Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics.

PURPOSE: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. METHODS: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. CONCLUSIONS: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

[Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. METHODS: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were determined. RESULTS: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CONCLUSION: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1ß and IL-6 in myocardial tissue.

Involvement of Interleukin-1 ß/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 ß (IL-1 ß), insulin-like growth factor 1 (IGF-1), and transforming growth factor ß 1 (TGF- ß 1) to the effects. METHODS: Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 ß, TGF- ß 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively. RESULTS: After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 ß, IGF-1, TGF-ß 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 ß, IGF-1, TGF-ß 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01). CONCLUSION: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 ß/IGF-1-TGF- ß 1-MMP9 pathway.

Synergistic and Attenuating Effect of Electroacupuncture on Aconitine in Improving Heart Failure and Its Calcium Regulation Mechanism.

Objective: The objective is to observe the synergistic and attenuating effect of electroacupuncture (EA) on aconitine (ACO) in improving heart failure (HF) and to explore its underlying mechanism for calcium regulation. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: normal control (NC) (n = 6), HF(n = 6), ACO (n = 6), and ACO + EA (n = 6). The maximum rates of left ventricular pressure rising and declining (±dp/dtmax), arrhythmia, the left ventricular systolic pressure (LVSP), ejection fraction (LVEF), and fractional shortening (LVFS) were measured by physiological recorder and ultrasound, respectively. Protein expressions of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a), phospholamban (PLB), and Na+-Ca2+ exchange (NCX1) in the left ventricle tissue were detected by fluorescence immunoblotting. Results: Compared with the NC group, LVSP, ±dp/dtmax, LVEF, and LVFS were decreased in the HF group; compared with the HF group, LVSP, ±dp/dtmax, LVEF, and LVFS were significantly increased in the ACO + EA group. Compared with the ACO group, the incidence and the degree of arrhythmia were significantly reduced in the ACO + EA group. Compared with the NC group, the activity of SERCA2a was decreased, and the expression of PLB and NCX1 was enhanced in the HF group; compared with the HF group and ACO group, the activity of SERCA2a was increased, and the expression of PLB and NCX1 was significantly attenuated in the ACO + EA group. Conclusions: EA plays a synergistic and attenuated role in ACO improving HF, and the mechanism may be related to the enhancement of the SERCA2a activity and the decrease of the expression of PLB and NCX1 in cardiomyocytes.

[Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS). METHODS: Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular. RESULTS: Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group. CONCLUSION: EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

[Preliminary study on mechanism of electroacupuncture with the involvement of SERCA2a/PLB on the synergistic and attenuated effect of aconitine in treatment of heart failure].

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure. METHODS: Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 µg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected and arrhythmia types were observed and scored. SERCA2a protein and PLB protein expressions in left ventricular myocardial tissue of rats were detected by multiplex fluorescence Western blot. RESULTS: Compared with the control group, LVSP and ±dp/dtmax all were decreased after modeling and at each time point after intervention in the model group (P<0.01). Compared with the model group, ±dp/dtmax was increased in the aconitine group and the EA group at 1 min after intervention (P<0.01, P<0.05), +dp/dtmax was increased at 10 to 60 min after intervention in the aconitine group and at 20 to 60 min after intervention in the EA group (P<0.01, P<0.05), LVSP was increased at 1 min after intervention in the EA group (P<0.01), while LVSP and ±dp/dtmax were all increased at 1 to 60 min after intervention in the EA plus aconitine group (P<0.01, P<0.05). Compared with the aconitine group, LVSP and +dp/dtmax were increased at 1 min after intervention in the EA group (P<0.01, P<0.05), LVSP and ±dp/dtmax at 1 min after intervention while +dp/dtmax at 20 to 60 min after intervention were all increased in the EA plus aconitine group (P<0.01, P<0.05). Compared with the EA group, +dp/dtmax was higher at 10 to 60 min after intervention in the EA plus aconitine group (P<0.01). Compared with the model group, arrhythmia score was higher in the aconitine group (P<0.01). Compared with the aconitine group, arrhythmia score was lower in the EA group and the EA plus aconitine group (P<0.01). As compared with the control group, the expression of SERCA2a protein in the left ventricular cardiomyocytes was decreased (P<0.01), while the expression of PLB protein was increased in the model group (P<0.01). Compared with the model group, the expression of SERCA2a protein was increased in both the EA group and the EA plus aconitine group (P<0.05, P<0.01), and PLB protein expression was decreased in each intervention group respectively (P<0.01, P<0.05). As compared with the EA group and the aconitine group, the expression of SERCA2a protein was increased and the expression of PLB protein was decreased in the EA plus aconitine group separately (P<0.05, P<0.01). CONCLUSION: The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.

