GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation.

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41-/-) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41-/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ+ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41-/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41-/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

Origin and stability of pit lake water in Baiyinhua, Inner Mongolia, based on hydrochemistry and stable isotopes.

Isotope technology is widely used in geochemical mechanisms analysis; however, studies on the origin of pit lake water by isotopes in coal concentration areas in grassland are rare. In this study, 20 groups of water samples were collected, which were subjected to chemical analysis to determine the hydrogeochemical characteristics of pit lake water. The mechanisms of pit lake water formation and recharge-evaporation were ascertained through principal component analysis and the Rayleigh fractionation model. The results indicate that the phreatic water is least affected by evaporation, followed by confined water, surface water and pit lake water. The ionic composition of surface water, phreatic water and most of the confined water is mainly affected by leaching, some confined water can be recharged by surface or phreatic water; while the ionic composition of pit lake water is dominantly affected by evaporation (69.4 %) and is less affected by groundwater recharge (17.1 %) and human activities (11.5 %). The pit lake water is recharged by precipitation, phreatic water and the lateral runoff of confined water; however, the proportion of phreatic and confined water recharge is small. The evaporative loss of the pit lake water is 40-61 % of the initial water body.

Effects of continuous intravenous infusion with propofol on intestinal metabolites in rats.

Microbial metabolites play an important role in regulating intestinal homeostasis and immune responses. Propofol is a common anesthetic in clinic, but it is not clear whether it affects intestinal metabolites in rats. Tail vein puncture was performed after adaptive feeding for 1 month in eight 2-month-old rats and they were given continuous intravenous infusion of propofol for 3 h. The feces of rats were divided into different groups based on time periods, with before and after anesthesia with propofol on days 1, 3 and 7 labeled as groups P, A1, A3 and A7, respectively. The effect of continuous intravenous infusion with propofol on rat fecal metabolites was determined using the non-targeted metabolomics technique gas chromatography coupled with a time-of-flight mass spectrometer analysis. The types and contents of metabolites in rat feces were changed after continuous intravenous infusion with propofol, but the changes were not statistically significant. The contents of the metabolites 3-hydroxyphenylacetic acid and palmitic acid increased from day 3 to 7, and it was shown that the two metabolites were positively correlated at a statistically significant level. Linoleic acid decreased to its lowest level on day 3, and it returned to pre-anesthesia level on day 7. At the same time, linoleic acid metabolism was a metabolic pathway that was co-enriched 7 days after infusion with propofol. Spearman correlation analysis showed that there was significant correlation between some differential metabolites and differential microorganisms. It was observed that zymosterol 1, cytosin and elaidic acid were negatively correlated with Alloprevotella in the A3 vs. P group. In the A7 vs. P group, cortexolone 3 and coprostan-3-one were positively correlated with Faecalibacterium, whilst aconitic acid was negatively correlated with it. In conclusion, the present study revealed statistically insignificant effects of continuous intravenous propofol on the intestinal metabolites in rats.

GPR109a Regulates Phenotypic and Functional Alterations in Macrophages and the Progression of Type 1 Diabetes.

SCOPE: Dietary fibers can alter gut microbiota and microbial metabolite profiles. SCFAs are produced by bacterial fermentation of fiber, mediating immune homeostasis through G-protein-coupled receptors (GPCRs). GPR109a, a receptor for niacin and butyrate, expressed by immune cells and non-immune cells, is a key factor regulating immune responses. However, the role and underlying mechanisms of GPR109a in type 1 diabetes (T1D) remain unclear. METHODS AND RESULTS: Experimental T1D was induced by streptozotocin in GPR109a-deficient (Gpr109a-/- ) and wild type mice. The study found that Gpr109a-/- mice were more susceptible to T1D with dysregulated immune responses, along with increased M1 macrophage polarization (from 10.55% to 21.48%). Further, an adoptive transfer experiment demonstrated that GPR109a-deficient macrophages promoted the homing of intestine-derived type 1 cytotoxic T cells to pancreas (from 18.91% to 24.24%), thus disturbing the pancreatic immune homeostasis in non-obese diabetic mice. Mechanistically, GPR109a deficiency promoted M1 macrophage polarization associated with the activation of suppressor of cytokine signaling 3-signal transducer and activator of transcription 1 signaling pathway. CONCLUSION: The findings reveal that macrophage GPR109a deficiency accelerates the development of T1D. Activation of GPR109a on macrophage by dietary components may provide a new strategy for preventing or treating T1D.

