0.09, all p〈0.05）, whereas BAX expression was greatly decreased in the ST36 ＋ I/R group than I/R group（0.11 vs.0.78） and N ＋ I/R group（0.11 vs. 0.87, all p〈0.05）.Conclusion： The results suggest the EA intervention has a protective effect upon mitochondria, preventing CYCS release and the subsequent activation of downstream apoptosis pathway. It is proposed that patients due to undergo gastrointestinal surgery get benefit from EA preconditioning at ST 36.