[Observation on facilitation and attenuation effect of electroacupuncture combined with aconitine for treatment of heart failure in rats].

OBJECTIVE: To observe the influence of electroacupuncture(EA) combined with aconitine on the hemodyna-mics, echocardiogram, and arrhythmias in heart failure rats, so as to explore the facilitation and attenuation effects of EA combined with aconitine. METHODS: SD rats were randomly divided into control, model, aconitine and aconitine+EA groups, with 6 rats in each group. Propranolol hydrochloride was used to establish the heart failure model. Rats in the aconitine group were trea-ted with aconitine continuously for 1 h (40 µg/kg). Rats in the aconitine +EA group were given the same treatment as the aconitine group, meanwhile, EA (3 mA, 2 Hz/15 Hz) was applied at "Neiguan"(PC6) for 30 min. Left ventricular catheter and small animal ultrasound imaging system were used to observe the heart hemodynamic indexes such as left ventricular systolic pressure(LVSP), maximal rate for left ventricular pressure rising (+dp/dtmax), and maximal rate for left ventricular pressure declining (-dp/dtmax), ejection fraction (EF) and fractional shortening (FS). The incidence rate of arrhythmia and arrhythmia score was observed by electrocardiogram. RESULTS: Following modeling and compared with the control group, LVSP, +dp/dtmax, -dp/dtmax, EF and FS in the aconitine group all decreased(P<0.01) and maintained in the model group. The LVSP of rats in the aconitine group was higher than that of the model group at 15 min after administration of aconitine (P<0.05), and +dp/dtmax was higher at 15, 60 min after administration (P<0.05). Since 15 min after administration, EF and FS in the aconitine group were significantly higher than those of the model group (P<0.01, P<0.05). After EA intervention, compared with the aconitine group, LVSP, +dp/dtmax, -dp/dtmax in the aconitine+EA group were significantly increased (P<0.01, P<0.05) during administration and EF and FS in the aconitine+EA group significantly increased at the beginning of administration of aconitine and 30 and 60 min during administration (P<0.05, P<0.01). The incidence rate of arrhythmia was 100% in the aconitine group, and 50.0% in the rats of aconitine + EA group. The arrhythmia score of aconitine + EA group was significantly lower than that of aconitine group (P<0.05). CONCLUSION: Aconitine has a certain inotropic effect, but it is easy to cause arrhythmia. The combination of EA and aconitine can not only improve the contractile function of the heart in rats with heart failure, but also reduce the toxic reaction of aconitine.

ß-HB inhibits the apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis.

OBJECTIVE: Nerve damage can cause severe limb dysfunction and even leave a lifelong disability. The apoptosis of astrocytes may contribute to the nerve damage. In this research, we sought to investigate the effect of ß-HB on nerve damage in vitro. DESIGN: Astrocytes were treated with high glucose (HG) to mimic in vitro model of nerve damage. RT-qPCR and western blot were used to detect expressions of CREB, BDNF, Ki-67, PCNA, Bax, Bcl-2 and cleaved caspase 3 in astrocytes, respectively. MTT was used to measure the cell viability. In addition, flow cytometry was used to detect the cell apoptosis. RESULTS: ß-HB significantly promoted the proliferation and inhibited apoptosis in HG-treated astrocytes. Results showed that of PCNA and Bcl-2 were upregulated, and Bax and cleaved caspase 3 were downregulated after ß-HB stimulated in HG-treated astrocytes. In addition, HG-induced inhibition on BDNF expression in astrocytes was notably reversed by ß-HB. Furthermore, ß-HB promoted the growth and inhibited apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis. CONCLUSION: ß-HB promotes the growth and inhibits the apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis, which may serve as a new target for treatment of nerve damage.

Acupuncture for Paclitaxel-Induced Peripheral Neuropathy: A Review of Clinical and Basic Studies.

