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.METHODS:Thirty-four adult male Hartley guinea pigs were divided randomly into two groups:the control group and pigment stone group.The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice,and were fed a pigment lithogenic diet and sacrificed after 3,6,9 and 12wk.SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage.Serum vasoactive intestinal peptide(VIP),gastrin and cholecystokinin octapeptide (CCK-8)were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay.RESULTS:The incidence of pigment gallstone formation was 0%,0%,16.7%and 66.7%in the 3-,6-,9-and 12-wk group,respectively.The frequency of myoelectric activity decreased in the 3-wk group.The amplitude of myoelectric activity had a tendency to decrease but not significantly.The frequency of the SO decreased significantly in the 9-wk group.The SO basal pressure and common bile duct pressure increased in the 12-wk group(25.19±7.77 mmHg vs 40.56±11.81 mmHg,22.35±7.60 mmHg vs 38.51±11.57mmHg,P<0.05).Serum VIP was significantly elevated in the 6-and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group.CONCLUSION:Pigment gallstone-causing diet may induce SO dysfunction.The tension of the SO increased.The disturbance in SO motility may play a role in pigment gallstone formation,and changes in serum VIP and CCK-8 may be important causes of SO dysfunction.     

Albiflorin Granule significantly decreased the cholesterol gallstone formation by the regulation of insulin transduction signal

Objective:To study the mechanism of insulin resistance in the cholesterol gallstone formation from insulin signal transduction pathway so as to reveal the possible mechanism and the effective role of Albiflorin Granule on preventing the cholesterol gallstones.Methods:Serum triglycerides(TG),free fatty acid(FFA),and total cholesterol(TC) from different groups were measured and liver cells Ins R,PKB,IKK-β protein expression levels were detected by western blotting.Results:Albiflorin significantly decreased the cholesterol gallstone formation rate,increased glucose infusion rate in gallstone guinea pigs and improved insulin resistance.Compared with the normal group,insulin receptor and PKB protein expression in GS group were significantly reduced.IKK-β protein in the GS group increased significantly and Albiflorin could reduce IKK-β protein expression in guinea pig liver cells.Conclusions:The model of insulin resistance in cholesterol gallstone guinea pig was successfully established,which plays an important role in the cholesterol gallstone formation.All aspects of insulin signaling pathway are involved in gallstone formation.Albiflorin can regulate various aspects of insulin signal transduction pathway to prevent the formation of gallbladder.     

Role of nucleation of bile liquid crystal in gallstone formation

AIM: To explore the role of bile liquid crystal in the process of gallbladder stone formation and to provide bases for preventing and treating cholelithiasis.METHODS: 46 guinea pigs, half males and half females,were randomly divided into control group and stone-causing group. Normal feed and stoneleading feed were used respectively to raise guinea pigs in the control group and stone-causing group. The guinea pigs were killed in three batches during the raising period. Under polarizing microscope, the pattern changes of bile liquid crystal in the gallbladder biles of the guinea pigs in the control group and stone-causing group were dynamicly observed respectively in single-blind trial.RESULTS: It was found that there were few crystals in the guinea pigs‘ biles of the control group, and their Malta cross was small and scattered, and existed in single form. With the increase of the feeding days, bile liquid crystals grew and Malta cross became bigger with their distribution densified, denser somewhere, but always existed in single form. While those of the stone-causing group had more bile liquid crystals, Malta cross was big and merged in strings.With the increase of the feeding days, bile liquid crystals grew in amount and strings of Malta cross increased and became bigger. The crosses in strings were arranged more and more regularly and they gradually changed into stone crystals.CONCLUSION: Formation of gallbladder stone is a process of nudeation from different substances, and the causing-stone gallbladder bile is a constantly supersaturated solution, and bile liquid crystal is a nucleation factor in the formation of gallbladder stones. The process of nucleation includes gathering, merging and phase-changing of bile liquid crystals.The process of gathering, merging of bile liquid crystal is the key to nucleation.     

Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoeiectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postchole cystectomy syndrome.     

Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig model

BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstoneforming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliaryβ-glucuronidase were assessed after 8 weeks. RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77±43×106 EU/L to 1367±525×l06 EU/L, P<0.01) and increased activity of biliaryβ-glucuronidase (endogenousβ-glucuromdase from 122.1±39.5 to 209.8±47.5 Fishman Unit, P<0.01, and exogenous p-glucuronidase from 573.5±476.9 to 2206.6±983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except P-glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliaryβ-glucuronidase.     

Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones

Background:Cholesterol gallstones account for over 80% of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3 a,MUC3 b,MUC4,MUC5 ac and MUC5 b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20 ± 1.50 vs.109.40 ± 3.84 HU,P 0.0 0 01).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3 a,MUC3 b,MUC5 ac and MUC5 b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49 ± 0.69 vs.10.23 ± 0.54 ng/m L,P 0.05),in the body(14.54 ± 0.94 vs.11.87 ± 0.85 ng/m L,P 0.05) as well as in the neck(14.77 ± 1.04 vs.10.85 ± 0.72 ng/m L,P 0.05) of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r = 0.569,P 0.05) in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.     

Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

AIM:To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues. METHODS:Eight Baa mini-pigs were used in this study. Experimental models with common bile duct (CB ) defect (0.5-1.0 cm segment of CB resected) were established and then CB was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co- (1,2-propanediol)]. In addition, a vascularized greater omentum was placed around the stent and both ends of CB . Cholangiography via gall bladder was per-formed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture. Complete blood count was examined pre-and post-operatively to estimate the inflammatory reaction. Liverenzymes and serum bilirubin were examined pre-and post-operatively to evaluate the liver function. Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis. The other three pigs were raised for one year for long-term observation. RESULTS:All the animals underwent surgery successfully. There was no intraoperative mortality and no bile leakage during the observation period. The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation, the difference was not statistically significant (P = 0.652). The plasma level of alanine aminotrans-ferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P = 0.810). Nevertheless, the plasma level of γ-glutamyl transferase was increased after operation in both groups (P = 0.004), especially 2 wk after operation. The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P = 0.227), so did the serum direct bilirubin (P = 0.759). By cholangiography via gall bladder, we found that the stent maintained its integrity of shape and was still in situ at month 1, and it disap-peared completely at month 3. No severe CB dilation and stricture were observed at both months 1 and 3. No pig died during the 3-mo postoperative observation period. No sign of necrosis, bile duct stricture, bile leakage or abdominal abscess was found at reoperation at month 3 postoperatively. Pigs had neither fragments of stent nor stones formed in the CB . Collagen deposit was observed in the anastomosis by hematoxylin and eosin (HE) and asson's trichrome stains. No severe cholestasis was observed in liver parenchyma by HE staining. Intestinal obstruction was found in a pig 4 mo after operation, and no bile leakage, bile duct stricture or biliary obstruction were observed in laparotomy. No sign of bile duct stricture or bile leakage was observed in the other two pigs. CONCLUSION:The novel method for repairing bileduct defect yielded a good short-term effect without postoperative bile duct stricture. However, the longterm effect should be further studied.     

Ultrastructural view of colon anastomosis under propolis effect by transmission electron microscopy

AIM： To evaluate the effect of propolis administration on the healing of colon anastomosis with light and transmission electron microscopes. METHODS： Forty-eight Wistar-AIbino female rats were divided into two groups and had colon resection and anastomosis. In group Ⅰ, rats were fed with standard rat chow pre- and postoperatively. The rats in group Ⅱ were fed with standard rat chow and began receiving oral supplementation of propolis 100 mg/kg per day beginning 7 d before the operation and continued until they were sacrificed. Rats were sacrificed 1, 3, 7 and 14 d after operation, and anastomotic bursting pressures measured. After the resection of anastomotic segments, histopathological examination was performed with light and transmission electron microscopes by two blinded histologists and photographed. RESULTS： The colonic bursting pressures of the propolis group were statistically significantly better than the control group. UItrastructural histopathological analysis of the colon anastomosis revealed that propotis accelerated the phases of the healing process and stimulated mature granulation tissue formation and collagen synthesis of fibroblasts. CONCLUSION： Bursting pressure measurements and ultra structural histopathological evaluation showed that administration of propolis accelerated the healing of colon anastomosis following surgical excision.     

