Analyzing the potential mechanism of Buyang Huanwu decoction for the treatment of salt-sensitive hypertension based on network pharmacology and in vivo experiments

Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.

Bo’s abdominal acupuncture treatment for adult-onset Still's disease:A case report

BACKGROUND Adult-onset Still's disease(AOSD)is a rare autoinflammatory disease charac-terized by nonspecific symptoms such as fever,rash,sore throat and arthralgia.This paper reports a clinical case of AOSD successfully treated with Bo’s abdo-minal acupuncture(BAA).CASE SUMMARY We report a 20-year-old man who suffered from cold exposure,presenting with high fever,rash,sore throat,arthralgia,and elevated erythrocyte sedimentation rate,leukocytosis with neutrophilic predominance,elevated ferritin,elevated C-reactive protein,and negative rheumatoid factors.He was diagnosed with AOSD based on the Yamaguchi criteria.After treatment with traditional Chinese medi-cine(TCM)decoction and prednisone acetate tablets,there was some alleviation of sore throat,joint and muscle pain,and fever,but he still had persistent low-grade fever,rash,sore throat and arthralgia.He went to the TCM acupuncture outpatient department to receive BAA.Abdominal acupoints Zhongwan(CV12),Xiawan(CV10),0.5 cm below Xiawan(CV10),Qihai(CV6),Guanyuan(CV4),bilateral Qixue(KI13),bilateral Huaroumen(ST24),bilateral Shangfengshidian(AB1)and bilateral Daheng(SP15)were selected.After 3 months treatment,all symptoms disappeared,and the laboratory examination returned to normal levels.He did not take glucocorticoids or nonsteroidal anti-inflammatory drugs afterwards,and no relapse was observed during the 3-year follow-up period.CONCLUSION BAA can be used as a complementary medical approach for treatment of AOSD.

Enhanced expression of epidermal growth factor receptor gene in gastric mucosal cells by the serum derived from rats treated with electroacupuncture at stomach meridian acupoints

AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress-induced gastric mucosal injury in rat model was established by water-immersion and restrained stress methods. 52 rats were randomly divided into: normal group (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were separated by pronase-EDTA digestion method and incubated with serum. The EGFR gene expression in gastric mucosal cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group (0.6860 ± 0.0594), the serum derived from rats of the stomach group (1.2272 ± 0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 ± 0.0387, P = 0.00 < 0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal cells. Such tendency existed in the model group (0.7104 ± 0.0457) but with no signifi cant difference (P = 0.495 > 0.05) and in model serum group (0.8516 ± 0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the EGFR gene expression in stomach serum group was significantly higher than that in gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows that serumderived from rats treated with electroacupuncture at stomach meridian acupoints can distinctly increase the EGFR gene expression of gastric mucosal cells. Therefore, there is certain meridian specificity in the serum, which could provide a proof for the TCM theory “particular relation between meridian and internal organ”.

Pre-moxibustion and moxibustion prevent Alzheimer's disease

The Alzheimer’s disease model in Wistar rats was established by injection of amyloid β-peptide （Aβ1-42 ） into the hippocampal CA1 region. Rats were treated with suspended moxibustion on Baihui （GV20） and Shenshu （BL23） acupoints. Prior to and post Aβ1-42 exposure. Results showed no evidence of apoptosis in hippocampal neurons, a significantly reduced apoptosis rate of neurons and improved learning and memory abilities were observed in the Alzheimer’s disease model. In particular, moxibustion prior to Aβ1-42 exposure was more effective than moxibustion after Aβ1-42 exposure in protecting the neuronal structure and lowering the apoptosis rate. Our findings indicate that a combination of preventive and therapeutic moxibustion has a beneficial effect for the tion of Alzheimer’s disease development.

Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression

Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase （JNK）, protein kinase B （Akt）, and p38 mitogen-activated protein kinase （p38） signal transduction pathway, and also regulate various apoptotic cascades. JNK and p38 promote apoptosis, but Akt protects against apoptosis, in hippocampal neurons. However, changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood. Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group （P 〈 0.05）. No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups, and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups （P 〉 0.05）. These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.

Clinical Application of the Yang-Activating Method in Acupuncture Treatment

According to the theory of traditional Chinese medicine (TCM), yang-qi is considered to play a leading role in the human body. It has the function of defending the organism, warming the body surface and moisturizing the muscles so as to ensure normal physiological functions.