Preoperative intestinal microbiome and metabolome in elderly patients with delayed neurocognitive recovery.

BACKGROUND: Delayed neurocognitive recovery (dNCR) is a common complication of the central nervous system in elderly patients. Currently, it is not clear whether the occurrence of dNCR is associated with the intestinal microbiota and its related metabolites. This study investigated the preoperative intestinal microflora and faecal metabolites of dNCR patients. METHODS: Twenty-two elderly urological patients were divided into a dNCR group (D group) and a non-dNCR group (ND group) according to the postoperative Mini-Mental State Examination (MMSE) score on the first and third day after surgery. A postoperative MMSE score ≤ 2 points compared with the preoperative score was considered evidence of dNCR. We used a comprehensive method that combined 16S rRNA gene sequencing and untargeted metabolomics to study the preoperative intestinal microflora and faecal metabolites of the two groups, and conducted correlation analysis between them. RESULTS: Compared with the D group, the microbial community in the ND group was more abundant. At the family level, the ND group was significantly enriched in Lachnospiraceae, Peptostreptococcaceae and Muribaculaceae. At the genus level, the faecal microbiota of the ND group was differentially enriched in Agathobacter, Dorea, Fusicatenibacter, Coprococcus_2 and Romboutsia while that of the D group was differentially enriched in Anaerofilum. Untargeted metabolomics revealed significant differences in eight different metabolites between the two groups, including ribose, ethanol, leucine, maltose, pentadecanoic acid, malonic acid 1,3,4-dihydroxybenzoic acid and 3-hydroxypalmitic acid. In addition, differential metabolites were associated with the abundance of specific bacteria. CONCLUSIONS: The occurrence of dNCR may be associated with the intestinal flora and its related metabolite composition of patients before surgery.

Effects of Electroacupuncture on Gastrointestinal Motility Function, Pain, and Inflammation via Transient Receptor Potential Vanilloid 1 in a Rat Model after Colonic Anastomoses.

Background: Complications after colon surgery are a major obstacle to postoperative recovery. The purpose of this study was to investigate the effect of electroacupuncture (EA) at Zusanli (ST36) on gastrointestinal motility in rats after colonic anastomosis and the mechanism of transient receptor potential vanillin 1 (TRPV1) channel in regulating gastrointestinal motility, pain, and inflammation. Methods: The rats were randomly divided into six groups, including the control, model, EA, sham-EA, capsaicin, and capsaicin+EA groups, with preoperative capsaicin pretreatment and EA treatment at ST36 acupoint after surgery. Rats were treated using EA at ST36 or sham acupoints after surgery for 5 days. Capsaicin was intraperitoneally injected into rats 3 hours before surgery. Gastrointestinal motility was assessed by measuring the gastric residue, small intestinal propulsion in vivo, contractile tension, and frequency of isolated muscle strips in vitro. The mechanical withdrawal threshold (MWT) of abdominal incision skin and spontaneous nociceptive scores were observed and recorded in rats after colon anastomosis. The expressions of TRPV1, substance P (SP), neurokinin 1 (NK1) receptor, nuclear factor kappa-B (NF-κB), interleukin- (IL-) 6, L-1ß, and tumor necrosis factor- (TNF-) α were determined. Results: Compared with the model group, electroacupuncture at ST36 point could significantly reduce the residual rate of stomach in rats after operation and increase the propulsive force of the small intestine and the contraction tension of the isolated smooth muscle. Electroacupuncture also increased postoperative day 3 MWT values and decreased postoperative spontaneous nociception scores. In addition, electroacupuncture treatment downregulated the expressions of IL-6, IL-1ß, TNF-α, TRPV1, NF-κB, SP, and NK1 receptors in the colon tissue of rats after colonic anastomosis. Conclusions: Our study showed that electroacupuncture at ST36 acupoint could improve gastrointestinal motility in rats after colonic anastomosis and relieve intestinal inflammation and pain. The mechanism may be to inhibit the activation of NF-κB and SP/NK1 receptor signaling pathways by inhibiting TRPV1.

Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice.

In recent years, more and more attention has been paid to intestinal microbiome. Almost all operations will go through the anesthesia process, but it is not clear whether the intervention of anesthesia alone will affect the change in the intestinal microbiome. The purpose of this study was to verify the effect of sevoflurane inhalation anesthesia on the intestinal microbiome. The animal in the experimental group was used to provide sevoflurane inhalation anesthesia for 4 hours. The control group was not intervened. The feces of the experimental group and the control group were collected on the 1st, 3rd, 7th and 14th days after anesthesia. Sevoflurane inhalation anesthesia will cause changes in the intestinal microbiome of mice. It appears on the 1st day after anesthesia and is most obvious on the 7th day. The specific manifestation is that the abundance of microbiome and the diversity of the microbiome is reduced. At the same time, Untargeted metabonomics showed that compared with the control group, the experimental group had more increased metabolites related to the different microbiome, among which 5-methylthioadenosine was related to the central nervous system. Subsequently, the intestinal microbiome diversity of mice showed a trend of recovery on the 14th day. At the genus level, the fecal samples obtained on the 14th day after anesthesia exhibited significantly increased abundances of Bacteroides, Alloprevotella, and Akkermansia and significantly decreased abundances of Lactobacillus compared with the samples obtained on the 1st day after anesthesia. However, the abundance of differential bacteria did not recover with the changing trend of diversity. Therefore, we believe that sevoflurane inhalation anesthesia is associated with changes in the internal microbiome and metabolites, and this change may be completed through the brain-gut axis, while sevoflurane inhalation anesthesia may change the intestinal microbiome for as long as 14 days or longer.

Effects of continuous intravenous infusion of propofol on intestinal flora in rats.

Under normal circumstances, the gut microbiota, host, and external environment establish a dynamic ecological balance and maintain human health. Once this balance is broken, the intestinal flora dysregulation will form, manifested by changes in the diversity, richness, proportion, location and biological characteristics of the gut microbiota. The hypothesis that propofol alters gut microbes was tested in a rat model with continuous intravenous infusion of propofol. Eight male wistar rats underwent tail vein puncture and catheterization respectively, and were continuously pumped with propofol for 3 h. Feces were collected from each rat before and on the 1 st, 3rd, 7th and 14th days after intervention. Finally, the effect of continuous intravenous infusion of propofol on the intestinal flora of rats was analyzed by high-throughput 16S rRNA gene amplification sequencing. Through high-throughput 16S rRNA gene amplicon sequencing analysis, we found that continuous intravenous infusion of propofol had little effect on intestinal flora in rats. Analysis of Alpha (shannon diversity index) showed that group A-7 was different from group P and group A-1 (P = 0.034), and recovered on the 14th day. Although the species diversity analysis showed a significant difference among the five groups (P = 0.049), the distribution of most fecal samples in the PCoA showed a clustered distribution, indicating similarity. In addition, no significant difference was found in the statistical KEGG difference pathway through LEfSe analysis.

Effects of immunotherapy on mortality in neonates with suspected or proven sepsis: a systematic review and network meta-analysis.

BACKGROUND: To investigate the efficacies of different immunotherapies in neonates with suspected or proven sepsis. METHODS: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2019 that investigated different immunotherapies in neonates with suspected or proven sepsis. Comparisons were among immunotherapies and between immunotherapy and placebo. The review was registered in the PROSPERO CRD database. RESULTS: All-cause mortality was not significantly different between patients who received the immunoglobulin (IgG), IgM-enriched immunoglobulin (IgGAM), granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) immunotherapies and those who received placebo. The RRs of the immunotherapies were 0.80 (95% CI: 0.57 to 1.1), 0.45 (95% CI: 0.17 to 1.0), 0.93 (95% CI: 0.64 to 1.2) and 0.67 (95% CI: 0.39 to 1.1), respectively. Compared with placebo, none of the interventions showed statistically significant differences in the duration of hospital stay. The MDs of the immunotherapies were - 2.7 (95% CI: - 8.4 to 3.5), - 0.18 (95% CI: - 7.3 to 7.7), - 1.7 (95% CI: - 7.3 to 3.9) and - 7.2 (95% CI: - 28 to 13), respectively. CONCLUSIONS: No significant differences in all-cause mortality or the duration of hospital stay were found in neonates with suspected or proven sepsis treated with the four types of immunotherapies and those treated with placebo.