Gallbladder bile composition in patients with Crohn＇s disease

AIM:To further elucidate the pathogenesis andmechanisms of the high risk of gallstone formation inCrohn's disease.METHODS:Gallbladder bile was obtained from patientswith Crohn's disease who were admitted for electivesurgery (17 with ileal/ileocolonic disease and 7 withCrohn's colitis).Fourteen gallstone patients servedas controls.Duodenal bile was obtained from tenhealthy subjects before and after the treatment withursodeoxycholic acid.Bile was analyzed for biliary lipids,bile acids,bilirubin,crystals,and crystal detection time(CDT).Cholesterol saturation index was calculated.RESULTS:The biliary concentration of bilirubin wasabout 50% higher in patients with Crohn's disease thanin patients with cholesterol gallstones.Ten of the patientswith Crohn's disease involving ileum and three of thosewith Crohn's colitis had cholesterol saturated bile.Fourpatients with ileal disease and one of those with colonicdisease displayed cholesterol crystals in their bile.About1/3 of the patients with Crohn's disease had a shortCDT.Treatment of healthy subjects with ursodeoxycholicacid did not increase the concentration of bilirubin induodenal bile.Several patients with Crohn's disease,with or without ileal resection/disease had gallbladderbile supersaturated with cholesterol and short CDT andcontained cholesterol crystals.The biliary concentrationof bilirubin was also increased in patients with Crohn'scolitis probably not due to bile acid malabsorption.CONCLUSION:Several factors may be of importance forthe high risk of developing gallstones of both cholesteroland pigment types in patients with Crohn's disease.     

An Experimental Study on the Flexibility of Prevention against Thrombosis Following Mechanical Valve Replacement by tPA Gene Transduction

Objectives Use a gene suture immersed recombinant tissue-type plasminogen activator （r-tPA）expression plasmid to transduce myocardia to prevent the thrombosis after mechanical tricuspid valve replacement in pigs. Methods A r-tPA gene plasmid was constructed and conjugated to a novel cationic phosphonolipid and a r-tPA gene suture was made. Eighteen pigs were selected and divided into two groups at randomization. There were 9 pigs in the experimental group and 9 in the control group, all the 18 pigs＇ tricuspids were replaced with mechanical valves. The gene threads were sutured into the right ventricular walls near mechanical valves and an ultrasound was used on the surfaces of the right ventricular walls for the gene transfer in the experimental group. Coagulative function, D-dimer level of the blood and the thrombosis on the surfaces of the valves were observed. Results r-tPA gene plasmid was successfully constructed and r-tPA protein was expressed in the ventricular cells around the gene sutures. D-dimer reached its peak level （ 1.67 ±0. 79） μg · mL^-1 in 1 week after operation in two groups, but it decreased to preoperation level thereafter in control group and kept on the high level and reincreased to a new high level （ 1.89 ± 0.79 ） μg · mL^-1 until the end of the experiment in experimental group. The thromboses around the valves were found in all the control group （100%） but only 1 （ 11.11% ） case in experimental group. There were no changes in prothrombin time pre and post operation in two groups. Conclusions Using gene suture immersed r-tPA expression plasmid to transduce myocardia might be a best substitution for life long anti-coagulation therapy for the patients, who underwent operation.     

Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation

AIM： To investigate the possibilities and advantages of laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation.METHODS： Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct. The hospitalization time, hospitalization costs, operation time, operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS： The operation time and post-operative liver functions of the two groups of patients had no significant differences, while the hospitalization time, hospitalization costs and operative complications of the laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION： For patients with gallstones in the left lobe of liver and in the common bile duct, laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time, reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation. This kind of operation has more advantages than traditional open operation.     

Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation

AIM: To investigate the possibilities and advantages of laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation.METHODS: Laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct. The hospitalization time, hospitalization costs, operation time, operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS: The operation time and post-operative liver functions of the two groups of patients had no significant differences, while the hospitalization time, hospitalization costs and operative complications of the laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION: For patients with gallstones in the left lobe of liver and in the common bile duct, laparoscopic hepatic left lateral lobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time, reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation. This kind of operation has more advantages than traditional open operation.     

