Biliary Sludge and Pigment Stone Formation in Bile Duct-Ligated Guinea Pigs

We studied the effects of bile stasis in aguinea pig model of pigment gallstone. The common bileducts of guinea pigs were partially ligated, and theguinea pigs killed one or two weeks later. Biliary sludge or stones were examined with the Fouriertransform infrared spectroscopy and the scanningelectromicroscopy. The bile was analyzed for pH, freecalcium, bile acids and bilirubin fractions, and the activities of both bacterial and endogenousbeta-glucuronidase. After bile duct ligation, calciumbilirubinate precipitates or stones formed in all exceptone of the animals studied. The bile pH and the proportion of unconjugated bilirubin rose afterbile duct ligation, with a concomitant fall of bilirubinmonoglucuronide. The activity of bacterialbeta-glucuronidase decreased after ligation, while the activity of endogenous beta-glucuronidase roseat week 2. Our results imply that precipitation ofcalcium bilirubinate in this animal model was induced byan increased bile pH and the nonenzymatic hydrolysis of conjugated bilirubin.     

Can pigment gallstones be induced by biliary stricture and prevented by medicine in Guinea pigs？

AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.     

Lincomycin treatment of guinea pigs causes formation of pigmented phosphate containing gallbladder sludge and stones

We studied the mechanism of gallbladder sludge formation in guinea pigs (n = 30) treated with lincomycin (80 mg/kg/day) for 7 consecutive days. At sacrifice (day 8) gallbladders of treated animals contained turbid bile, sludge and in one animal a single gallstone. The precipitates were amorphous on X-ray diffraction. Infra-red spectroscopy revealed calcium phosphate as the major component. Compared to saline-treated controls (n = 15) concentrations of total protein, total phosphate and total bilirubin in gallbladder bile were significantly increased (P less than 0.05). The increase in total phosphate was due to the inorganic component, since phospholipid phosphorus was unchanged. The relative amounts of unconjugated bilirubin and of bilirubin mono- and diconjugates in gallbladder bile were unaffected by treatment as was beta-glucuronidase activity. However, sludge was enriched in unconjugated bilirubin compared to gallbladder bile. This was most probably caused by alkaline hydrolysis of bilirubin monoconjugates. To some extent, disproportionation of bilirubin monoconjugates in bile or sludge, either in vivo or during sample preparation, might also have led to increased unconjugated pigment.     

Comparison of effects of cholecystokinin and erythromycin on bile chemistry and gallstone formation in aged guinea pigs.

BACKGROUND: There has been considerable interest in gall bladder motility in recent years. We compared the effects of cholecystokinin (CCK) and erythromycin on bile chemistry and gallstone formation in aged guinea pigs. METHODS: Two groups of guinea pigs (1-mo and 3-y old; n=40 each) were studied. Each group was divided into four subgroups of 10 animals each; one subgroup received lithogenic diet, one each received CCK or erythromycin daily in addition to lithogenic diet for 4 weeks, and one received normal diet. After 4 weeks, the presence of gallstones or sludge was recorded and bile composition including concentrations of bile acid, cholesterol, lecithin and protein concentrations was studied. RESULTS: No gallstones were observed in the 1-mo-old animals. In the 3-year-old animals, 9 of 10 guinea pigs on lithogenic diet and 4 of 10 in each treatment subgroup and the normal diet subgroup developed gallstones. CCK and erythromycin had similar effects on bile chemistry and stone formation. CONCLUSIONS: Aging increases the formation of gallstones in guinea pigs. Erythromycin is as effective as CCK in reducing gallstone formation by improving gall bladder motility.     