Paclitaxel-induced peripheral neuropathy (PIPN) is a common and intractable side effect of the conventional chemotherapeutic agent paclitaxel. Acupuncture has been reported as an effective alternative therapy in treatment of PIPN in both basic studies and clinical trials. However, there is a lack of comprehensive surveys to summarize the action of acupuncture in management of PIPN. In this review, we briefly demonstrate the basic pathology of PIPN, which includes the activation of ion channels, mitochondrial dysfunction, disruption of axonal transport and also neuro-inflammatory involvement. Meanwhile, we review both the clinical and basic studies as an emphasis to give a general overview of the therapeutic effect of acupuncture against PIPN. Finally, we summarize the current known mechanisms underlying the action of acupuncture against PIPN mainly at peripheral and spinal levels, which include various neurotransmitters, multiple receptors, different types of enzymes and molecules. In conclusion, acupuncture could be considered as a potential alternative therapy in treatment of PIPN, and further clinical and experimental studies are called for in the future.

[Characteristics of "deqi" and myoelectricity in different tissue structures of acupoint].

OBJECTIVE: To investigate the effect of acupuncture in different tissue structures on deqi and the electromyography of acupoint area. METHODS: Twenty healthy subjects, respectively accepted 4 kinds of needling stimulation, i.e. stimulating skin at Zusanli (ST36), stimulating ST36 with and without skin anesthesia using compound lidocaine cream, and stimulating at Dubi (ST35) without skin anesthesia. Deqi sensation of the acupuncturist and subjects were measured according to MGH Acupuncture Sensation Scale (MASS) during needling, and the myoelectricity around the acupoints was recorded simultaneously. The occurrence rate and intensity of the different deqi sensations, the relationship between the acupuncturist's and subjects' deqi sensations, and the integrated electromyogram (iEMG) were analyzed. RESULTS: Sharp pain and tingling were the main sensations during skin needling at ST36. Fullness, dull pain, soreness and acupuncturist's tightness were the main sensations during needling with or without skin anesthesia at ST36. Fullness was the main sensation during needling at ST35, while the intensity was lower than that during needling at ST36. A positive correlation in the intensity was found between subjects' fullness and acupuncturist's tightness during needling with or without skin anesthesia at ST36. The subjects' fullness appeared earlier about 5 seconds than acupuncturist's tightness. The iEMGs during subjects' fullness and acupuncturist's tightness were 2-3 times of that before needling. CONCLUSION: Deqi sensations such as subjects' fullness, dull pain, soreness and acupuncturist's tightness are mainly related to the activity of the muscles under the acupoints. Subjects' fullness and acupuncturist's tightness always appear together. Acupuncturist's tightness may be mediated by the muscle stretch reflex induced by needling stimulation.

Effects of Three Needling Manipulations of Zusanli (ST 36) on Deqi Sensations and Surface Myoelectricity in Healthy Participants.

OBJECTIVE: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS: The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Electroacupuncture ameliorates corticotrophin-releasing factor-induced jejunal dysmotility in a rat model of stress.

BACKGROUND: Central injection of corticotrophin-releasing factor (CRF) mimics the effect of stress on gastrointestinal (GI) responses, including inhibition of GI motility. This study was designed to explore the effects of electroacupuncture (EA) on disordered jejunal motility in a rat model of stress induced by intracisternal (IC) injection of CRF. METHODS: A stress model was established by IC injection of CRF in Sprague-Dawley rats. GI motility was evaluated by assessing gastric emptying (GE), gastrointestinal transit (GIT) and jejunal motility in vivo. EA was performed at ST36. The functional roles of CRF receptor subtype 1 and subtype 2 (CRFr1 and CRFr2) were examined by IC administration of the corresponding selective CRF antagonists. Protein expression of CRFr1 and CRFr2 in the hypothalamus and jejunum was detected by Western blotting. RESULTS: IC injection of CRF significantly inhibited GE, GIT and jejunal motility. EA treatment remarkably improved the disturbed GI motility. Intriguingly, the disordered jejunal motility induced by central CRF was abolished by IC injection of a selective CRFr2 antagonist, indicating the essential role of central CRFr2 in mediating the stress-induced jejunal motor disorder. EA at ST36 decreased central and peripheral expression of CRFr2, which might be one of the potential mechanisms underlying the beneficial effect of EA on jejunal dysmotility in this rat model of stress. CONCLUSION: This study suggested that EA at ST36 could ameliorate disordered jejunal motility induced by stress, and that this might be associated with the down-regulation of CRFr2.

Antihypertensive and Antifibrosis Effects of Acupuncture at PC6 Acupoints in Spontaneously Hypertensive Rats and the Underlying Mechanisms.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II - TGF-ß1 pathway.

