Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in the modulation of electroacupucture (EA) on gastric motility in restrained-cold stressed rats. METHODS: An animal model of gastric motility disorder was established by restrained-cold stress. Gastric myoelectric activities were recorded by electrogastroent erography (EGG). VIP and NO concentrations in plasma and gastric mucosal and bulb tissues were detected by radioimmunoassay (RIA). VIP expression in the gastric walls was assayed using avidin-biotin-peroxidase complex (ABC) and image analysis. RESULTS: In cold restrained stressed rats, EGG was disordered and irregular. The frequency and amplitude of gastric motility were higher than that in control group (P < 0.01). VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously decreased (P < 0.01). Following EA at “Zusanli” (ST36), the frequency and amplitude of gastric motility were obviously lowered (P < 0.01), while the levels of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P < 0.01, P < 0.05) and expression of VIP in antral smooth muscle was elevated significantly (P < 0.01) in comparison with those of model group. CONCLUSION: VIP and NO participate in the modulatory effect of EA on gastric motility. EA at “Zusanli” acupoint (ST36) can improve gastric motility of the stressed rats by increasing the levels of VIP and NO.

Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide,gastrin and cholecystokinin octapeptide

AIM: To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs.

Differences and significance of motilin,vasoactive intestinal peptide and gastrin in blood and gallbladder tissues of patients with gallstones

BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01). CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

Ulcerative colitis(UC)is a chronic relapsed intestinal disease with an increasing incidence around the world.The pathophysiology of UC remains unclear.However,the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot.Vasoactive intestinal peptide(VIP)is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity.It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system.Regulatory B cells(Bregs)are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles.Bregs can regulate immune tolerance by producing interleukin(IL)-10,IL-35,and transforming growth factor-β,suppressing autoimmune diseases or excessive inflammatory responses.The secretion of IL-10 by Bregs induces the development of T helper(Th)0 and Th2 cells.It also induces Th2 cytokines and inhibits Th1 cytokines,thereby inhibiting Th1 cells and the Th1/Th2 balance.With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients,we believe that Bregs can provide a novel strategy for the clinical treatment of UC.Thus,we aim to review the current literature on this evolving topic.

Vasoactive intestinal peptide,a promising agent for myopia?

AIM： To investigate the role of vasoactive intestinal peptide（VIP） in form-deprivation myopia（FDM）.METHODS： FDM was created in three groups of eight chicks by placing a translucent diffuser on their right eyes.Intravitreal injections of saline and VIP were applied once a day into the occluded eyes of groups 2 and 3,respectively.Retinoscopy and axial length（AL） measurements were performed on the first and 8^th days of diffuser wear.The retina mR NA levels of the VIP receptors and the ZENK protein in right eyes of the three groups and left eyes of the first group on day 8 were determined using real time polymerase chain reaction（PCR）.RESULTS： The median final refraction（D） in right eyes were-13.75（-16.00,-12.00）,-11.50（-12.50,-7.50）,and-1.50（-4.75,-0.75） in groups 1,2,and 3,respectively（P〈0.001）.The median AL（mm） in right eyes were 10.65（10.00,11.10）,9.90（9.70,10.00）,and 9.20（9.15,9.25） in groups 1,2,and 3,respectively（P〈0.001）.The median delta-delta cycle threshold（CT） values for the VIP2 receptors were 1.07（0.82,1.43）,1.22（0.98,1.65）,0.29（0.22,0.45） in right eyes of groups 1,2,and 3,and 1.18（0.90,1.37） in left eyes of group 1,respectively（P=0.001）.The median delta-delta CT values for the ZENK protein were 1.07（0.63,5.03）,3.55（2.20,5.55）,undetectable in right eyes of groups 1,2,and 3 and 1.89（0.21,4.73） in left eyes of group 1,respectively（P=0.001）.CONCLUSION： VIP has potential inhibitory effects in the development of FDM.

Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas

AIM： To study the effect of vasoactive intestinal peptide （VIP） on wound healing in experimental alkali burns of the cornea. METHODS： Twenty-seven albino rabbits, weighing 3.2 -0.75 kg were used. Alkali burns were induced on corneas by applying 10 mm Whatman paper No：50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows： 1） control group given no treatment （n=5）; 2） VIP given subconjunctivally （n=6）; 3） VIP injected into anterior chamber （n=6）; 4） NaCI 0.9% given subconjunctivally （n=5）; 5） NaCI 0.9% given into the anterior chamber （n=5）. All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 a.mo to 6 p.m, RESULTS： VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes （PMNL） infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 （P〈0.05）. CONCLUSION： We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenaees and this might prevent the extracellular amorphous substance loss.

Octreotide reverses shock due to vasoactive intestinal peptide-secreting adrenal pheochromocytoma: A case report and review of literature

Vasoactive intestinal peptide-producing tumors （VIP-oma） usually originate in the pancreas and are chara-cterized by diarrhea, hypokalemia, and achlorhydria （WDHA syndrome）. In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, fushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, fushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding;and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confrmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health andwas symptom-free.

Vasoactive intestinal peptide secreting tumour:An overview

Vasoactive intestinal peptide(VIP)secreting tumour(VIPoma)is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells.These present as sporadic,solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year.Only around 5%of VIPomas are associated with multiple endocrine neoplasia type I syndrome.Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhoea,hypokalemia and metabolic acidosis.These coupled with elevated plasma levels of VIP are diagnostic.The majority of VIPomas are malignant and have already metastasized at the time of diagnosis(60%).Metastases occur most frequently in the liver,or regional lymph nodes,lungs,kidneys and bones.Some reports of skin metastases have been documented.Complete surgical resection continues to be the only potentially curative treatment.However,when the neoplasia cannot be excised completely,surgical debulking may provide palliative benefit.Other palliative options have included recently the peptide receptor radionuclide therapy which has shown to be effective and well-tolerated.This article will review all aspects of pancreatic VIPomas highlighting aspects such as clinical presentation,diagnosis and management.

Role of vasoactive intestinal peptide in Aspergillus fumigatus-infected cornea

AIM： To investigate the anti-inflammatory role of vasoactive intestinal peptide（VIP） in Aspergillus fumigatus（A. fumigatus） ketatitis.METHODS： Expression of VIP was tested by polymerase chain reaction（PCR） in C57BL/6 and BALB/c normal and A. fumigatus infected corneas. C57BL/6 mice were pretreated with recombinant（r） VIP, while BALB/c mice were pretreated with VIP antagonist, and then infected with A. fumigatus. Clinical score was recorded. Expression of pro-and anti-inflammatory cytokines, toll-like receptor 4（TLR4）, lectin-like oxidized low-density lipoprotein receptor 1（LOX-1）, and neutrophil infiltration were tested by PCR, enzyme-linked immunosorbent assay（ELISA）, and myeloperoxidase（MPO） assay.RESULTS： VIP mR NA expression in BALB/c cornea was higher than C57BL/6 cornea at 1 and 3 d post infection（p.i.）. rV IP treatment of C57BL/6 mice showed alleviated disease and down-regulated expression of interleukin-1β（IL-1β） and tumor necrosis factor-α（TNF-α）, while IL-10 expression was up-regulated. Neutrophil infiltration and TLR4, IL-17 expression were decreased after rVIP treatment, while LOX-1 expression was up-regulated in C57BL/6. VIP antagonist pretreatment showed increased disease and higher IL-1β, TNF-α, TLR4, IL-17 and MPO levels, while IL-10 and LOX-1 levels were down-regulated in BALB/c mice.CONCLUSION： rVIP alleviate disease response of C57BL/6 mice. VIP antagonist resulted in worsened disease of BALB/c mice. VIP proposed anti-inflammatory role in A. fumigatus keratitis.

Effects of Polygala fallax Hemsl Water Extract on a Mouse Model of Gastric Motility Disorders

[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.

