Electroacupuncture attenuates myocardial ischemia-reperfusion injury by inhibiting microglial engulfment of dendritic spines.

A major side effect of reperfusion therapy following myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture preconditioning (EA-pre) has a long history in the treatment of cardiovascular diseases. Here, we demonstrate how EA-pre attenuates MIRI by affecting the phagocytosis of neuronal dendritic spines of microglia of the fastigial nucleus (FNmicroglia). We observed that EA-pre increased activity in FNGABA and then improved myocardial injury by inhibiting abnormal activities of glutaminergic neurons of the FN (FNGlu) during MIRI. Interestingly, we observed changes in the quantity and shape of FN microglia in mice treated with EA-pre and a decrease in the phagocytosis of FNGABA neuronal dendritic spines by microglia. Furthermore, the effects of improving MIRI were reversed when EA-pre mice were chemically activated by intra-FN lipopolysaccharide injection. Overall, our results provide new insight indicating that EA-pre regulates microglial engulfment capacity, thus promoting the improvement of cardiac sympathetic nervous disorder during MIRI.

[Effect of moxibustion on TLR4/MyD88/NF-κB signaling pathway in colon of diarrhea-predo-minant irritable bowel syndrome rats].

OBJECTIVE: To observe the effect of moxibustion on serum inflammatory factors, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor Kappa B (NF-κB) in colon tissue of rats with diarrhea-predominant irritable bowel syndrome (IBS-D)，so as to explore the mechanism of moxibustion in the treatment of IBS-D. METHODS: Healthy male SD rats were randomly divided into blank group, model group and moxibustion group, with 8 rats in each group. The IBS-D model was established by chronic restraint combined with gavage of Senna-leaf solution. The rats of the moxibustion group was treated with moxibustion at "Tianshu"(ST25)and "Shangjuxu"(ST37)for 30 min， once a day for 7 d. After the intervention, the rate of loose stools and the minimum threshold volume of abdominal withdrawal reflex (AWR) induced by colorectal distension were observed. The contents of serum inflammatory factors IL-1ß, TNF-α and IL-6 were detected by ELISA. The pathological changes of rat colon were observed by H.E. staining. The average optical density of TLR4 and NF-κB (p65) in colon tissue was detected by immunohistochemistry. The relative expressions of TLR4, MyD88 and NF-κB (p65) mRNAs in colon tissues were detected by real-time fluorescence quantitative PCR, and the expression levels of TLR4, MyD88 and NF-κB (p65) proteins in colon tissues were detected by Western blot. RESULTS: There was a mild degree of inflammation in colon in rats of the model group. Compared with the blank group, the minimum volume threshold of AWR decreased significantly (P< 0.01), and the rate of loose stools, the contents of IL-1ß, IL-6 and TNF-α in serum as well as the expressions of TLR4, MyD88, NF-κB (p65) mRNAs and protein in colon tissues were significantly increased in the model group (P<0.01). Compared with the model group, the inflammation was alleviated in colonic mucosa, the minimum volume threshold of AWR increased significantly (P<0.01), and rate of loose stools decreased significantly (P<0.01) in the moxibustion group, the contents of IL-1ß, TNF-α and IL-6 in serum and the expression levels of TLR4, MyD88, NF-κB (p65) mRNAs and proteins in colon tissue decreased significantly in the moxibustion group (P<0.01). CONCLUSION: Moxibustion ST25 and ST37 can improve diarrhea symptom and visceral hypersensitivity in IBS-D rats, which may be related with its effects in inhibiting TLR4/MyD88/NF-κB signaling pathway and reducing the expression of inflammatory factors.

[Moxibustion relieves abdominal hypersensitivity and diarrhea by regulating colonic 5-hydroxytryptamine signaling pathway in rats with diarrhea type irritable bowel syndrome].

OBJECTIVE: To observe the effect of moxibustion on visceral pain, diarrhea, colonic 5-hydroxytryptamine (5-HT) content, and expression of tryptophan hydroxylase 1 (TPH1), serotonin reup take transporter (SERT) and 5-hydroxytryptamine receptor 3 (5-HT3R) in colon tissue of rats with diarrhea irritable bowel syndrome (IBS-D), so as to reveal its underlying mechanisms in treating IBS-D. METHODS: Thirty male SD rats were randomly divided into blank control, model and moxibustion groups (n＝10 rats in each group). The IBS-D model was established by chronic restraint combined with gavage of Senna leaf solution. Moxibustion was applied to bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37) for 30 min, once a day for 7 days. After the treatment, the loose stool rate (number of loose stool/total number of feces granules X100%) and the minimum volume threshold of abdominal reflex (abdominal pain threshold) induced by rectal dilatation were observed. The content of colonic 5-HT was detected by using ELISA, and the expression of TPH1, SERT and 5-HT3R mRNAs and proteins were detected by using quantitative real time-PCR and Western blot, respectively. RESULTS: Compared with the blank control group, the minimum volume threshold of abdominal retraction reflex and the relative expression of SERT protein and mRNA were significantly decreased (P<0.01), and the loose stool rate, colonic 5-HT content, and relative expression of TPH1 and 5-HT3R proteins and mRNAs were notably increased in the model group (P<0.01). After moxibustion, both the decrease of minimum volume threshold and SERT protein and mRNA expressions and the increase of loose stool rate, colonic 5-HT content and TPH1 and 5-HT3R protein and mRNA expressions were reversed (P<0.01). CONCLUSION: Moxibustion of ST25 and ST37 can relieve abdominal hypersensitivity and diarrhea in IBS-D model rats, which is related to its effects in down-regulating colonic 5-HT content and expression of TPH1 and 5-HT3R proteins and mRNAs and in up-regulating expression of SERT protein and mRNA (regulating 5-HT/5-HT3R signaling)．.