Research Progress on Molecular Mechanism of Moxibustion in the Treatment of Ankylosing Spondylitis

As an important part of traditional Chinese medicine (TCM) nursing technology, moxibustion plays a unique role in improving the symptoms of ankylosing spondylitis (AS). The research on the mechanism of moxibustion intervention in AS mainly focuses on anti-inflammatory effects, immune regulation, bone metabolism regulation, intestinal flora regulation, and so on. Molecular medicine is of great significance to further clarify the mechanism of moxibustion intervention in AS. However, there are still some problems in the research on the molecular mechanism of moxibustion intervention in AS: the existing biomedical research methods only explore from a specific field and lack the exploration of moxibustion-targeted molecules based on biomedical network. In the future, the molecular network effect of moxibustion on AS can be discussed comprehensively and systematically with the help of omics technology and the construction of biological information interaction network between omics. The effect of moxibustion on upstream osteogenic transcription factors and related signaling pathways such as WNT, β-catenin, and BMP/Smads is not yet clear. Future research can focus on the relevant signal targets of bone reconstruction and clarify the mechanism of moxibustion against the new bone formation. In addition, there is a lack of research on the molecular mechanism of moxibustion in the treatment of AS from the perspective of metabolites. It is necessary to further explore the mechanism of moxibustion in the treatment of AS with the help of metabonomics technology.

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Acupuncture at the Taixi(KI3) acupoint activates cerebral neurons in elderly patients with mild cognitive impairment

Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.

Mastering Specificity of Acupoints Based on Clinical Verses of Acupuncture and Moxibustion

The classic verses of acupuncture and moxibustion are the ancient records of the content of acupuncture and moxibustion in the form of songs, including meridians, acupoints, techniques, clinical treatment, medical cases, etc. About 20 articles among them summarize the valuable clinical experience of ancient famous acupuncturists. The verses are extremely useful. They prescribe a method of treating disease in which very few acupoints are selected (mostly only one, but sometimes two or three points). The point selection is based on the acupuncturists' advanced mastery of acupoint specificity, which practitioners today must learn. Unfortunately, because of the verses' simple expression, it is difficult for modern readers to understand them in depth. As a result, undergraduates majoring in acupuncture and moxibustion are no longer required to study the verses(1,2) This means that modern acupuncturists are unfamiliar with these verses and seldom use them in clinic practice. This greatly limits the application and promotion of the verses.

Long-Term Continuous Light Exposure Affects Body Weight and Blood Glucose Associated with Inflammation in Female Rats

Studies have indicated that night lights interfere with the circadian rhythm in the human body and threaten human health. Our previous studies indicated that continuous light exposure severely damages the reproductive endocrine system of female rats resembles polycystic ovary syndrome in women. In this study, we used the continuous measurement method to observe changes in the basal physiological indicators of female rats in an abnormal light exposure environment. Our study results indicated that in female rats: 1) the body temperature first continuously and gradually increased followed by a gradually decrease;2) the increase in body weight slowed down at the late stage of the experimental process;3) the random blood glucose level increased, and the fasting serum insulin level decreased;and 4) the serum C-reactive protein level increased. Our study investigated for the first time the correlation between the duration of continuous light exposure in female rats and the continuously measured basal physiological indicators and preliminarily discussed the effect of continuous light exposure on female basal metabolism and the possible inflammation mechanism. We propose that long-term continuous exposure to night lights in females severely damages their immune and metabolic systems.

A STUDY OF THE CHARACTERISTICS OF γ-GLUTAMYLTRANSPEPTIDASE OF HUMAN ESOPHAGEAL CANCER

γ-Glutamyltranspeptidase (γ-GT) from human esophageal cancer, normal esophageal mucosa and normal kindney were partially purified and their biochemical and immunological properties were studied. (1) The γ-GT activity of esophageal cancer was higher than that of normal mucosa, yet still much lower than that of normal kidney. (2) The Michaelis constant and optimum pH of esophageal cancer γ-GT were the same as those of normal kidney tissue. (3) After staining of γ-GT activity, two molecular clusters, i.e. 100kD and 380kD γ-GT were shown in esophageal cancer by 4-20% linear gradient PAGE and the lOOkD γ-GT showed higher activity. (4) The γ-GT of esophageal cancer was immunologically identical with normal enzyme in double immunodif-fusion and immunoelectrophoresis. (5) In double lectin-diffusion, affinity column and crossed immuno-affino-electrophoresis, it was demonstrated that the carbohydrate components of γ-GT from esophageal cancer were heterogeneous and rich in D-Mannose, D-Glucose and N-Acetyl-Glucosamine. The relationship between the appearance of 100kD γ-GT cluster and the heterogeneous carbohydrate components will be further studied.