EFFECT OF ERYTHROMYCIN ON GASTRIC DYSMOTILITY AND NEUROENDOCRINE PEPTIDES IN RATS WITH DIABETES MELLITUS

Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin （SS）, vasoactive intestinal peptide （VIP）, motilin （MTL）, and substance P （SP） in plasma and isolated gastric antrum tissue of diabetes mellitus （DM） rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups： control group （n = 10）, DM group （n = 10）, and erythromycin group （DM models with erythromycin treatment, n = 10）. A single dose of streptozotocin （100 mg/kg, dissolved in 0. I mol/L citric acid buffer, pH4.5） was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be （＋＋＋ ） to （＋＋＋＋） over one week were considered successful DM models. The resting tension, mean contractile amplitude and fi＇equency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. Results （1） In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile fi＇equency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension （P 〈 0.01 ）. （2） Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control （P 〈 0.05）, while the SP level decreased （P 〈 0.05）. In the gastric antrum, SS of DM group was significantly higher than that of control group （P 〈 0.01 ）, while SP and MTL levels were lower than those of control group （P 〈 0.05 and P 〈 0.01, respectively）. However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group （P 〈 0.05）. （3） The blood glucose was lower in erythromycin group than DM group （P 〈 0.01 ）. Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

THE AUTOCRINE REGULATORY EFFECT OF VASOACTVE INTESTINAL PEPTIDE ON THE GROWTH OF HUMAN PANCREATIC CARCINOMA CELLS

In the present study, the effects of VIP on the growth of two human pancreatic carcinoma cell lines PU-PAN-l and PANC-I were determined using tritiated thymidine incorporation. VIP receptors. intracellular cAMP and polyamines were investigated. The results indicated that VIP at a concentration of 10-8 mol/L to 10-7 mol/L can significantly stimulate the growth of PU-PAN-I cells but not PANC-1 cells. This effect is dose-dependent and abolished by VIP receptor antagonist, [4-C1-Phe6 . Leu17] VIP, suggesting VIP receptors in PU-PAN-I cells may mediate this effect. VIP can markedly elevate the levels of intracellular cAMP and polyamines in PU-PAN-I cells.indicating that the growth-promoting effect stimulated by VIP may be via a rapid increase in the biosyntheses of cAMP and polyamines. In addition, the VIP-antibody inhibited the growth of PU-PAN-I cells in serum-free culture mediurn. The results above suggested that VIP has an autocrine regulatory effect on this pancreatic carcinoma cell line (PU-PAN-1).

EFFECTS OF ACUPUNCTURE ON IMMUNE RESPONSE RELATED TO OPIOID-LIKE PEPTIDES

Experimental research has recently shown that acupuncture induces the formation of opioid-like peptides (OLPs) in animals. In order to provide further evidence, we tested the beta-endorphin levels and other parameters (VIP, lymphocyte subsets, NK cells and monocyte phagocytosis) in a group of 90 patients suffering from various painful disorders treated with acupuncture. Zusanli (St 36) and Hegu (LI 4) acupoints were selected. A homogeneous group of 30 subjects was used as control. Evaluation of the above parameters was made with 3 series of blood tests before treatment, 30 minutes and 24 hours after acupuncture treatment. In the acupuncture group, the following results were achieved: 1) A considerable increase in beta-endorphin levels remained high even 24 hours after acupuncture treatment. In addition, we demonstrated an inverted correlation between beta-endorphins and VIP; 2) 30 minutes after acupuncture session, 80% of the treated patients showed a significant increase of CD3 and CD4 values and an increase of CD8 24 hours after stimulation; 3) Monocyte phagocytosis was increased in 45% of the treated subjects 30 minutes from starting treatment, and in 100% of them after 24 hours. The percentage of NK cells was also increased in 40% of cases after 30 minutes, and in 50% after 24 hours. However, in the control group, no such significant changes in immune parameters were found.