胆宁片治疗豚鼠胆色素结石的实验研究

[目的]研究胆宁片治疗豚鼠胆色素结石的作用及机制。[方法]构建豚鼠胆色素结石模型,给予胆宁片小、中、大剂量治疗,治疗后观察豚鼠成石率,并用ELISA法测定血清中IL-15、IL-1β及胆汁中IL-15含量。[结果]胆宁片中、大剂量治疗后的豚鼠成石率较模型组下降,差异有统计学意义（P〈0.01）;与模型组比较,胆宁片各剂量组血清中IL-15、IL-1β及胆汁中IL-15含量减少,差异有统计学意义（P〈0.01）,且胆宁片各剂量组间比较差异也有统计学意义（P〈0.01）。[结论]胆宁片能有效治疗豚鼠胆色素结石,其机制与减少IL-15、IL-1β含量有关。     

中药胆宁片治疗胆囊胆固醇结石作用机制的实验研究

[目的]探讨胆宁片对胆固醇结石豚鼠胆汁中黏蛋白及血清IL-2水平的影响.[方法]雌性豚鼠60只,体重（300±20）g,随机分为空白组、模型组、胆宁片组和熊脱氧胆酸组,每组15只;除空白组外,采用“高胆固醇致石食饵诱发法”建立豚鼠胆固醇结石模型,并于造模成功后分别对各治疗组予药物干预,胆宁片组灌服胆宁混悬液0.52 g· kg-1·d-1,熊脱氧胆酸组灌服熊脱氧胆酸混悬液0.05 g·kg-1·d-1,模型组与空白组均灌服等容量的生理盐水,8周后观察各组豚鼠一般情况、胆汁中黏蛋白及血清IL-2水平.[结果]胆宁片可显著降低豚鼠胆固醇结石成石率,并能显著降低胆囊黏蛋白及血清IL-2水平（P＜0.05,P＜0.01）.[结论]胆宁片能直接调节胆囊黏蛋白等相关促成核因子,同时能通过调节血清中IL-2间接调控胆囊黏蛋白水平,从而调控成核过程,对胆囊胆固醇结石有一定的治疗作用.     

Effect of age and sensitivity to cholecystokinin on gallstone formation in the guinea pig

The purpose of this study was to evaluate the effect of age and the role of cholecystokinin therapy on gallstone formation in guinea pigs. Guinea pigs (31 1-mo-old, 31 1-yr-old, and 23 3-yr-old) were placed on a cholelithogenic diet for 2 wk while another 10 guinea pigs of each age group remained on regular chow. Half of each group received a daily injection of cholecystokinin (0.5 nmol/kg). After 2 wk, guinea pigs were killed and the gallbladders were examined for gallstones. The concentrations of bile constituents were determined. The prevalence of gallstones was: 1-mo-old, control 0 out of 16, cholecystokinin 1 out of 15; 1-yr-old, control 3 out of 14, cholecystokinin 5 out of 16; 3-yr-old, control 10 out of 11, cholecystokinin 3 out of 8. Gallstone formation was significantly greater in 3-yr-old controls than in the two younger control groups, and cholecystokinin treatment significantly reduced the incidence of gallstones to near the level seen in younger guinea pigs. In the two younger age groups (but not in the 3-yr-old group), the cholelithogenic diet significantly reduced the concentration of bile salts in bile below that of guinea pigs on a normal diet. The cholelithogenic diet and treatment with cholecystokinin did not alter the relative compositions of bile lipids from that of guinea pigs on a normal diet in any of the three ages studied. In the second experiment we measured gallbladder emptying in response to exogenous infusion of cholecystokinin-8 (100 fmol/kg/h-100 nmol/kg/h) in the same three age groups of guinea pigs in vivo that had been maintained on regular chow. There was no difference in cholecystokinin sensitivity between the two younger age groups, but both were significantly more sensitive to cholecystokinin than the 3-yr-old guinea pigs in rate of gallbladder emptying in the dose range 1 pmol/kg/h-1 nmol/kg/h. We conclude that a major factor in the increased incidence of gallstone formation in the aged guinea pig gallstone model is decreased gallbladder emptying due to decreased gallbladder sensitivity to cholecystokinin.     