Quality assessment of randomized controlled trials reporting on knee osteoarthritis treated with warming needle moxibustion

OBJECTIVE: To evaluate the quality of randomized controlled trials(RCTs) testing the efficacy of warming needle moxibustion on knee osteoarthritis(KOA).METHODS: Nine databases were searched systematically including: the Cochrane Library(1/1993-10/2012), Pub Med(1/1980-10/2012), EMBASE(1/1990-10/2012), SCI Expanded(1/1986-10/2012), Science Direct(1/1979-10/2012), Chinese Biomedical Literature Database disc(1/1978-10/2012), China National Knowledge Infrastructure Database(1/1979-10/2012), China Science and Technology Journal Database(a full text issue database of China, 1/1989-10/2012), and Wanfang Database(a full text issue database of China, 1/1990-10/2012). Traditional reference retrieval was also conducted. Language was limited to Chinese and English. We identified 37 RCTs that used warming needle moxibustion as an intervention and they were assessed with the Consolidated Standards for Reporting of Trials Statement 2010(CONSORT 2010) and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010(STRICTA 2010).RESULTS: Of the 37 reports, only seventeen(45.95%) mentioned the random allocation of sequence methods, nine used unacceptable methods, and only one(2.70%) gave the description of the mechanism of allocation concealment. One study(2.70%) mentioned blinding, one(2.70%) had a sample size calculation, and twenty-three(62.16%) used reasonable statistical methods. Thirteen(35.14%) described the background and reason for the RCTs, three(8.11%) gave a description of lost or eliminated patients, and two(5.41%) reported accidental situations. Only three(8.11%)gave analysis of the RCT limitations. No report mentioned intentional analysis.CONCLUSION: The quality of the RCTs assessed in this study was from moderate to low. The design of RCTs, the methods of statistical analysis, and the description of reports information needs to be improved. CONSORT 2010 and STRICTA 2010 should be used to standardize the reporting of acupuncture RCTs in the future.

Neuroprotective Effects of Electroacupuncture on Hypoxic-Ischemic Encephalopathy in Newborn Rats Are Associated with Increased Expression of GDNF-RET and Protein Kinase B

Objective： To explore the neuroprotective effects of electroacupuncture （EA） on hypoxic-ischemic encephalopathy （HIE） and to further investigate the role of glial cell line-derived neurotrophic factor （GDNF） family receptor member RET （rearranged during transfection） and its key downstream phosphatidylinositol 3 kinase （PI-3K）/protein kinase B （Akt） pathway in the process. Methods： A total of 220 seven-day-old SD rats （of either sex, from 22 broods） were randomly divided into two groups, one （30 rats） for sham-surgery group and the other （190 rats） for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui （GV 20）, Dazhui （GV 14）, Quchi （LI 11） and Yongquan （KI 1） acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin （HE） staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction （RT-PCR） and western blot analysis, respectively. Results： EA could ameliorate neurologic damage of the first somatic sensory area （SITr） and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. Conclusion： EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process.

Curative effect of acupuncture on quality of life in patient with depression： a clinical randomized single-blind placebo-controlled study

OBJECTIVE:To evaluate the effect of acupuncture on the quality of life in patients with depression by clinical randomized single-blind placebo-controlled study.METHODS:one hundred and sixty-three cases of depression according with the inclusion criteria were randomly divided into a group of acupuncture dredging liver and regulating flow of theosophy(group 1),a group of acupoint shallow stab(group 2)and a group of non-acupoint shallow stab(group 3)at 1∶1∶1 ratio,and treated with acu-puncture,moxibustion,and intradermal embedding of needle,twice a week,for a total of 12 weeks.Scale of Quality of Life(SF-36)was used to measure the scores at four different time points and evaluate the effect of acupuncture on the quality of life of the patients with depression.RESULTS:At each time point after treatment,in scores of the 8 items,physical function,physical role,bodily pain,general physical condition,energy,social function,emotional function and mental health there were statistically significant differences among the 3 groups(P<0.0125).CONCLUSION:Acupuncture can effectively improve the quality of life of patients with depression.