[New thoughts about study on cholinergic anti-inflammatory pathway in mediating delaying effect of electroacupuncture on myocardial remodeling of chronic hypertension].

Chronic hypertension evoked aberrant myocardial remodeling is the main reason for progressive death from heart failure. It is of great clinical significance to find effective prevention and treatment methods to block this pathological process. It has been shown that imbalance of the autonomic nervous system (ANS) induced by chronic hypertension, i.e., hyper-excitation of sympathetic nerve system and suppression of parasympathetic (vagal) nerve system, activates immune cells-mediated inflammatory responses, and exacerbates the pathological remodeling of cardiac tissue. Except the negative inotropic outcomes, excitation of vagal nerves also has an anti-inflammatory effect which is mediated by activating the cholinergic anti-inflammatory pathway (CAIP). Previous studies showed that electroacupuncture (EA) could exert anti-hypertensive and systematic anti-inflammatory effects by increasing vagal activity. In addition, preliminary study from our lab demonstrated that EA was able to alleviate the pathological progress from hypertension to cardiac hypertrophy. However, the potential role of CAIP in restoring hypertension induced aberrant myocardial remodeling is still unknown. Herein, based on the alteration of ANS function in hypertension and EA's impact on vagal activity, we propose novel research ideas that EA could attenuate the pathological process of hypertension induced abnormal myocardial remodeling via activating CAIP.

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

PURPOSE: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway.

BACKGROUND AND PURPOSE: Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved. METHODS: Rats intraperitoneally received a cumulative dose of 8 mg/kg PTX (2 mg/kg per day) or vehicle control on alternate days (day 0, 2, 4 and 6). EA treatment (10 Hz, 1 mA) was applied at bilateral ST36 acupoints in rats once every other day on days 0-14. For sham EA, needles were inserted at ST36 acupoints without electrical stimulation. Mechanical allodynia was measured by mechanical withdrawal latency (MWL) of paws to a mechanical stimulus every 2 days. Protein expression of TLR4 and NF-κB p65, as well as TMEM119 and GFAP (indicators of microglia and astrocytes, respectively) in spinal cord was quantified by Western blot analysis. Levels of inflammatory cytokines IL-1ß and TNF-α in spinal cord and serum were detected by ELISA. RESULTS: Mechanical allodynia induced by PTX in both paws (right and left) of rats was significantly attenuated by EA but not sham EA treatment. In addition, EA, but not sham EA, inhibited the activation of both microglia (TMEM119) and astrocytes (GFAP) in lumbar spinal cord. Moreover, Western blot analysis revealed that protein expression of TLR4 and NF-κB in spinal cord was suppressed by EA but not sham EA treatment. PTX significantly increased inflammatory cytokines in spinal cord and serum, which were ameliorated by EA treatment but not by sham EA. CONCLUSION: These results indicate that EA treatment attenuates PTX-induced mechanical allodynia. The putative mechanism corroborating this finding could be related to the suppression of activated microglia and astrocytes in spinal cord, as well as the inhibition of the activated TLR4/NF-κB signaling pathway by EA treatment.

[Application of shear wave elastography in acupuncture research].

In recent years, a new technique of elastic quantization imaging, the ultrasound-based shear wave elastography (SWE) is arising, which has advantages of real-time, non-invasion, rapid imaging and strong repeatability, and quantifying the elastic properties of soft tissues including thyroid gland, breast, prostate, muscle tendon, ligament, etc.. It has been gradually applied to clinical and experimental researches of acupuncture and has an extensive application prospect. The present paper briefly introduces the application of SWE in accurately locating the acupoint, Deqi from needled acupoints, acupuncture manipulations, and evaluation of efficacy of acupuncture in the treatment of musculofascial diseases.

The Role of Adenosine A2b Receptor in Mediating the Cardioprotection of Electroacupuncture Pretreatment via Influencing Ca2+ Key Regulators.

