Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22

BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.

Effects of sleeve gastrectomy plus trunk vagotomy compared with sleeve gastrectomy on glucose metabolism in diabetic rats

AIM To investigate the effects of sleeve gastrectomy plus trunk vagotomy(SGTV) compared with sleeve gastrectomy(SG) in a diabetic rat model.METHODS SGTV, SG, TV and Sham operations were performed on rats with diabetes induced by high-fat diet and streptozotocin. Body weight, food intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance(HOMA-IR), hepatic insulin signaling(IR, IRS1, IRS2, PI3 K and AKT), oral glucose stimulatedinsulin secretion, GLP-1 and ghrelin were compared at various postoperative times.RESULTS Both SG and SGTV resulted in better glucose tolerance, lower HOMA-IR, up-regulated hepatic insulin signaling, higher levels of oral glucose-stimulated insulin secretion, higher postprandial GLP-1 and lower fasting ghrelin levels than the TV and Sham groups. No significant differences were observed between the SG and SGTV groups. In addition, no significant differences were found between the TV and Sham groups in terms of glucose tolerance, HOMA-IR, hepatic insulin signaling, oral glucose-stimulated insulin secretion, postprandial GLP-1 and fasting ghrelin levels. No differences in body weight and food intake were noted between the four groups.CONCLUSION SGTV is feasible for diabetes control and is independent of weight loss. However, SGTV did not result in a better improvement in diabetes than SG alone.

Subdiaphragmatic vagotomy reduces intake of sweet-tasting solutions in rats

Studies have shown that there are strong interactions between gustatory and visceral sensations the central nervous system when rats ingest sweet foods or solutions. To investigate the role of th subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats depriv~ of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water II E

Studies on histological features and motor functions of gastric antrum after high selective vagotomy associated with mucosal

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Surgical Management of Perforated Peptic Ulcer;Closure with Omental Patch versus Definitive Repair with Vagotomy and Gastrojejunostomy: A Comparative Study

Background: The perforation of peptic ulcer is a common and serious life threatening surgical emergency. Up-till now no consensus was reached regarding the best practice in management of perforated peptic ulcer. The aim of this study is to evaluate and compare between both management strategies of perforated peptic ulcer;performing simple closure of the perforation with an omental patch then H. pylori eradication and inhibition of acid secretion using long time proton pump inhibitors versus performing definitive repair of perforated peptic ulcer (closure of the perforation with an omental patch, truncal vagotomy and gastrojejunostomy to discover a proper management strategy of perforated peptic ulcer. Patients and Methods: In the current study we included 30 patients which were divided into 2 groups: group 1 included 15 patients where we managed them by simple closure of the perforation with an omental patch then H. pylori eradication and inhibition of acid secretion using long time proton pump inhibitors and group 2 included 15 patients where we performed closure of the perforation with an omental patch, truncal vagotomy and gastrojejunostomy. Results: We found that younger patient underwent vagotomy and gastro-jejunostomy technique (p Conclusions: Peptic ulcer perforation could be safely managed by primary closure and covering by omentum in addition to medical treatment of H. pylori infection and inhibition of acid secretion especially in old patients with comorbid condition who presented late or with shock.

Comparative study on highly selective vagotomy and its combination with mucosal antrectomy in treatment of duodenal ulcer

Objective:To comparethe therapeuticeffectsof highly selectivevagotomyand mucosalantrectomy(HSV-MA)withthosesingleHSVon48casesof duodenalulcerinorderto confirmthatHSVcouldnotresultinhyper-gastrinemiaandulcerrecurrence.Methods:Forty-eightpatientswithduodenalulcerwerecarefullyexamined.Randomly,28of themwereoperatedon withHSV-MAand20withsimpleHSV.Postoperatively,thelevelof gastricacid,serumgas-trinandthepositiverateof helicobacter pylori(Hp)weredetermined.Results:It was foundthatthelevelof gastricacid was significantlylowerin thepostoperativeperiodsof theHSV-MAandsimpleHSVgroupsthanin thepreoperative stage;thelevelof serumgastrinwassignificantlylowerintheHSVgroupthanintheHSV-MAgrouppostoperativelyand thanin thepreoperativestage.Thepositiverateof Hpinfectionwas markedreducedin theHSV-MAgroupthanin the casesof preoperativestage.Conclusion:On thebasisof theabovementionedfindings,itis consideredthatHSV-MA wouldnotresulttheoccurrenceof ulcerrecurrenceandsuggestedthatHSV-MAis a betterapproachto treatchronicduo-denalulcer.