Comparison of the Effects of Traditional Box-Moxibustion and Eletrothermal Bian-Stone Moxibustion on Volume of Blood Flow in the Skin

Objective: To investigate and compare the effects of Electrothermal Bian-stone moxibustion and traditional box-moxibustion on capillary blood perfusion in the body surface. Methods: Twenty healthy subjects, 18 females and 2 males, aged averagely 36 years, were enrolled in this experiment. The traditional box-moxibustion and electrothermal Bian-stone moxibustion were respectively given on the hypogastrium around Guanyuan (CV 4), and the changes of local capillary blood perfusion in the body surface were investigated with Laser Doppler Perfusion Imaging (LDPI). Results:The traditional box-moxibustion was superior to the electrothermal Bian-stone moxibustion in the transient increasing effect in whole body and the long-term increasing effect in the local area of moxibustion on capillary blood perfusion; but for both methods, the increasing effect on the capillary blood perfusion in the local area of moxibustion was same. Conclusion: Electrothermal Bian-stone moxibustion can not completely take the place of the traditional box-moxibustion; but for some disorders with local pain, they possibly have the same effects.

Effect of electroacupuncture at Ximen(PC 4) and Hegu(LI 4) on expression of Akt in rats with myocardial ischemia-reperfusion injury

OBJECTIVE: To investigate the effect of electroacupuncture(EA) at acupoints on the pericardium meridian on the expression of phosphorylated Akt(p-Akt) protein in rat myocardium after ischemia and reperfusion.METHODS: Seventy Wistar rats were evenly randomized into seven groups: the sham operation group(group A), ischemia-reperfusion model Ⅰgroup(group B), ischemia-reperfusion model Ⅱgroup(group C), EA at Neiguan(PC 6) group(group D), EA at Ximen(PC 4) group(group E), EA at Hegu(LI 4) group(group F), and LY294002 + EA at Neiguan(PC 6) group(group G). All processes were monitored by electrocardiography. In group A, the left anterior descending coronary artery was only threaded without ligation for 100 min. In group B,the left anterior descending coronary artery was ligated for 40 min and reperfused for 60 min. The left anterior descending coronary artery in group C was ligated for 40 min and reperfused for 100 min.Groups D, E, and F received EA for 20 min before undergoing ischemia for 40 min, and then received EA for 20 min before undergoing reperfusion for 60 min. Before modeling, group G was injected with LY294002(0.3 mg/kg) into the tail vein, and then underwent the same intervention as the other EA groups. After reperfusion, myocardial tissue from the left cardiac ventricle was collected to enable Western blot analysis of the p-Akt level, and analysis of electrocardiographic changes.RESULTS: In groups B and C, electrocardiography showed obvious elevation of the ST-segment Ⅱlead(ECG-STⅡ), while the ECG-STⅡvalues were significantly lower in groups D, E, and G(P < 0.01). The p-Akt levels in groups D and E were significantly greater than those in groups B and C(P < 0.01).Compared with all other groups, group G showed a significantly different expression of p-Akt(P < 0.01).CONCLUSION: The expression of p-Akt protein in cardiomyocytes was significantly greater in rats that were injected with LY294002 and received EA at Ximen(PC 4) compared with all other groups.This suggests that EA at Ximen(PC 4) resulted in activation of the phosphoinositide 3-kinase/Akt signaling pathway and phosphorylation of Akt.

Role of Parameter Setting in Electroacupuncture: Current Scenario and Future Prospects

Acupuncture is an ancient therapeutic method based on the theory of Chinese medicine(CM). Traditional acupuncture has many limitations;it is subjective and relies more on the experience of an acupuncturist, and the efficacy is sometimes irreproducible. In contrast, electroacupuncture(EA) has special characteristics in terms of objectivity and stability, thereby gaining considerable attention. Parameter setting plays a crucial role in EA practice. The current paper summarizes the current situation and limitations of parameter setting in EA practice. Objectification is the tendency and future of CM as well as EA. With the development of computerized technologies, such as wearable sensors, vast data, and artificial intelligence, CM syndromes can be successfully objectified. We propose the development of a novel self-feedback-adjust EA system, which may improve the parameter setting in EA and be beneficial to both the patients and clinicians.