Relationship between intraduodenal peri-ampullary diverticulum and biliary disease in 178 patients undergoing ERCP

BACKGROUND:The presence of intraduodenal peri-ampullary diverticulum is often observed during upper digestive tract barium meal studies and endoscopic retrograde cholangiopancreatography(ERCP).A few papers in China and overseas reported that the diverticulum had something to do with the incidence of cholelithiasis. This study was undertaken to further test this notion and ascertain the relationship between intraduodenal peri- ampullary diverticulum and biliary disease,especially the formation of bile duct pigment stones. METHODS:A total of 178 patients who had undergone ERCP or endoscopic sphincterotomy(EST)were studied retrospectively.They were divided into 6 groups according to the category of biliary disease,and the incidence rates of intraduodenal peri-ampullary diverticulum were calculated. RESULTS:There were 44 patients with intraduodenal peri- ampullary diverticulum in 81 patients with primary bile duct pigment stones(54.32%),4 in 8 patients with bile duct stones and gallbladder stones(50%),7 in 33 patients with bile duct stones secondary to gallbladder stones(21.21%), 3 in 21 patients with inflammation and stricture of the end of the bile duct and papilla(14.29%),1 in 22 patients with carcinoma of the end of the bile duct and papilla(4.54%), and 5 in 13 patients with post-cholecystectomy syndrome or sphincter of Oddi dysfunction(38.46%). CONCLUSIONS:The incidence rate of intraduodenal peri- ampullary diverticulum in patients with primary bileduct pigment stones is higher than that in patients with bile duct stones secondary to gallbladder stones,patients with inflammation and stricture of the end of the bile duct and papilla,and patients with carcinoma of the end of the bile duct and papilla.These findings indicate that the anatomical abnormalities and malfunction of the sphincter of Oddi play an important role in the formation of bile duct pigment stones.     

Role of interleukin-6/signal transduction and activator of transcription 3 signalling in cholic acid-induced intestinal carcinogenesis in Apc~(min/+) mice

正Objective To investigate the effect of cholic acid on intestinal carcinogenesis and its possible mechanisms in Apcmin/+mice.Methods Twenty Apc~(min/+) mice were divided into control group and cholic acid group,10 mice in each group.The mice of control group were fed with regular diet,and the mice of cholic and group were fed with regular diet and 0.4%cholic acid.All mice were     

INVESTIGATION ON MODEL OF INFLAMMATORY PLEURAL EFFUSION IN GUINEA PIGS

Objective To establish an animal model of inflammatory pleural effusion.Methods Forty guinea pigs were divided into two groups: experimental group with 7 subgroups and control group. In the experimental group the right chest cavity of each guinea pig was injected with 0.8～1.0 ml of 1% carrageenan, and guinea pigs of each subgroup were killed and observed respectively on day 1, 2, 3, 5, 7, 10 and day 14 after injection.Results Occurring on day 1(within 24 hours), pleural effusion reached the maximum on day 2～3 after injection, so did the neutrophil count in pleural effusion and inflammation of both pleura and lungs and then gradually decreased. The fibrosis and adhesion of pleura appeared on day 7 and were obvious on day 10. The encysted pleurisy was formed on day 14.Conclusion The carrageenan is an ideal pleural inflammatory inducer. This animal model is useful for studying pleural effusion.     

Surgical anatomy of innervation of the gallbladder in humans and Suncus murinus with special reference to morphological understanding of gallstone formation after gastrectomy

AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.
METHODS： The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers （n = 10）. Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus （S. murinus） was examined employing whole mount immunohistochemistry.
RESULTS： Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.
CONCLUSION： The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.     

Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement

AIM: To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca2+, and on the gastric emptying and the intestinal propulsive activity in mice. METHODS: Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension. The effects of magnolol 10-3,10-4,10-5 mol/L, and honokiol 10-4, 10-5,10-6 mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine (Ach) and 5-hydroxvtryptamine (5-HT) was assessed respectively. The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol (0.5, 2, 20 mg/kg) on gastric emptying and intestinal propulsion. RESULTS: Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCI2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca2+-free medium and extracellular Ca2+-dependent contraction induced by Ach. Each group of magnolol and honokiol experiments significantly decreased the residual rate of nuclein in the stomach and increased the intestinal propulsive ratio in mice. CONCLUSION: The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.     