The cardioprotective effect of dexmedetomidine on regional ischemia/reperfusion injury in type 2 diabetic rat hearts.

BACKGROUND: Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist commonly used during perioperative periods due to its sedation and analgesia effect. It is confirmed that DEX has cardioprotective effects against ischemia/reperfusion (I/R) injury. We investigated whether DEX administration is beneficial to type 2 diabetic rats subjected to I/R injury. METHODS: The diabetes model was established by providing a high-fat diet for 2 weeks followed by injecting 35 mg/kg streptozotocin (STZ). The myocardial I/R model consisted of left anterior descending coronary artery occlusion for 30 min followed by reperfusion for two-hours. DEX was administered before ischemia; alternatively, yohimbine was administered with or without DEX before ischemia. At the end of reperfusion, the rats were sacrificed, and hearts were isolated for histology. The levels of glycogen synthase kinase-3ß (GSK-3ß) and phosphorylated GSK-3ß (p-GSK-3ß) were quantitatively analyzed. The infarct size was measured via Evans Blue and 2,3,5­triphenyltetrazolium chloride (TTC) staining. Plasma samples were collected to measure the levels of cardiac Troponin T (cTnT). Arrhythmia scores were recorded during the first few minutes of reperfusion. RESULTS: DEX preconditioning significantly reduced myocardial infarct size, arrhythmia scores and the plasma cTnT levels, and increased the p-GSK-3ß levels. All of these protective effects of DEX were reversed by co-administration of yohimbine. CONCLUSIONS: These results suggested that DEX preconditioning exerted a cardioprotective effect against regional I/R injury in diabetic rats.

Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain.

Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine­induced antinociception and tolerance in cancer pain is unclear. Therefore, we investigated the effects of coadministration of a CB2 receptor agonist AM1241 and morphine on TRPV1 expression and tolerance in cancer pain. Coadministration of AM1241 and morphine for 8 days significantly reduced morphine tolerance, as assessed by measuring paw withdrawal latency to a radiant heat stimulation, in Walker 256 tumor­bearing rats. Repeated morphine treatment for a period of 8 days induced upregulation of the TRPV1 protein expression levels in the DRG in the tumor­bearing rats, although no change in mRNA expression. Pretreatment with AM1241 reduced this morphine­induced upregulation of TRPV1 and the effect was reversed by the CB2 receptor antagonist AM630. Our findings suggest that coadministration of a CB2 receptor agonist AM1241 and morphine reduced morphine tolerance possibly through regulation of TRPV1 protein expression in the DRG in cancer pain.

Mechanical ventilation modes for respiratory distress syndrome in infants: a systematic review and network meta-analysis.

INTRODUCTION: The effects of different mechanical ventilation (MV) modes on mortality outcome in infants with respiratory distress syndrome (RDS) are not well known. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published through April 2014 that assessed mortality in infants with RDS given different MV modes. We assessed studies for eligibility, extracted data, and subsequently pooled the data. A Bayesian fixed-effects model was used to combine direct comparisons with indirect evidence. We also performed sensitivity analyses and rankings of the competing treatment modes. RESULTS: In total, 20 randomized controlled trials were included for the network meta-analysis, which consisted of 2,832 patients who received one of 16 ventilation modes. Compared with synchronized intermittent mandatory ventilation (SIMV) + pressure support ventilation (PSV), time-cycled pressure-limited ventilation (TCPL) (hazard ratio (HR) 0.290; 95% confidence interval (CI) 0.071 to 0.972), high-frequency oscillatory ventilation (HFOV) (HR 0.294; 95% CI 0.080 to 0.852), SIMV + volume-guarantee (VG) (HR 0.122; 95% CI 0.014 to 0.858), and volume-controlled (V-C) (HR 0.139; 95% CI 0.024 to 0.677) ventilation modes are associated with lower mortality. The combined results of available ventilation modes were not significantly different in regard to the incidences of patent ductus arteriosus and intraventricular hemorrhage. CONCLUSION: Compared with the SIMV + PSV ventilation mode, the TCPL, HFOV, SIMV + VG, and V-C ventilation modes are associated with lower mortality.