Effect of electroacupuncture pretreatment on the protein expression of c-fos in fastigial nucleus and lateral hypothalamus area in rats with acute myocardial ischemia-reperfusion injury

Objective:To observe the effect of electroacupuncture(EA)pretreatment on the protein expression of c-fos in fastigial nucleus(FN)and lateral hypothalamus area(LHA)in rats with acute myocardial ischemia-reperfusion injury(MIRI),and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction.Methods:Seventy Sprague-Dawley rats were randomly divided into a sham operation group,a model group,an EA-Heart Meridian group and an EA-Lung Meridian group,with 14 rats in each group;an LHA lesion plus EA-Heart Meridian group(LHA+EA-Heart Meridian group)and a FN lesion plus EA-Heart Meridian group(FN+EA-Heart Meridian group),with 7 rats in each group.Except the sham operation group,the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups.In the three groups with EA-Heart Meridian treatment,Shenmen(HT 7)and Tongli(HT 5)were selected;Taiyuan(LU 9)and Lieque(LU 7)were selected in the EA-Lung Meridian group.All the EA groups received EA stimulation prior to modeling,with 1 mA in current intensity and 2 Hz in frequency,20 min each time,once a day for a total of 7 d.The sham operation group and the model group did not receive EA stimulation.The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score.The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method.Results:Compared with the sham operation group,the ST-segment deviation,cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group(all P<0.05).Compared with the model group,the ST-segment deviation,cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group(all P<0.05).Compared with the EA-Heart Meridian group,the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group,LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group(all P<0.05);the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group(both P<0.05);the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group(both P<0.05).Conclusion:FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions,and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

Effects of electroacupuncture on angiogenesis and cortical VEGF and BDNF expression in rats with focal cerebral ischemia

Objective To observe the effect of electroacupuncture(EA)of“concurrent treatment of the brain and heart”on angiogenesis and cortical vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)in rats with focal cerebral ischemia,and to explore the mechanism of EA in cerebral ischemia treatment.Methods A total of 108 Sprague-Dawley rats,27 rats were randomly selected as the sham-operation group,and the rest rats received the right middle cerebral artery occlusion operation for model preparation firstly,and then were divided into a model group,a traditional acupoint group,and a concurrent treatment of the brain and heart group,with 27 rats in each group.In the sham-operation group,only the carotid artery was isolated.EA at Shuigou(CV26),Quchi(LI11),Hegu(LI4),and Zusanli(ST36)in the traditional acupoint group,and EA at Fengfu(GV16),Baihui(GV20),Xinshu(BL15),and Neiguan(PC6)in the concurrent treatment of the brain and heart group were performed 4 h after the operation,once a day,for 14 consecutive days.Rats in the sham-operation group and the model group were identically fixed without any treatment.Before and after treatment,the modified neurological severity score(mNSS),regional cerebral blood flow(rCBF),and CD34 positive expression by immunohistochemistry were measured.The positive protein expression levels of VEGF and BDNF were detected by immunofluorescence,and the mRNA expression levels of VEGF and BDNF were detected by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Results Compared with the sham-operation group,the mNSS,rCBF,and ischemic side cortical micro-vessel density(MVD)decreased,and the protein and mRNA expression levels of VEGF and BDNF increased in the model group(P<0.01).Compared with the model group,the mNSS of the two EA groups decreased,and the mNSS of the concurrent treatment of the brain and heart group was lower than that of the traditional acupoint group on the 14th day(P<0.05).Compared with the model group,the rCBF in the two EA groups increased,and the rCBF reached the highest on the 14th day(P<0.05 or P<0.01),and the rCBF in the concurrent treatment of the brain and heart group was higher than that in the traditional acupoint group(P<0.05);the MVD of the two EA groups was higher than that of the model group,and the MVD of the concurrent treatment of the brain and heart group was higher than that of the traditional acupoint group on the 7th and 14th days(P<0.05 or P<0.01).Compared with the model group,the protein and mRNA expression levels of VEGF and BDNF in the two EA groups increased(P<0.01).The VEGF expression level was the highest on the 7th day in the concurrent treatment of the brain and heart group(P<0.05),and the BDNF expression level was higher on the 7th and 14th days than on the 3rd day(P<0.05).The mRNA expression levels of VEGF and BDNF in both EA groups reached the highest on the 7th day(P<0.05 or P<0.01).Conclusion EA therapy can up-regulate the VEGF and BDNF expression levels and increase the rCBF in the cortex of rats with focal cerebral ischemia,which may be one mechanism of EA in the cerebral ischemia treatment.The therapeutic effect is accumulated with the effective time,and the concurrent treatment of the brain and heart group is superior to the traditional acupoint group in promoting angiogenesis.