Role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury / 中国药理学通报

Aim To investigate the role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury and related mechanism. Methods SD rats were randomly divided into five groups: Sham operation group(Sham), model group(IR), remote preconditioning of trauma group(RPCT), TRPA1 inhibitor+remote preconditioning of trauma group(TCS+RPCT)and TRPA1 inhibitor group(TCS). The model of myocardial ischemia/reperfusion in rats was established, and the hemodynamics was monitored throughout the process. After reperfusion, the rat heart was taken to measure the myocardial infarction area and myocardial apoptosis rate, the activity and protein expression of mitochondrial aldehyde dehydrogenase 2(ALDH2)and the expression of 4-hydroxynonenal(4-HNE)were detected. Results Compared with sham group, myocardial infarction area and myocardial apoptosis cell increased. Meanwhile, the activity and expression of ALDH2 decreased and the production of 4-HNE increased in IR group. However, compared with IR group, RPCT group had decreased myocardial infarction area and the rate of cardiomyocyte apoptosis, the activity and expression of ALDH2 increased, the production of 4-HNE decreased. And then, compared with RPCT group, TCS+RPCT group reduced the myocardial protective effect of remote preconditioning of trauma. Conclusions TRPA1 receptor mediates the effect of remote preconditioning of trauma alleviating myocardial ischemia/reperfusion injury in rats. Its mechanism may be related to regulating ALDH2 activity and protein expression, and affecting the content of 4-HNE.

Exploring the role of neurogenic pathway-linked cholecystokinin release in remote preconditioning-induced cardioprotection

Abstract Purpose: The current study explored the involvement of neurogenic pathway-linked cholecystokinin (CCK) release in RIP-induced cardioprotection in rats. Methods: Male Wistar rats were subjected to four cycles of alternate episodes of ischemia and reperfusion (five min each) to induce RIP. Thereafter, the hearts were subjected to global ischemia and reperfusion ex vivo. The myocardial damage was assessed by quantifying the levels of heartspecific biochemicals i.e. LDH-1, CK-MB and cTnT. Apoptotic cell injury was assessed by measuring the levels of caspase-3 and Bcl-2. The levels of CCK were measured in the plasma following RIP. Results: Exposure to RIP significantly increased the plasma levels of CCK and attenuated IR-induced myocardial injury. Administration of CCK antagonist, proglumide significantly attenuated RIP-induced cardioprotection. Administration of hexamethonium, a ganglion blocker, abolished RIP-induced increase in plasma CCK levels and cardioprotective effects. Exogenous delivery of CCK-8 restored the effects of RIP in hexamethonium treated animals. Conclusion: RIP activates the neurogenic pathway that may increase the plasma levels of CCK, which may act on the heart-localized CCK receptors to produce cardioprotection against I/R injury.

Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

Effects of intrathecal morphine remote preconditioning on Akt/eNOS signaling pathways and myocardial apoptosis in rats / 中华急诊医学杂志

Objective To investigate the effects of intrathecal morphine remote preconditioning (MRPC) on protein-serine-threonine kinases-endothelial nitric oxide synthase (Akt/eNOS) signaling pathways and cardiac myocyte apoptosis in rats.Methods Male SD rats weighing 280-320 g were used in this study.A needle was inserted through a surgically created hole into the sub-dural space of spinal cord.Thirty-six rats in which intrathecal needle was successfully placed without complication were randomly divided into 3 groups (n =12 in each).In group Ⅰ sham operation was performed (Sham).In group Ⅱ myocardial I/R was produced (I/R).In group Ⅲ morphine was given intrathecally in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MRPC).Myocardial I/R was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion.The animals were then sacrificed and hearts removed for measurement of area at risk (AAR) and infarct size area (IS).IS/AAR ratio was calculated.Myocardial apoptosis was detected by TUNEL and apoptotic index (the number of apoptotic myocardial cells/the total number of myocardial cells) was calculated.The levels of Akt,phosphorylated Akt (p-Akt) and eNOS was determined by Western blot.Results The infarct size,myocardial cell apoptotic index and pAkt level were higher and eNOS level was significantly lower in I/R group than those in group Sham (P ＜ 0.01).MRPC significantly reduced the infarct size and myocardial cell apoptotic index,and pAkt and eNOS level up-regulated in group RMPC compared with group I/R (P ＜ 0.01).Conclusions Akt/eNOS signaling pathways probably participate in the protective effects of intrathecal morphine remote preconditioning against myocardial I/R injury and myocardial cell apoptosis in rats.

Mechanisms and Prospects of Ischemic Tolerance Induced by Cerebral Preconditioning / 대한배뇨장애요실금학회지

In the brain, brief episodes of ischemia induce tolerance against a subsequent severe episode of ischemia. This phenomenon of endogenous neuroprotection is known as preconditioning-induced ischemic tolerance. The purpose of this review is to summarize the current state of knowledge about mechanisms and potential applications of cerebral preconditioning and ischemic tolerance. Articles related to the terms ischemic preconditioning and ischemic tolerance were systematically searched via MEDLINE/PubMed, and articles published in English related to the nervous system were selected and analyzed. The past two decades have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. Although both rapid and delayed types of tolerance have been documented in experimental settings, the delayed type has been found to be more prominent in the case of neuronal ischemic tolerance. Many intracellular signaling pathways have been implicated regarding ischemic preconditioning. Most of these are associated with membrane receptors, kinase cascades, and transcription factors. Moreover, ischemic tolerance can be induced by exposing animals or cells to diverse types of endogenous and exogenous stimuli that are not necessarily hypoxic or ischemic in nature. These cross-tolerances raise the hope that, in the future, it will be possible to pharmacologically activate or mimic ischemic tolerance in the human brain. Another promising approach is remote preconditioning in which preconditioning of one organ or system leads to the protection of a different (remote) organ that is difficult to target, such as the brain. The preconditioning strategy and related interventions can confer neuroprotection in experimental ischemia, and, thus, have promise for practical applications in cases of vascular neurosurgery and endo-vascular therapy.

Effects of remote preconditioning on inflammatory cytokines and respiratory index of rabbit lung injured by ischemia-reperfusion / 解放军医学杂志

Objective To investigate the effects of remote preconditioning on inflammatory cytokines and respiratory index of rabbit lung injured by ischemia/reperfusion.Methods Eighteen rabbits were randomly divided into three groups(6 each):control group(C),ischemia-reperfusion group(I/R)and remote preconditioning group(R).The plasma concentrations of interleukin-6(IL-6),tumor necrosis factor-?(TNF-?)and interleukin-10(IL-10)were measured before ischemia and 60,120 and 180 min after reperfusion.Respiratory index(A-aO2/PaO2)was calculated before ischemia and 15,30,60,120 and 180 min after reperfusion.The animals were sacrificed after reperfusion,and the left lung was removed for calculation of wet/dry(W/D)ratio and lung permeability index,histological examination was done with light microscope,and diffuse alveolar damage(DAD)scores was estimated.Results The plasma concentrations of IL-6 and TNF-? were significantly higher in I/R group than in C group(P