Mechanism of benign biliary stricture： A morphological and immunohistochemical study

AIM: To explore the mechanism of benign biliary stricture. METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on day 3, in wk 1, 3 and mo 3, 6 after operation. CD68, TGF-β1 and α-SMA were examined by immunohistochemical staining, respectively. RESULTS: The mucosal epithelium of the bile duct was slowly recovered, chronic inflammation lasted for a long time, fibroblasts proliferated actively, extracellular matrix was over-deposited. Myofibroblasts functioned actively and lasted through the whole process. The expression of macrophages in lamina propria under mucosa, TGF-β1 in granulation tissue, fibroblasts and endothelial cells of blood vessels, oc-SMA in myofiroblasts were rather strong from the 1st wk to the 6th mo after operation. CONCLUSION: The type of healing occurring in bile duct belongs to overhealing. Myofibroblasts are the main cause for scar contracture and stricture of bile duct. High expressions of CD68, TGF-β1 and a-SMA are closely related to the active proliferation of fibroblasts, extracellular matrix over-deposition and scar contracture of bile duct.     

Effect of emodin on mobility signal transduction system of gallbladder smooth muscle in Guinea pig with cholelithiasis

Objective: To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus. Methods: The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone(GS) group, emodin group and ursodesoxycholic acid(UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups of induced models by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin(CCK) and [Ca~(2+)]i were analyzed successively by radioimmunoassay and flow cytometry. The protein and mR NA of Gsα, Giα and Cap in cholecyst cells were determined by western blotting and real time polymerase chain reaction(RT-PCR). Results: Emodin or UA can relieve pathogenic changes in epithelial cells and muscle cells in gallbladder of guinea pig with cholesterol calculus by microscope and transmission electron microscope. In the cholecyst cells of GS group, CCK levels in plasma and [Ca~(2+)]i decreased, the protein and m RNA of GS group were downregulated,the protein and m RNA of Gi and Cap were up-regulated. Emodin significantly decreased the formative rate of gallstone, improved the pathogenic change in epithelial cells and muscle cells, increased CCK levels in plasma and [Ca~(2+)]i in cholecyst cells, enhanced the protein and mR NA of Gs in cholecyst cells, reduced the protein and mR NA of Gi and Cap in cholecyst cells in guinea pig with cholesterol calculus. Conclusion: The dysfunction of gallbladder contraction gives rise to the disorders of mobility signal transduction system in cholecyst smooth muscle cells, including low content of plasma CCK and [Ca~(2+)]i in cholecyst cells, abnormal protein and mRNA of Gs, Gi and Cap. Emodin can enhance the contractibility of gallbladder and alleviate cholestasis by regulating plasma CCK levels, [Ca2+]i in cholecyst cells and the protein and mR NA of Gs, Gi and Cap.     

Rabeprazole is effective for bile reflux oesophagitis after total gastrectomy in a rat model

AIM:To elucidate the effect of a proton pump inhibitor(PPI,rabeparazole)on oesophageal bile reflux in oesophagitis after total gastrectomy.METHODS:Twenty-one 8-week-old male Wistar rats were studied.They were performed oesophagoduodenostomy of total gastrectomy to induce oesophageal reflux of biliary and pancreatic juice.Five rats were performed the sham operation(Sham).On post-operative day 7,they were treated with saline(Control)(n=8)or PPI(rabeprazole,30 mg/kg per day,ip)(n=8)for 2 wk.On post-operative 21,all rats were sacrificed and each oesophagus was evaluated histologically.Oesophageal injury was evaluated by macroscopic and microscopic findings as well as the expression of cyclooxygenase-2(COX2).We measured bile acid in the oesophageal lumen and the common bile duct.RESULTS:At 3 wk after surgery,a histological study analysis revealed an increase in the thickness of the epithelium,elongation of the lamina propria and basal cell hyperplasia in the oesophageal mucosa.The macroscopic ulcer score and microscopic ulcer length of the control group were significantly higher compared to those of the rabeprazole-treated group.The expression of COX2 was significantly increased according to the immunostaining in the control group compared to rabeprazole-treated group.Although there was no difference between the control and PPI groups in the total bile acid in the common bile duct,the bileacid activity in the oesophageal lumen was significantly decreased in the rabeprazole-treated group due to augmentation of the duodenal motor complex.CONCLUSION:With this model,rabeprazole is good effect for reflux esophagitis after total gastrectomy from bile reflux.Bile acid is an important factor in the mucosal lesion induced by duodenal reflux.