A study of structure-activity relationship of PACAP

AIMS To investigate the structure-activity relation- ship of PACAP on guinea pig gallbladder by using syn- thetic PACAP/VIP hybrid peptides. METHODS We synthesized the PACAP/VIP hybrid peptides by a simultaneous multiple solid-phase pep- tide synthesizer using the Fmoc strategy. The peptides were tested on the isolated guinea pig gallbladder us- ing an improved horizontal-type organ bath. RESULTS VIP induced relaxation of gallbladder smooth muscle strips,while PACAP27 contracted them. Positions 4,5,9 and 24～26 can be replaced without significant loss in activity. [Leu^(13)]-PACAP27, a substitution in the α-helix domain,also had no signifi- cant loss in activity (P>0.05). It was more potent than [Gly^8]-and [DAsp^8]-PACAP27 and could substi- tute peptides at position 21. Des-[His^1] and [Ala^6]- PACAP27 had no activity at 10^(-7) mol/L. [Gly^8]-, [DAsp^8]-,[Phe^(21)]- and [Pro^(21)]-PACAP27 at 10^(-7)mol/L were about 25% of PACAP27 at 10^(-7) mol/L (P< 0.05). CONCLUSIONS In conclusion,for the physiological action of PACAP in guinea pig gallbladder,the N-termi- nal disordered region is more important than another region.

Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating,qi-replenishing and blood-containing formula

Objective:This study investigated the regulatory effect of non-classical immune parameters on immune thrombocytopenic purpura(ITP)mice by a spleen-invigorating,qi-replenishing and blood-containing formula(SQBF).Method:A total of 80 BALB/c mice were randomly divided into four equal groups(20 mice each):control group,model group,prednisone group and spleen-invigorating,qi-replenishing and blood-containing(SQBF)group.Mice in the model group,prednisone group,and SQBF group were administered anti-platelet serum to induce ITP.The dynamic variations of platelet counts in ITP mice were measured with an automatic blood analyzer before modeling and 48 h,and 8,12 and 15 days following APS injection.Levels of b-endorphin(b-EP),vasoactive intestinal peptide(VIP)and salivary IgA(SIgA)were detected by enzyme-linked immunosorbent assay(ELISA)on 15th day of experiment.Results:SQBF enhanced peripheral blood platelet counts in ITP mice similar to that of prednisone,and both groups showed a statistically significant response compared with the model group(P<.01).The SQBF significantly decreased b-EP levels compared with the model and prednisone intervention groups(P<.05),significantly increased the levels of VIP and SIgA in ITP mice compared with the model group(P<.05)and had significant protective effects on the thymus of ITP mice compared with the model group(P<.01).Conclusions:The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice.Furthermore,it decreased b-EP levels and increased VIP and SIgA,and protected the thymus.This shows that,on base of the brain-gut axis functions,some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses,and also have relationship with the onset of ITP and bleeding and/or hemostasis.It needs further study to determine whether a change in these active factors is related to immediate hemostasis.

Glucocorticoid receptor expression on acute lung injury induced by endotoxin in rats

In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin （LPS） induced shock. Totally 56 SD rats were randomly divided into 4 groups： LPS shock group （n=16）, LPS＋vasoactive intestinal peptide group（VIP） group, （n=16）, LPS＋VIP＋ glucocorticoid （GC） group, （n=16）,and control group （n=8）. LPS shock was induced by intravenous injection of LPS （10 mg/kg） in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP （5 nmol/kg） or VIP and methylprednisolone （3 mg/kg）. The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS＋ VIP group and LPS＋ VIP＋GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group （0.72± 0.24） and LPS＋ VIP group （0.88±0.27） （P〈0.05） as compared with the control group （1.17±0.22）. The LPS shock group showed a more significant down-regualtion than the LPS＋VIP group, but the difference was not statistically significant （P〉0.05）. In contrast, GRmRNA expression in the LPS＋ VIP＋GC group was significantly up-regulated at 6 hours and further at 24 hours （1.45±0.32 and 1.91±0.46 respectively） （P〈0.05）. GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.

The Expression of VIP and SP in the Cochlea of Spontaneously Hypertensive Rats and Its Implication

To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR), and to assess the function of VIP and SP in the cochlea following the damage of hypertension, hearing thresholds of ABR were observed and the fixative (4% paraformaldehyde) was pumped through the circulatory system. Adult Wistar rats (3 months, n=20) served as the control group and SHRs (3 months, n=20) as the hypertension group. Bullas were taken out and cochleas were irrigated in vitro with the same fixative. The number of base turn's spiral ganglions in the sections was counted. The expression of VIP and SP were detected by SABC method and the images of the sections were analyzed. The number of base turn's spiral ganglsons in the hypertension group was significantly less than in the normal group (P<0.01). VIP and SP were expressed in the spiral ganglion cytoplasma and stria vascularis of the two groups. There were no significant difference in the expression of VIP and SP in spiral ganglion cytoplasma (P>0.05) between the two groups. However, in stria vascularis the expression of VIP in the hypertension group was higher than in the normal group (P<0.05), and no significant difference in SP was found between the two groups. It was suggested that VIP not only contributed to the regulation of the cochlea microcirculation, but also made the neurotransmitter in the pathway of the auditory system. However, SP made only the neurotransmitter in the pathway of the auditory system.