The effect of proglumide on gallstone formation in guinea pigs

In this study, the chronic effects of proglumide (PGM, a cholecystokinin/gastrin receptor antagonist) on gallstone formation and hepatic bile secretion were investigated as follows: Group 1: Fed with low protein (14%) lithogenic diet. Group 2: Fed with the same lithogenic diet and was given PGM (250 mg/kg, bid, p. o.). Group 3: Fed with commercial guinea pig chow (protein content 22%). Eight weeks later the animals were operated under urethane anesthesia, the gallbladders were removed and examined for gallstones. Meanwhile, by bile duct cannulation, the hepatic bile flow and bile contents were measured. It was found that: (1) the animal model was valid for the purpose specified; (2) the rate of gallstone formation was significantly lower in PGM group than in the controls (17.5% vs 56.8%, P less than 0.01); and (3) PGM significantly enhanced the flow rates and electrolyte contents and decreased the unconjugated bilirubin content of the hepatic bile. It is concluded that PGM may suppress gallstone formation in guinea pigs on lithogenic diet, and this may be related to its stimulatory effect on hepatic bile secretion and to its ability to induce a decrease in unconjugated bilirubin in the hepatic bile.     

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.     

Influence of fever on biliary elements of guinea pigs

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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.     

Early stages of gallstone formation in guinea pig are associated with decreased biliary sensitivity to cholecystokinin

The purpose of this study was to measure differences in gallbladder sensitivity to cholecystokinin (CCK)in vivo during the early stages of gallstone formation and to correlate these findings to gallbladder CCK receptors. Guinea pigs were placed on either a normal diet or a two-week cholelithogenic diet, after which gallbladder emptying pressure to exogenously administered CCK was measuredin vivo, according to the presence or absence of gallstones. At all doses of CCK tested (except 10^–10 mol/kg), the gallbladder response to CCK of guinea pigs that did not develop gallstones (on the cholelithogenic diet) was more sensitive than that of guinea pigs that did develop gallstones. Neither group was different from guinea pigs on a normal diet. In a second experiment, CCK receptors were measured on gallbladder muscularis from guinea pigs after two weeks on the same diet as in the first experiment. Those guinea pigs that did not develop gallstones had greater concentrations of CCK receptors (149±9 fmol/mg protein) than those that did develop gallstones (70±23 fmol/mg protein). Neither group was different from normal diet guinea pigs (119±57 fmol/mg protein). At the time point measured, there were no differences in the lipid chemistry, or protein concentrations of gallbladder bile between the guinea pigs on the cholelithogenic diet that did or did not develop gallstones, or those on normal guinea pig chow. We conclude that the early stages of gallstone formation in guinea pigs are associated with decreased gallbladder sensitivity to CCK and that this change may be due to a lower concentration of CCK receptors on the gallbladder smooth muscle.Supported by the Wellcome Foundation, Ethicon Foundation, and British Digestive FoundationSupported by grants from the National Institutes of Health (5R37 DK 15241-19, P01 DK 35608, and CA 38657)     

Composition and immunofluorescence studies of biliary "sludge" in patients with cholesterol or mixed gallstones

BACKGROUND/AIMS: Gallbladder bile from patients with cholesterol or mixed gallstones frequently contains biliary "sludge", a suspension of cholesterol monohydrate crystals and pigment granules embedded in mucin and proteins. The composition of biliary "sludge" and the preferential localization of mucin and proteins could be an indicator for its potential role in gallstone formation. METHODS: Ultracentrifugation (100000 g/l h) was used to precipitate "sludge" from bile, and the concentration difference of its main components between native bile and ultracentrifuged bile samples was calculated. After purification of the sediment, immunolocalization was performed for the detection of mucin, IgA, albumin, aminopeptidase, and anionic polypeptide fraction using polyclonal and monoclonal antibodies. RESULTS: The amount of sludge in gallbladder bile was 4.26 mg/ml-0.78 (mean+/-SEM) in patients with cholesterol and 2.51 mg/ml+/-0.39 in patients with mixed stones and cholesterol was the main component (48.9+/-4.6% and 44.4+/-7.1%). The sediment appeared as a mixture of vesicular aggregates and pigment particles which were linked by a gel matrix of mucin containing cholesterol crystals. While anionic polypeptide fraction and aminopeptidase were associated to pigments, IgA was uniformly spread in the crystalline parts of "core-like" structures, and albumin, when it was present, appeared as randomly located small spots. CONCLUSIONS: Our study demonstrates that the cholesterol content and the distribution pattern of mucin and different proteins is similar in the sediments of biliary "sludge" to that previously shown in cholesterol and mixed gallstones. This suggests that biliary "sludge" represents an early stage of gallstone formation in these patients.     