Electroacupuncture at ST36 accelerates the recovery of gastrointestinal motility after colorectal surgery: a randomised controlled trial.

OBJECTIVES: To evaluate whether electroacupuncture (EA) at ST36 can accelerate the recovery of gastrointestinal motility after colorectal surgery. METHODS: Forty patients of American Society of Anesthesiologists physical status II and III undergoing elective open resection of malignant colorectal tumours were included in this study. Using a sealed envelope method, the patients were randomly divided into two groups either receiving EA (EA group) or sham EA (SEA group). Data regarding the recovery of bowel function (times to the first bowel sounds, passage of flatus and defaecation) were collected and analysed. RESULTS: In the EA group, the time intervals from surgery to the first bowel movement and passage of flatus were shorter than in the SEA group (13±10 h vs 19±13 h, p<0.05 and 23±14 h vs 32±18 h, p<0.05, respectively). There was no significant difference between the groups regarding the time to first defaecation (68±45 h vs 72±53 h, p>0.05). CONCLUSIONS: EA at ST36 accelerates the recovery of gastrointestinal motility after colorectal surgery. TRIAL REGISTRATION: JJ22011-15.

Hybrid organic-inorganic monolithic enzymatic reactor with SBA-15 nanoparticles incorporated.

A novel enzymatic reactor was prepared by incorporating SBA-15 nanoparticles into hybrid organic-inorganic monolith and immobilizing trypsin with glutaraldehyde as bridging reagent. Preparation and operation conditions including nanoparticles percentage and residence time were optimized to improve the digestion efficiency. The digestion products were characterized by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) with sequence coverage of 50%, 93% and 71% for bovine serum albumin, myoglobin and cytochrome C, while consuming only about 19s in dynamic mode. Compared with enzymatic reactor without nanoparticles incorporated, the enzymatic reactor with SBA-15 nanoparticles embedded achieved higher digestion efficiency by introducing more trypsin, which was originated from combination of SBA-15 nanoparticles and hybrid organic-inorganic monolith.

The effects of electroacupuncture at the ST36 (Zusanli) acupoint on cancer pain and transient receptor potential vanilloid subfamily 1 expression in Walker 256 tumor-bearing rats.

BACKGROUND: Several studies have addressed the expression of transient receptor potential vanilloid subfamily 1(TRPV1) playing an important role in the generation of cancer pain. Electroacupuncture (EA) is an effective method of acupuncture shown to attenuate different kinds of pain such as inflammatory, neuropathic, and cancer. In this study, we investigated the effect of EA on cancer pain caused by intraplantar injection of Walker 256 carcinoma cells and cancer-driven TRPV1 expression in the dorsal root ganglions (DRGs). METHODS: Rats were randomly divided into 4 groups: the nontumor cell inoculation group (normal control, n = 8); Walker 256 carcinoma cell inoculation group (tumor control, n = 8); sham point electrical stimulation treatment with Walker 256 carcinoma cell inoculation group (SES, n = 8); EA treatment with Walker 256 carcinoma cell inoculation group (EA, n = 8). The time courses of thermal, mechanical sensitivity, and spontaneous nocifensive behavior were determined. In addition, TRPV1 expression in DRGs was observed by quantitative real-time polymerase chain reaction and Western blotting. RESULTS: Injection of cancer cells decreased the paw withdrawal threshold, increased spontaneous nocifensive behavior, and induced significant thermal hyperalgesia that was attenuated by EA at the ST36 acupoint (2 Hz, 0.3 ms, ≤1 mA). TRPV1 mRNA and protein in DRGs were upregulated in the cancer pain model, and EA at ST36 acupoint counteracted the cancer-driven upregulation of TRPV1 expression in the corresponding DRGs. CONCLUSIONS: EA at ST36 could attenuate cancer-induced pain, at least in part, through suppressing TRPV1 mRNA and protein upregulation in the DRGs.

Lack of preemptive analgesia by intravenous flurbiprofen in thyroid gland surgery: a randomized, double-blind and placebo-controlled clinical trial.