Effect of Vagotomy on Acute Pancreatitis in Rats

One hundred and eighty two SD rats were randomly divided into the normal control group, fast operating group and food intake operating group. The experimental model of acute pancreatitis (AP) in rats was established by injecting 5 % sodium taurocholate into the pancreatic duct of rat according to Aho's method. The sandostatin was used for positive contrast. The concentrations of serum amylase, calcium, C reaction protein (CRP) and interleukin 6 (IL 6) were assayed respectively at different time points. The pathological sections were observed. Each operating group contained 10 rats. The mortality of the operating groups was observed during the 24 h. The serum amylase level in the AP rats was reduced after receiving vagotomy (VG, P <0.05). Although the serum calcium level in most groups was decreased, the reduction in the group with VG plus sandostatin was not obvious ( P >0.05). The increase of CRP and IL 6 was not obvious after VG ( P >0.05). The change of mortality was not significant ( P >0.05). The pathological sections showed that the AP pathological change was mild after VG. The disease condition of food intake operating group was more serious than that of fast operating group. It was suggested that VG had some influence on the prognosis of AP in rats.

Functional Roux-en-Y Gastric Bypass (F-RYGB), with Preservation of Duodenal Access: Report of Two Revisional Cases of Sleeve Gastrectomy

Objective: This case report aimed to demonstrate a possible neuromuscular effect of Latarjet nerves transection or truncal vagotomy, in association with sleeve gastrectomy plus antrojejunostomy, in order to reproduce a Roux-en-Y gastric bypass (RYGB) mechanistic principles, in patients with previous Sleeve Gastrectomy (SG) who had had weight regain, with or without concomitant gastroesophageal reflux disease (GERD). Background: Sleeve gastrectomy (SG) is one of the most frequently performed bariatric operations worldwide. Nevertheless, weight regain and gastroesophageal reflux disease (GERD) have been consistently demonstrated, in association with this technique, which may require a revisional procedure. RYGB is an option in such a situation but, implies in gastrointestinal exclusions, which represents a shortcoming of this revision. Surpassing this inconvenient would be of great value for the patients. Methods: We describe herein two cases of SG revision for weight regain and GERD, with a follow-up of one year. Gastroesophageal reflux disease was evaluated by validated questionnaire, upper endoscopy, seriography, high resolution manometry (HRM) and impedance pHmetry (I-pHmetry), in the pre and postoperative periods. A re-Sleeve Gastrectomy with antrojejunal anastomosis was done in both cases, after informed consents. The Latarjet nerves were transected in one case, due to a bleeding in the left gastric vessels and a truncal vagotomy was required in the other, to appropriately treat an associated hiatal hernia. Results: In the postoperative evaluation it was observed a pyloric spasm in both cases, during seriography and endoscopy, kept until the one-year follow-up. There was unidirectional contrast flow to the gastrointestinal anastomosis, filling the jejunal limb, in radiologic contrast study. No contrast passed through the pylorus. Nonetheless, the duodenum was kept endoscopically accessible. In the one-year evaluation, weight loss was adequate and GERD resolution was obtained in both cases, confirmed by endoscopic and functional esophageal assessment, together with symptoms questionnaire. Conclusion: The association of Latarjet nerves sectioning or truncal vagotomy with re-sleeve gastrectomy plus gastrointestinal anastomosis (antrojejunal), in a revision for a failed sleeve, can represent a technical approach, to reproduce RYGB results, without exclusions and with duodenum endoscopic accessibility maintenance. It maybe could be applied for primary surgeries. Additional studies are necessary to confirm this hypothesis.

DNA Content in Pancreatic ExocrinalCells after Vagotom yand Electron Microscopy in Rats

Fifty six SD rats were randomly divided into the normal control group and the operation group. The operating group was subdivided into six groups on the basis of killing time (the 12th h, the first day, 3rd day, first week, 2nd week and 4th week) after vagotomy (VG). The pancreatic tissues were taken for HE and Feulgen staining. The DNA content of pancreatic exocrine cells was determined by a domestically fabricated computer image analyzing system. In the control group, on the first day or in the first week after VG, the pancreatic samples were taken for transmission electron microscopic examination. The DNA content of pancreatic exocrinal cells was decreased from 1 to 3 days after VG. The secretion was found to be in inhibitory state and One week later, it gradually restored. The results indicated that the proliferation and the function of the SD rat's pancreatic exocrinal cells were prohibited at initial stage after VG, which might be concerned, at least in part, with dominance and nutrition of vagus.

