Tricarboxylic acid cycle metabolites: new players in macrophage.

Metabolic remodeling is a key feature of macrophage activation and polarization. Recent studies have demonstrated the role of tricarboxylic acid (TCA) cycle metabolites in the innate immune system. In the current review, we summarize recent advances in the metabolic reprogramming of the TCA cycle during macrophage activation and polarization and address the effects of these metabolites in modulating macrophage function. Deciphering the crosstalk between the TCA cycle and the immune response might provide novel potential targets for the intervention of immune reactions and favor the development of new strategies for the treatment of infection, inflammation, and cancer.

[Effect of electroacupuncture preconditioning on neuronal activities in lateral hypothalamus area of myocardial ischemia reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning of "Shenmen" (HT7)-"Tongli" (HT5) segment of the Heart Meridian on neuronal electrical activities of lateral hypothalamus area (LHA) in rats with myocardial ischemia reperfusion injury (MIRI), so as to investigate its possible mechanism underlying improvement of MIRI. METHODS: Twenty-four SD rats were randomly divided into sham, model, EA and damage + EA (D+EA) groups, with 6 rats in each group. The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 2 h. In the sham operation group, the ADB was only threaded beneath the artery without ligation. EA (2 Hz, 1 V) was applied to bilateral HT7-HT5 for 20 min, once daily for 7 days. In the D+EA group, FN was injected with 0.4 µL of 1 g/L kainic acid solution. Electrocardiogram (ECG) of the neck-thoracic lead was recorded by using PowerLab. The electrical activities of the LHA region were recorded by the implanted microelectrode array (2×4) and Plexon multi-channel acquisition system. Cluster analysis of neuronal signals was carried out by Offline Sorter software. The discharge waveforms, autocorrelation and cross-correlation of neuronal activities were analyzed by using Neuro Explorer software. RESULTS: Compared with the sham group, the ECG-ST height was significantly increased (P<0.05), the discharge frequency of pyramidal neurons was significantly reduced (P<0.01), while the discharge frequency of interneurons was increased (P<0.01) in the model group. After EA treatment, the ECG-ST height was significantly decreased (P<0.05), the discharge frequency of pyramidal neurons was significantly increased (P<0.01) relevant to the model group. In comparison with the EA group, the ECG-ST height in the D+EA group was significantly elevated (P<0.05), whereas the discharge frequency of pyramidal neurons was significantly decreased (P<0.01). The discharge frequency of interneurons was kept increasing after MIRI. Real-time spectrum analysis showed that the local field potential spectrum energy of the EA group was significantly lower than that of the model group and the D+EA group. CONCLUSION: EA preconditioning of Heart Meridian can significantly increase the discharge frequency of LHA excitatory pyramidal neurons and reduce the energy of the local field potential spectrum, which maybe one of the important mechanisms of EA in anti -MIRI.

[Effect of electroacupuncture preconditioning on the contents of dopamine and 5-hydroxytryptamine in lateral hypothalamus area and cerebellar fastigial nucleus of rats with myocardial ischemia-reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI. METHODS: Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group. RESULTS: In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (P<0.01), those in the EA heart meridian group, the LHA plus heart meridian group, the FN plus heart meridian group and the EA lung meridian group were lower than those in the model group successively (P<0.01) and those in the EA heart meridian group were lower than those in the EA lung meridian group, the LHA plus heart meridian group and the FN plus heart meridian group successively (P<0.01). The contents of DA and 5-HT in FN and LHA in the model group were lower than those in the sham-operation group (P<0.01). Except in the groups with nucleus lesions, the contents of DA and 5-HT in FN and LHA of each intervention group were higher than those in the model group (P<0.01), the contents of DA and 5-HT in FN in the EA heart meridian group were higher than those in the EA lung meridian group and the LHA plus heart meridian group (P<0.01) and the content of 5-HT in LHA was higher than those in the EA lung meridian group and the FN plus heart meridian group (P<0.01) separately, the content of DA in LHA was higher than that in the EA lung meridian group (P<0.01). CONCLUSION: EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.

Mechanisms of Electroacupuncture Pretreatment in Alleviating Myocardial Ischemia Reperfusion Injury: Interactions between the Cerebellar Fastigial Nucleus and Lateral Hypothalamic Area.

Background: Myocardial ischemia reperfusion injury (MIRI) is an important mechanism of post-myocardial infarction injury and a main cause of death in patients with ischemic heart disease. Electroacupuncture (EA) pretreatment is effective for the prevention and treatment of MIRI, but mechanisms mediating the effects of cardiovascular disease EA treatments remain unclear. Objectives: To determine whether the lateral hypothalamus (LHA) and the cerebellar fastigial nucleus (FN) are involved in the protective effects of EA stimulation on MIRI. Methods: EA pretreatment was performed for 7 days before the establishment of the MIRI model. ST-segment changes on electrocardiograms were recorded and the Curtis-Walker arrhythmia score was used to evaluate changes in reperfusion injury. Hematoxylin-eosin staining was applied to evaluate the pathological and morphological changes in myocardial tissue. c-fos expression in the LHA and FN was determined by immunofluorescence staining. Glutamic (Glu) and γ-Aminobutyric acid (GABA) levels were measured using a high-performance liquid chromatography-electrochemical method. Results: EA pretreatment reduced ST-segment elevation, arrhythmia scores, and morphological changes in MIRI myocardial cells in rats, and decreased the c-fos protein expression in LHA/FN nuclei. MIRI was associated with an imbalance between GABA and Glu levels, whereas EA pretreatment increased GABA levels and decreased Glu levels in the LHA/FN. Conclusion: FN and LHA are involved in the EA-mediated attenuation of MIRI. Pretreatment with EA plays a protective role in the myocardium by regulating Glu and GABA release in the LHA and FN.

[Effect of different concentrations of moxa smoke exposure on nasal mucosal injury and expression of serum IL-1, IL-6 and TNF-α in rats].

OBJECTIVE: To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion. METHODS: Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method. RESULTS: In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group (P<0.01). The hierarchical structure of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was unclear, disordered, necrotic and inflammatory cell infiltration was serious; the number of apoptotic cells in olfactory epithelium of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was more than that in the normal control group and the low-concentration moxa smoke group (P<0.01), that in the high-concentration moxa smoke group was more than the moderate-concentration group (P<0.01). The serum levels of IL-1, IL-6 and TNF-α in the low-concentration moxa smoke group, the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the normal control group (P<0.01), and those in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the low-concentration moxa smoke group (P<0.01), and those in the high-concentration moxa smoke group were higher than moderate-concentration moxa smoke group (P<0.01). CONCLUSION: The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.