Ameliorating Effect and Potential Mechanism of Camellia Oil on Constipated Mice

Constipation is a global epidemic. To evaluate the ameliorating effect of camellia oil on constipation,two slowtransit costive mice models were established by water deprivation or sucralfate gavage. Administration of camellia oil（ 4. 0 and 8. 0 mL/kg/day） significantly shortened the defecation time,increased defecation mass and fecal water content,with efficacies comparable to that of hemp seed oil. Intestinal propulsion test showed that camellia oil significantly enhanced the propelling rates of the charcoal powder in the intestine. Meanwhile,camellia oil also significantly decreased the serum levels of nitric oxide（ NO）,nitric oxide synthase（ NOS） and vasoactive intestinal peptide（ VIP） and increased serum substance P in costive animals. These results suggested that camellia oil can largely relieve slowtransit constipation and enhance the gastrointestinal motility through modulation of serum gastrointestinal motility key factors such as NO,NOS and VIP and substance P.

EFFECT OF ELECTROACUPUNCTURE ON CEREBRAL BLOOD FLOW, VIP AND ET IN RATS WITH VASCULAR DEMENTIA

Objective: To investigate the relationship between electroacupuncture (EA)-induced improvement of regional cerebral blood flow and the alternations of vasoactive intestinal peptide (VIP) and endothelin (ET) in rats with experimental vascular dementia (VD). Methods: 40 Wistar rats were evenly randomized into sham-operation, model, medication (Nimotone) and EA groups. Vascular dementia model was established by repeated cerebral ischemia-reperfusion which was induced by occlusion and reopen of the bilateral common carotid arteries. EA (2～200 Hz, 2～3 mA) was applied to "Baihui"(GV 20), "Dazhui"(GV 14) and "Zusanli"(ST 36) for 30 min, once daily and continuously for 15 days. The regional cerebral blood flow (rCBF) in parietal lobe and hippocampus was determined with method of hydrogen clearance; a step-down avoidance test was adopted to observe the rats’ behavior change; and plasma VIP and ET contents were assayed by radioimmunoassay. Results: In comparison with sham-operation group, the correct rate of step-down avoidance test, rCBF in parietal lobe and hippocampus and plasma VIP level in VD model group lowered significantly (P<0.01) and plasma ET increased considerably (P<0.01). However, compared with model group, the correct rate of step-down avoidance test, rCBF values and plasma VIP in EA group raised obviously while plasma ET declined significantly. No significant differences were found between EA and medication groups in the 4 indexes. Conclusion: EA can raise rCBF in the parietal lobe and hippocampus, elevate plasma VIP level and reduce plasma ET in rats with VD.

Hemostatic mechanism of Jianpi Yiqi Shexue decoction(健脾益气摄血方) in treatment of immune thrombocytopenia

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction(健脾益气摄血方, JYSD) in treating immune thrombocytopathy(ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine(5-HT), β-endorphin(β-EP), vasoactive intestinal peptide(VIP) and compare the changes of blood neurotransmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group(JYSD) combined group(JYSD + Prednisone) control group(Prednisone). The changes of blood neurotransmitter(5-HT, β-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet(PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and β-EP levels were both lower in the ITP group(P < 0.001), and the 5-HT, VIP and β-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group(P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment(P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group(vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set(FAS) and per protocol set(PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study(P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment(P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment(P < 0.05, 0.001). The β-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment(P < 0.05). After treatment, the β-EP levels in the treatment and control groups were significantly lower compared with the combination groups(P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were upregulated, and the differences were statistically significant by rank sum test(P < 0.01), and by t-test(P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of β-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.