胃动素和血管活性肠肽在不同部位及性质胆石症患者改变的临床研究

目的观察不同部位及性质胆石症患者胃动素(motilin,MTL)和血管活性肠肽(vasoactive intestinal peptide,VIP)含量变化,并探讨肠屏障功能在胆石形成中的作用和意义。方法选取2011年3月-2013年3月就诊于三六三医院且需进行手术治疗的胆结石患者108例,健康对照者20例,按结石部位不同分为4组:健康对照组(A1组,n=20)、胆囊结石组(B1组,n=36)、胆管结石组(C1组,n=36)、胆囊结石合并胆管结石组(D1组,n=36);所有入选患者全部行手术治疗,收集胆石进行化学分析;根据结石不同性质分为健康对照组(A2组,n=20)、胆固醇结石组(B2组,n=40)、胆色素结石组(C2组,n=52)、混合性结石组(D2组,n=16)。分别采用放射免疫分析法测定各组血浆及回肠末端黏膜组织中MTL和VIP的含量。结果不同部位结石患者血浆及肠黏膜组织MTL和VIP的含量变化:B1、C1、D1组与A1组比较差异有统计学意义(P0.05),B1组与C1组比较,C1组与D1组比较,D1组与B1组比较,差异均无统计学意义(P0.05);不同性质结石患者血浆及肠黏膜组织MTL和VIP含量变化B2、C2、D2分别与A2组比较,差异有统计学意义(P0.05),C2组分别与B2、D2组比较差异有统计学意义(P0.05),B2组与D2组比较差异无统计学意义(P0.05)。结论胆色素结石患者存在血浆及肠黏膜组织MTL和VIP含量的改变,胆色素结石形成与肠屏障功能损伤一定的相关性,肠屏障功能损伤可能在促进胆色素结石的形成中发挥一定的作用。     

Gallbladder sludge: a sonographically recognizable stage of lithogenesis

The appearance and the natural course of gallbladder sludge were studied by ultrasonography in 82 patients. Sludge was found in conditions with a functional or organic disturbance of gallbladder emptying: alcoholic cirrhosis and an atonic gallbladder in the fasting state, e.g., extrahepatic ductal obstruction and obstruction of the cystic duct. No clinical complaints could be attributed to sludge. After the normal bile flow had re-established the sludge disappeared in many cases. In 9 of 82 sludge-positive patients (10,9 per cent) ultrasonography revealed gallstone formation. Newly-formed stones obtained from 2 patients had the aspect of pigment stones and were analyzed by infrared spectroscopy. They consisted of calcium bilirubinate. This material constitutes the pigment granules which are suspended in the sludge. It was concluded that sludge was an early phase of stone formation. Alcoholic cirrhosis, obstruction of the biliary tract, gastrectomy, celiac sprue and prolonged fasting may predispose to lithiasis secondary to the precipitation of sludge in a large, atonic or distended gallbladder. Ultrasonography is instrumental to detect an early state of gallstone formation in those patients who carry a risk.     

养肝利胆颗粒对胆色素结石炎症反应环节的影响

[目的]观察养肝利胆颗粒（YGLD）对豚鼠胆色素结石形成过程中炎症环节的影响。[方法]应用雄性豚鼠皮下注射林可霉素联合喂养致石饲料建立胆色素结石模型,观察YGLD对该模型成石率、胆囊容积、胆汁中黏蛋白及C反应蛋白（CRP）浓度的影响。[结果]YGLD组与模型组比较成石率显著降低（P〈0．01）,胆囊容积明显减小（P〈0．05）,胆汁中黏蛋白及CRP浓度明显降低（P〈0．05）。[结论]YGLD通过降低胆汁中黏蛋白、CRP水平来发挥逆转成石胆汁及降低胆色素结石成石率的重要作用。     

The preliminary experimental and clinical study of the relationship between the pigment gallstone and intestinal mucosal barrier