OBJECTIVE: To investigate the roles played by A2b receptor and the key Ca2+ signaling components in the mediation of the cardioprotection of electroacupuncture pretreatment in the rats subjected to myocardial ischemia and reperfusion. METHODS: SD rats were randomly divided into a normal control (NC) group, ischemia/reperfusion model (M) group, electroacupuncture pretreatment (EA) group, and electroacupuncture pretreatment plus A2b antagonist (EAG) group. The ischemia/reperfusion model was made by ligation and loosening of the left descending branch of the coronary artery in all groups except the NC group. The EA group was pretreated with electroacupuncture at the Neiguan (PC6) point once a day for three consecutive days before the modeling. The elevation of the ST segment, arrhythmia scores, and myocardial infarction size of each group was measured. The relative expression levels of A2b, RyR2, SERCA2a, NCX1, P-PLB(S16)/PLB, and Troponin C/Troponin I proteins in the injured myocardium were detected by multiple fluorescence western blot. RESULTS: The level of ST segment, arrhythmia scores, and infarct size in the M group was significantly higher/larger than that in the NC group after ischemia and reperfusion, while all the three indices mentioned above in the EA group were significantly lower/smaller than those in the M group after reperfusion. The expression of the proteins of adenosine receptor 2b(A2b), ryanodine receptor 2(RyR2), and sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) in the EA group was significantly enhanced as compared with the M group, while in the EAG group, the contents of A2b were significantly lower than those in the EA group, and RyR2 was higher in the EAG group. In comparison with the NC group, the relative expression of NCX1 protein in M, EA, and EAG groups was not changed significantly. The ratio of phosphorylated phospholamban (P-PLB) over phospholamban (PLB) in the M group was significantly lower than that in the NC group, and the ratio in the EA group was significantly increased as compared with the M group, while the ratio of Troponin C/Troponin I in the EA group was significantly decreased in comparison with that in other groups. CONCLUSION: Electroacupuncture pretreatment could reduce ischemia and reperfusion-induced myocardial injury via possibly increasing the A2b content and regulating the key Ca2+ signaling components, namely inhibiting RyR2 and enhancing P-PLB(S16)/PLB ratio and SERCA2a proteins, so as to diminish the intracellular Ca2+ overload and consequently lessen the myocardial injury.

[Relationship between acupuncture sensations of deqiand different organizational structures of acupoint area].

Acupuncture sensation, as one of the essential signs of deqi (arrival of qi), is closely associated with curative effect. With systematically reviewing the literature regarding relationship between acupuncture sensations of deqi and different organizational structures of acupoint area (skin, connective tissue, muscles, nerves and blood vessels), it is believed that acupuncture sensation of deqi is the product of various organizational structures in acupoint area, which is closely related to the nervous system. The deqi sensations sensed by the hands of acupuncturists, which is called sense of needle stagnation, maybe caused by the contraction of muscles in the acupoint area during the process of needle manipulation. By system review, this paper puts forward a new research idea to explore the role of different manipulations of needling in generating the sense of qi-generating needle based on different acupoint structure and brain function response system, which could provide some reference for clarifying the scientific mechanism and clinical application of acupuncture sensations of deqi.

[Impact of different anesthetic states on acupuncture-mediated modulation of autonomic nervous system in animal studies].

Acupuncture therapy has a positive role in the prevention and treatment of some related diseases by regulating autonomic nervous function. But it has been found in experimental researches that the modulatory effects of acupuncture on autonomic nervous system are not always consistent with each other. Because in the animal studies on the mechanism of acupuncture intervention, the anesthetic agent has to be used and definitely affects the activities of the autonomic nervous system while playing its pharmacological effects. Hence, it is very significant to explore the rational application of anesthetic agents and minimize their unfavorable impacts on the research outcomes. In the present paper, we make a retrospective analysis on (1) the effect of acupuncture intervention on activities of the autonomic nerve in animal models of myocardial ischemia, gastrointestinal mobility, and urinary system; (2) the effect of anesthetics as isoflurane, urethane, pentobarbital sodium, ketamine, α-chloralose, propofolum, etc. on activities of the autonomic nerve system. In terms of different anesthetic modes and various depths of anesthesia by using isoflurane inhalation, mixed solution of urethane and chloralose, etc., some approaches for assessing the state of anesthesia in accordance with the pupillary reflex, righting reflex, footboard reflex, swallowing reflex, heart rate, blood pressure, body temperature, respiration frequency, ventilation volume, oxygen saturation, partial pressure of carbon dioxide, neuromuscular blo-ckade, etc. in combination with the indexes directly and indirectly reflecting functions of the sympathetic and vagus nerves are proposed to analyze the impact of different anesthetic states on the therapeutic effect of acupuncture in various models of dysfunction of the autonomic nerve system. Under the circumstances, it is possible to provide a reference for rational use of anesthetic agents and dosages in the acupuncture research of autonomic nerve regulation.