ABSTRACT
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.
ABSTRACT
Objective@#To explore the expressions of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in the dorsal root ganglion (DRG) and their action mechanisms in the rat model of orchialgia.@*METHODS@#The models of orchialgia were established in male SD rats by injection of 2% acetic acid into the testis. Then the number of spontaneous pain responses and withdrawal latency in the model rats were recorded by behavioral tests and the expressions of TRPV1 and TRPA1 in T13－L1 DRGs determined by RT-qPCR, Western blot and immunofluorescence staining.@*RESULTS@#Compared with the normal control rats, the orchialgia models showed a significant increase in the number of spontaneous pain responses (0.13 ± 0.35 vs 22.63 ± 3.42, P<0.01) and a decrease in the withdrawal latency at 4 hours after injection (［12.75 ± 1.50］ vs ［4.85 ± 1.00］ s, P<0.05). The mRNA expressions of both TRPV1 and TRPA1 were observed in the membrane of the neurons in the DRG, the former increased by 1.77 times and the latter by 1.75 times that of the control (P<0.05).@*CONCLUSIONS@#The expressions of TRPV1 and TRPA1 were up-regulated in the DRG of the rat models of orchialgia, which may be involved in the allodynia and hyperalgesia of the rats.
Subject(s)
Animals , Male , Rats , Acetic Acid , Ganglia, Spinal , Metabolism , Hyperalgesia , Metabolism , Membrane Glycoproteins , Oxidoreductases , Rats, Sprague-Dawley , TRPA1 Cation Channel , Metabolism , TRPV Cation Channels , Metabolism , Testicular Diseases , Metabolism , Up-RegulationABSTRACT
Transient receptor potential ankyrin 1 (TRPA1) is a family member of the transient receptor potential (TRPs). It is primarily localized to a subpopulation of primary sensory neurons, such as trigeminus, vagus and dorsal root ganglia. Neuropathic pain is often caused by peripheral nerve injury, diabetes and chemotherapeutics. A large of oxidative/nitrative stress products are produced during neuropathic pain, which cause acute nociception, allodynia, and hyperalgesia. TRPA1 antagonists may be beneficial in the treatment of neuropathic pain. Here, the role of TRPA1 in neuropathic pain is summarized.
ABSTRACT
Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfona (FAST DiI). Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST DiI-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST DiI-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.