Aims:  To investigate the relations between the formation of pigment gallstone and the function of the intestinal mucosal barrier, as well as the underlying mechanism.
Methods:  Eighty guinea pigs were randomly divided into three groups in which they were respectively given normal diet, gallstone-causing diet, and gallstone-formation diet with a supplementary intestinal mucosal protection compound known as glutamine. The model of pigment gallstone was established after 8 weeks of dietary administration. Indices about the function of the intestinal mucosal barrier and bacterial translocation were measured. Clinical cases were divided into three groups: control, cholesterol gallstone, and pigment gallstone, where the levels of plasma diamine oxidase (DAO), plasma endotoxin and the excretion rates of technetium 99m-diethylene triamine pentaacetic acid (99mTC-DTPA) in the urine of each group were measured.
Results:  In the pigment gallstone group, the level of plasma DAO and endotoxin, the excretory ratio of lactulose and mannitol in urine, the bacterial translocation ratio in the celiac lymph nodes and the activities of β-glucuronidase increased comparing to the control group. The gallstone-formation rate for the intestinal mucosal protection group (GLN) decreased, and other indices, except the activity of β-glucuronidase, were all lower than that of gallstone-formation group. In the clinical experiment, the levels of plasma DAO and endotoxin, as well as the excretory rate of 99mTC-DTPA in urine were higher in the patients with gallstones than that in the control group.
Conclusions:  The formation of pigment gallstone was related to the abnormal function of the intestinal mucosal barrier. The abnormality in the function of the intestinal mucosal barrier probably induced the formation of gallstone by a bacterial translocation mechanism.     

褪黑素对缺血再灌注心律失常的作用

目的:探讨外源性褪黑素(M LT)对在体大鼠心脏缺血再灌注心律失常的作用。方法:34只大鼠随机分为对照组、缺血再灌注(I/R)组及缺血再灌注 褪黑素(I/R M LT)组,I/R组及I/R M LT组在体大鼠心脏左冠状动脉前降支完全阻断10 m in,再灌15 m in,监测记录室性心动过速、室颤的发生情况,并测定局部再灌注心肌中M DA(丙二醛)的含量和SOD(超氧化物歧化酶)的活性。结果:室性心动过速、室颤的发生率I/R M LT组明显低于I/R组(P<0.05);I/R组M DA的含量明显高于对照组及I/R M LT组(P<0.01),SOD活性明显低于对照组及I/R M LT组(P<0.01),I/R M LT组M DA含量及SOD活性与对照组无明显差异(P>0.05)。结论:褪黑素可抑制在体大鼠心脏缺血再灌注心律失常的发生,其作用机制可能与其作为自由基清除剂抗氧化作用有关。     

Effects of sphincter of Oddi motility on the formation of cholesterol gallstones

AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.     

胆胃舒颗粒对胆囊血管活性肠肽受体基因表达的影响

[目的]观察胆胃舒颗粒对胆囊血管活性肠肽(vasoactive intestinal peptide,VIP)受体基因表达的影响及预防胆囊结石的作用.[方法]雄性豚鼠90只,随机分为3组,每组30只,空白组喂养普通饲料40 g/(d·只);模型组喂养胆固醇结石诱石饲料40 g/(d·只);治疗组喂养胆固醇诱石饲料40 g/(d·只),加胆胃舒颗粒溶液1.5ml(含300mg胆胃舒颗粒)灌胃.实验2个月后观察3组胆囊结石情况、胆囊收缩功能及胆囊壁VIP受体基因表达.[结果]胆囊结石形成率:空白组3.33％(1/30),模型组92.59％(25/27),治疗组10.71％(3/28);胆囊收缩功能:空白组胆囊收缩率为(66.83± 5.34)％,模型组(43.06±4.27)％,治疗组(67.93±6.82)％;胆囊壁VIP受体基因表达:空白组0.30±0.07,模型组0.45±0.12,治疗组0.33±0.06.差异均有统计学意义(P＜0.05).[结论]胆胃舒颗粒可降低胆囊结石的形成,其作用机制可能通过降低胆囊壁VIP受体基因表达,从而加强胆囊收缩功能,促使胆汁排泄,防止胆囊结石的发生.