[Effect of moxibustion on expression of RAGE and LRP-1 and neuronal ultrastructure of frontal cortex and hippocampus in vascular dementia rats].

OBJECTIVE: To explore the effect of moxibustion of acupoints of Governor Vessel on learning-memory ability and expression of the receptor for advanced glycation end products (RAGE), low density lipoprotein (LDL) receptor related protein-1 (LRP-1), ß-amyloid precursor protein (APP) and neuronal ultrastructure of the frontal cortex and hippocampus in vascular dementia (VD) rats, so as to investigate its underlying mechanisms in relieving VD. METHODS: A total of 24 male SD rats were randomized into normal, model, and moxibustion groups (n＝8 rats in each group). The VD model was established by occlusion of the bilateral common carotid arteries for 20 min and reperfusion for 10 min which was repeated for 3 times. Moxibustion was applied to "Baihui" (GV20), "Dazhui"(GV14) and "Fengfu"(GV16)for 30 min, once daily for 4 weeks. The learning-memory ability was evaluated by using Morris water maze tests. At the end of experiments, the frontal lobe of cerebral cortex and hippocampus tissues were collected for detecting the expression of RAGE and LRP-1 proteins with Western blot, and RAGE, LRP-1 and APP mRNAs with quantitative real-time PCR, respectively. The ultrastructure of neurons in the frontal cortex and hippocampal CA1 region was observed with transmission electron microscopy. RESULTS: Following modeling, Morris water maze tests showed that the average escape latency of the model group and moxibustion group was significantly prolonged on the 4th day of modeling (P<0.01). The expression levels of RAGE protein and mRNA and APP mRNA were significantly increased (P<0.01), while those of LRP-1 protein and mRNA in the cortex and hippocampus remarkably decreased in the model group relevant to the normal group (P<0.01). Following moxibustion, modeling-induced increase of expression of RAGE protein and mRNA and APP mRNA, and down-regulation of expression of LRP-1 protein and mRNA were reversed in the moxibustion group relevant to the model group (P<0.01). Results of electron microscopy showed dilation of the mitochondria with disappearance of the cristae, partial vacuolar degeneration or dissolved external membrane, and cytoplasmic edema with basic disappearance of the rough endoplasmic reticulum and glycogen particles in neurons of the frontal cortex and hippocampal CA1 region after modeling, which was relatively milder in the moxibustion group. CONCLUSION: Moxibustion of acupoints of the Governor Vessel may reduce the content of APP in the frontal cortex and hippocampus by regulating the expression of RAGE and LRP-1 proteins and mRNA in VD rats.

[Professor CHU Hao-ran's experience of acupuncture and moxibustion of regulating spleen-stomach and differentiating meridians-collaterals].

Professor CHU Hao-ran successively followed famous doctors of acupuncture and spleen-stomach disease, such as ZHOU Mei-sheng, inherited their academic thoughts and clinical experience, and studied the classics to summarize and propose the clinical academic proposition regulating spleen-stomach, differentiating meridians-collaterals. In clinical practice, professor CHU focuses on individual differences of patients, carefully examines syndrome and refines acupoint selection; he pays attention to regulating spleen-stomach, and actively uses Zusanli (ST 36); he simultaneously uses acupuncture-moxibustion and acupoints with efficacy; he inherits traditional reinforcing and reducing methods, and extends the scope of acupoint diagnosis and treatment, while he emphasizes keeping spirit and treating spirit, and the combination of mind and qi, in order to improve clinical diagnosis and treatment effect.

[Treatment of Vascular Cognitive Impairment by "Huayu Tongluo" Moxibustion].