The Long Magenstrasse with pyloroplasty as functional gastric bypass: 6-years experience, 308 operations

Background: The Long Magenstrasse with py-loroplasty as functional Gastric Bypass (briefly LMGBP) procedure for morbid obesity may re- duce the incidence of side effects associated with gastric restrictive and malabsorptive sur- gery, particularly on quality of life and long-term nutritional insufficiency. In follow-up to pre- liminary findings in 34 patients, we report the results of an additional 274 LMGBPs performed over the past 3 years. Methods: Between October 2003 and 2009, 308 patients were treated with the LMGBP. 149 patients underwent open procedures;74, hand-assisted laparoscopic surgery (HALS);and 85 were operated laparo-scopically. 17% had ≥ 125 mg/dl glycemia, 43% sleep apnea, 38% hyperlipidemia, 12% hyperuricemia, and 58% arterial hypertension under treatment. Results: The mean BMI of 256 pre-operatively normoglycemic patients at 1 year was 29 (range 26-31);27 (25-30) in 45 patients at 3 years;and 27.5 (26-30) in 12 patients at 5 years. Mean BMI of 53 preoperatively hyperglycemic patients (≥ 125 mg/dl) at 1 year (21 patients) was 32 (29-34), and at 3 years (9 patients), 32.5 (30- 33). 15 patients with preoperative type 2 diabetes under oral treatment required no therapy 3-6 months after surgery. Patients reported considerable appetite reduction with rapid satiety but maintained good nutrition with no supplementation. There was no mortality. Conclusions: Safe and effective sustained weight loss, positive metabolic changes, and appetite diminution with rapid satiety were seen after LMGBP.

Hippocampal plasticity after a vagus nerve injury in the rat

Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine （BrdU） incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus, leading to alteration of neurogenesis.

Effects and mechanisms of L-glutamate microinjected into nucleus ambiguus on gastric motility in rats

Background L-glutamate （L-GLU） is a major neurotransmitter in the nucleus ambiguus （NA）, which can modulate respiration, arterial pressure, heart rate, etc. This study investigated the effects and mechanisms of L-GLU microinjected into NA on gastric motility in rats. Methods A latex balloon connected with a pressure transducer was inserted into the pylorus through the forestomach for continuous recording of the gastric motility. The total amplitude, total duration, and motility index of gastric contraction waves within 5 minutes before microinjection and after microinjection were measured. Results L-GLU （5 nmol, 10 nmol and 20 nmol in 50 nl normal saline （PS） respectively） microinjected into the right NA significantly inhibited gastric motility, while microinjection of physiological saline at the same position and the same volume did not change the gastric motility. The inhibitory effect was blocked by D-2-amino-5-phophonovalerate （D-AP5, 5 nmol, in 50 nl PS）, the specific N-methyI-D-aspartic acid （NMDA） receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-（1H,4H）-dione （CNQX） （5 nmol, in 50 nl PS）, the non-NMDA ionotropic receptor antagonist. Bilateral subdiaphragmatic vagotomy abolished the inhibitory effect by microinjection of L-GLU into NA. Conclusions Microinjection of L-GLU into NA inhibits the gastric motility through specific NMDA receptor activity, not non-NMDA receptor activity, and the efferent pathway is the vagal nerves.

Effect of oxytocin on gastric ischemia-reperfusion injury in rats

The effect of peripherally administered oxytocin(OT)on gastric ischemia-reperfusion injury(GI-RI)and its possible mechanism were investigated.The Sprague-Dawley(SD)rats were randomly divided into different treatment groups(n=6).The animal GI-RI model was established by clamping the celiac artery for 30 min to induce ischemia and then released to allow reperfusion for 1 h,and the degree of GI-RI was assessed by scoring the gastric mucosal damage index(GMDI),the gastric fluid output,gastric fluid output,gastric acidity were measured and the surgical preparations of vagotomy and sympathectomy were used to investigate the possible mechanism of OT on GI-RI.The results were as follows.Compared with the control group(NS plus GI-R only,GMDI 121.33P10.40,n=6),the intra peritoneal(ip)administration of oxytocin(20,100μg/0.5 mL)obviously attenuated GI-RI(P<0.05),GMDI were 82.33P14.26,53.5P5.58 respectively(n=6);the gastric fluid output and the gastric acidity(evaluated by pH)of the control group were(430.17P87.36)μL,1.55P0.25(n=6),and those of the OT group were(102.45P48.00)μL,2.65P0.40(n=6)res pectively;differences had statistical significance(P<0.01).The effect of oxytocin was reversed by atosiban,a selective oxytocin receptor antagonist.The GMDI of the group given atosiban 10 min before OT was 138.17P24.06(n=6),which had no significant difference with the control group.Oxytocin further attenuated GI-RI after vagotomy and sympathectomy(GMDI 6.83P8.89,29.67P5.54,n=6),compared with the GI-R group and the oxytocin group(P<0.01).These results indicated that the oxytocin could significantly protect gastric mucosal against injury induced by ischemia-reperfusion,and the oxytocin receptor was involved.This effect of oxytocin may be mediated through the vagus and sympathetic nerve,and then lead to the reduction of gastric juice output and the depression of gastric acidity.