BACKGROUND: Nowadays, increasingly more preemptive analgesia studies focus on postoperative pain; however, the impact of preemptive analgesia on perioperative opioid requirement is not well defined. This study was carried out in order to evaluate whether preoperative intravenous flurbiprofen axetil can reduce perioperative opioid consumption and provide postoperative analgesia in patients undergoing thyroid gland surgery. METHODS: Ninety patients undergoing elective thyroid gland surgery were randomly assigned to three groups. Group A (Control) was administered Intralipid(®) 2 ml as a placebo 15 min before the cervical plexus block and at the end of the surgery; Group B (Routine analgesia) was administered a placebo 15 min before the cervical plexus block and flurbiprofen 50 mg at the end of the surgery; Group C (Preemptive analgesia) was administered intravenous flurbiprofen 50 mg 15 min before the cervical plexus block and a placebo at the end of the surgery. Sufentanil administration during the surgery and the 24 h satisfaction score on analgesic therapy were both recorded. The analgesic efficacy was assessed at 1, 2, 4, 6, 8, 12, and 24 hours after the surgery, based on visual analog scales. RESULTS: Ninety patients were involved in the study. One patient from Group B did not have their scheduled surgery; eighty-nine patients completed the study. There were no significant differences in the patient demographics between the three groups. Visual analog scales: 1, 2, 4 h for Group A was significantly higher than Groups B and C (P<0.05); Sufentanil administration during surgery: Group C was obviously lower compared to Groups A and B (P<0.05); 24 h satisfaction score: Groups B and C were higher than Group A (P<0.05). CONCLUSION: Preoperative administration of intravenous Flurbiprofen axetil reduced analgesic consumption during surgery, but not postoperative pain scores.

The effects of electroacupuncture on TH1/TH2 cytokine mRNA expression and mitogen-activated protein kinase signaling pathways in the splenic T cells of traumatized rats.

BACKGROUND: Surgical trauma contributes to postoperative immune suppression, which is associated with an increased susceptibility to subsequent infections. Electroacupuncture (EA) can alleviate pain and exert immunoregulatory effects. However, the mechanism underlying the immnuomodulation effects of EA is not fully elucidated. Therefore, we investigated the effects of EA on T helper (Th)1/Th2 cytokine production and mRNA expression and evaluated the signaling regulatory mechanism of EA effects. METHODS: Rats were divided into four groups (n = 24 each): control, trauma, trauma (T) + sham EA, and T + EA. EA was applied to Zusanli (ST36) and Lanwei (Extra37) acupoints at 20 min after surgery for 30 min, and then performed once a day on postoperative days 1-5. Splenic T cells were isolated and the production and mRNA expression of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 were assayed. The activation of mitogen-activated protein kinase and the DNA binding activity of nuclear factor (NF)-kappaB and activator protein (AP)-1 were examined. RESULTS: Paw withdrawal threshold and paw withdrawal latency were significantly increased in the T + EA group compared with the trauma group from postoperative day 1 (paw withdrawal threshold: 5.8 +/- 0.7 vs 3.0 +/- 0.7 g; paw withdrawal latency: 7.0 +/- 0.8 vs 4.5 +/- 0.5 s; P < 0.001) to day 5 (9.0 +/- 0.6 vs 5.5 +/- 0.6 g; 12.0 +/- 1.3 vs 7.0 +/- 0.8 s; P < 0.001). Th1 cytokine (IL-2 and interferon-gamma) production and mRNA expression in splenic T cells of traumatized rats were significantly decreased on postoperative day 3 (P < 0.001, trauma group versus control group), whereas Th2 cytokine (IL-4 and IL-10) production and mRNA expression were increased (P < 0.001). This was accompanied with a significant depression in the activity of extracellular-regulated protein kinase (ERK)1/2, p38, NF-kappaB, and AP-1 (P < 0.001, trauma group versus control group). EA administration increased Th1 cytokine protein and mRNA expression, suppressed Th2 cytokine protein and mRNA expression (P < 0.05, T + EA group versus trauma group), and increased the activity of ERK1/2, p38, NF-kappaB, and AP-1 (P < 0.001, T + EA group versus trauma group). CONCLUSIONS: EA regulates a balance between Th1 and Th2 cytokines at protein and mRNA levels in splenic T cells, and, at least in part, involves the signaling pathways of ERK1/2, p38, NF-kappaB, and AP-1. The findings suggest that EA may improve immune suppression after surgical trauma.