OBJECTIVE: To observe the therapeutic effect of "Huayu Tongluo"(blood stasis-removing and meridian-collateral-dredging) moxibustion for vascular cognitive impairment(VCI) patients and changes of insulin like growth factor -1(IGF-1) levels in serum after the treatment. METHODS: Sixty patients with VCI were randomly divided into medication (control) and moxibustion groups (n＝30 in each group). Cotton cloth-separated moxibustion was applied to Baihui (GV 20) and Shenting (GV 24), and conventional moxibustion applied to Dazhui (GV 14) and Yongquan (KI 1) for 30 min, once daily, 6 times a week and for 30 days. Patients of the control group were treated by oral administration of Donepezil hydrochloride at the dose of 5 mg/night for 30 days. The core symptoms of traditional Chinese medicine (TCM), mini-mental state examination(MMSE), activity of daily living(ADL) and Montreal cognitive assessment(MoCA) scales were used to assess the therapeutic effect after the treatment. The content of serum IGF-1 was determined by ELISA. RESULTS: Of the two 30 cases in the control and moxibustion groups, 9 and 17 experienced marked improvement, 13 and were effective, 8 and 3 ineffective, with the effective rates being 73.33% and 90.00%, respectively. The effective rate in the moxibustion group was obviously higher than that in the control group (P<0.05). After the treatment, the TCM symptom scores were significantly decreased, and the MMSE, ADL and MoCA scores considerably increased in both groups compared with those of their own individual pre-treatment (P<0.01). The TCM symptom score of the moxibustion group was significantly lower, and the MMSE and ADL scores were obviously higher than those of the control group (P<0.01). The serum IGF-1 content in both groups was significantly increased after the treatment relevant to that of their own individual pre-treatment (P<0.01), and was obviously higher in the moxibustion group than in the control group (P<0.01). No significant difference was found between the two groups in the MoCA score after the treatment (P>0.05)．. CONCLUSION: "Huayu Tongluo" moxibustion has a positive effect for patients with VCI, which may be associated with its effect in up-regulating serum IGF-1 level.

[Effects of electroacupuncture on learning-memory ability and expression of hippocampal vascular endothelial growth factor (VEGF), VEGF receptor 1 and 2 genes in vascular cognitive impairment rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dazhui" (GV 14), "Baihui" (GV 20), etc. on learning-memory ability and expression of vascular endothelial growth factor (VEGF) mRNA, VEGF receptor 1 (VEGFR-1/Flt-1) mRNA, and VEGFR-2 (Flk-1) mRNA in the hippocampus in vascular cognitive impairment (VCI) rats so as to reveal its mechanism underlying improvement of VCI. METHODS: A total of 60 Wistar rats were randomly divided into sham operation, VCI model, EA and medication groups (n=12 in each group). The VCI model was established by occlusion of the bilateral vertebral arteries and bilateral cervical arteries. EA (2 Hz/20 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14), "Shuigou" (GV 26) and "Shenting" (GV 24) for 20 min, once daily for 20 days. Rats of the medication group were treated by intragastric perfusion of Aniracetam capsules (0.0625 g/kg),once daily for 20 days. The rats' learning-memory ability was detected by step-down test. The expression levels of VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA in the hippocampus were detected by RT-PCR, and the neurological deficit scores were assessed by Zea Longa (0-4 scaling) method. RESULTS: Compared with the sham operation group, rats of the model group showed a significant increase in reaction time and error number and decrease of escape latency (reduction of learning-memory ability), and increase in neurological deficit score, and in expression levels of hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA (all P<0.01). After EA treatment, in comparison with the model group, the learning-memory ability and hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA were apparently increased, neurological deficit score were markedly decreased in the EA group (all P<0.01). The effects of EA treatment was obviously superior to those of medication in raising learning-memory ability and up-regulating hippocampal VEGF mRNA and Flt-1 mRNA expression levels, and in reducing neurological deficit score (all P<0.05). CONCLUSION: EA intervention can apparently up-regulate hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA expression in VCI rats, which may contribute to its effect in improving learning-memory ability, possibly by promoting neovasculization.

[Analysis on therapeutic effect of bird-pecking moxibustion combined with western medicine for treatment of infantile hand, foot and mouth disease].

OBJECTIVE: To observe therapeutic effects of bird-pecking moxibustion in children of hand, foot and mouth disease, and to analyze the mechanism. METHODS: Seventy-five children of hand, foot and mouth disease were randomly divided into 3 groups, a combined moxibustion and medicine group (n = 22), a Chinese medicine group (n = 29), and a western medicine group (n = 24). The combined moxibustion and medicine group was treated with bird-pecking moxibustion combined with routine western medicine, the Chinese medicine group with oral administration of Chinese medicine and routine western medical therapy, and the western medicine group with routine western medicine. After treatment of 7 days, the therapeutic effects on skin rash, oral herpes, constipation or loose stool, dyspepsia and anorexia, etc. were comprehensively assessed, and their therapeutic effects were compared. RESULTS: The total effective rate was 95.5% in the combined moxibustion and medicine group, 86.2% in the Chinese medicine group, and 83.3% in the western medicine group, the former being significantly better than those of the other two groups (both P < 0.05). The combined moxibustion and medicine group was significantly better than the other two groups in the relieving time of skin rash, oral herpes, constipation or loose stool, dyspepsia and anorexia, etc. (all P < 0.05) CONCLUSION: The combined moxibustion and medication can effectively improve symptoms of the digestive tract, shorten duration of disease, reduce pain in the patient with hand, foot and mouth disease.