Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones

Increased synthesis of prostaglandins in the wall of the gallbladder may play a role in the pathogenesis of cholesterol gallstones by mediating mucus hypersecretion and thereby accelerating nucleation and the precipitation of cholesterol-supersaturated bile. We induced gallstones in prairie dogs and guinea pigs by feeding a cholesterol-supplemented diet for periods as long as 6 weeks. Gallbladder prostaglandin synthesis was quantitated by specific radioimmunoassays that measured the amount of various prostanoids released from the gallbladder during in vitro incubation. The gallbladders of cholesterol-fed prairie dogs showed increased synthesis of prostaglandin E2, prostaglandin F2a, and thromboxane and increased concentrations of glycoprotein in gallbladder bile. These changes were evident as early as 2 weeks after institution of the cholesterol diet, although cholesterol gallstones did not form until 4 or more weeks. In contrast, cholesterol feeding of the guinea pig did not induce cholesterol supersaturation. In this species pigment gallstones formed, probably as a result of a cholesterol-induced hemolytic anemia, and gallbladder mucus hypersecretion did not occur. Pigment gallstone formation in the guinea pig was associated with an increase in prostacyclin synthesis, but the synthesis of prostaglandin F2a and thromboxane was decreased. Increased prostaglandin synthesis may contribute to the formation of cholesterol gallstones but does not appear to participate in pigment gallstone formation.     

Gallstone formation in dogs after selective occlusion of the portal vein branches

The effects of selective portal blood interruption on gallstone formation were investigated experimentally in dogs. The gallstone incidence in group I (left portal vein occlusion, N = 10) was 60 per cent at 1 month after the ligation, 64 per cent at 2 months (N = 9) and 88 per cent at 3 months (N = 8), whereas the incidence in group II (right portal vein occlusion, N = 5) was 0 per cent at 1 and 2 months (N = 5) after the ligation and 20 per cent at 3 months (N = 5). All canine gallstones, which were similar to human black stones on morphological and infrared spectroscopic examination, formed only in the gallbladders of both groups. Bile analysis showed that cholesterol, phospholipids and total bile acid concentrations in the gallbladder bile were significantly decreased in group I after the ligation. Microscopy of the gallbladders in group I showed prominent PAS-positive material in the gallbladders. Gallstone formation after portal vein occlusion is thought to depend on the extent of the area of portal blood interruption.     

Nonobese diabetic mice have diminished gallbladder motility and shortened crystal observation time

Diabetes and obesity are strongly associated and are risk factors for cholesterol gallstone disease. Leptinde ficient and leptin-resistant diabetic obese mice have enlarged, hypomotile gallbladders. In addition, bile from gallbladders of leptin-deficient mice has enhanced cholesterol crystal formation, whereas bile from gallbladders of leptin-resistant mice has delayed crystal observation time. To determine the effect of diabetes alone, we hypothesized that leptin-normal, nonobese diabetic (NOD) mice would have reduced biliary motility and rapid crystal formation. Twenty control and 9 prediabetic and 11 diabetic NOD, 12- to 26-week-old mice underwent glucose measurement and cholecystectomy for muscle bath stimulation with neurotransmitters. An additional group of 200 control and 78 NOD 12-week-old mice underwent microscopic bile examination for cholesterol crystal formation. Compared with control mice, prediabetic NOD mice had similar glucose levels and gallbladder volumes. Diabetic NOD mice had higher sugar levels and larger gallbladder volumes (P < 0.001) than control mice. Prediabetic NOD gallbladders had less contractility (P < 0.01) than control gallbladders, and contractility worsened (P < 0.01) in diabeticNODmice.NODmice formed cholesterol crystals earlier than did control mice (P<0.05). Nonobese diabetic NOD mice have (1) decreased gallbladder contraction to neurotransmitters, which worsens with development of diabetes, and (2) rapid crystal formation. We conclude that diabetes alone alters gallbladder motility and cholesterol crystal formation. Presented at Digestive Disease Week, 2004 SSAT Plenary Session, and Residents’ Conference, New Orleans, Louisiana, May 15–21, 2004 (oral presentation). This work was supported by National Institutes of Health grant R01-DK44279.     

The role of cystic duct resistance in the pathogenesis of cholesterol gallstones

Several recent clinical and laboratory observations suggest that impaired gallbladder emptying is important in the pathogenesis of cholesterol cholelithiasis. However, the exact mechanism by which gallbladder stasis occurs in the majority of patients who form gallstones has not been clear. We tested the hypothesis that impaired gallbladder emptying antedates cholelithiasis and results from increased resistance to bile flow. Using the prairie dog gallstone model, resistance to flow through the cystic duct (CD) and sphincter of Oddi (SO) was measured in control and cholesterol-fed animals. Prairie dogs were fed either a control (trace cholesterol) or a 0.4% cholesterol-enriched diet known to induce gallstones in 6 weeks. Resistance across the CD and SO was measured at 4 weeks (pregallstone) and 16 weeks (gallstone). Resistance was measured by infusing lactated Ringer's solution through the CD and SO at four separate flow rates while gallbladder and distal common bile duct pressures were recorded. Resistance to flow through the cystic duct increased prior to gallstone formation and continued to increase during the 16 weeks of cholesterol feeding. In comparison, sphincter of Oddi resistance remained normal despite chronic exposure to lithogenic bile and formation of stones within the gallbladder. The increased cystic duct resistance observed prior to gallstone formation provides a mechanism for diminished gallbladder emptying and suggests an etiological role for increased cystic duct resistance in the pathogenesis of cholesterol gallstones.     

The rotary gallstone lithotrite to aid gallbladder extraction in laparoscopic cholecystectomy

During laparoscopic cholecystectomy, a large stone burden may cause difficulty when extracting the gallbladder through the abdominal wall. Currently, the alternatives available to the surgeon include increasing the incision, removing stones singly, or utilizing complex fragmentation techniques like the pulsed dye laser. We have employed an electromechanical rotary gallstone lithotrite (RGL) to fragment stones to an aspiratable size. Initially, cholesterol spheres were pulverized in a latex balloon to demonstrate the efficacy of the device. Then, human gallstones were placed in the balloon and reduced to fragments less than or equal to 1 mm from initial sizes of 4-24 mm. Human stones were then inserted in ex vivo porcine gallbladders in a controlled experiment and treated with the device. Ten out of 12 tests were completed within 30 s; one test required 49 s and one 105 s to achieve complete fragmentation. Blinded histological evaluation demonstrated that tissue abrasion caused by use of the device would not interfere with the diagnosis of unsuspected malignancy. Clinical trials have now commenced under the auspices of the hospital ethical committee.     

单个与多发胆固醇结石患者胆道细菌感染状况及与免疫球蛋白相关性的对照研究

目的 多发胆固醇结石患者胆囊炎症程度较高,可能与结石形成有关.对多发和单个胆固醇结石患者胆道细菌感染状况及与免疫球蛋白含量的相关性进行对照研究.方法 :用半定量PCR法测定分析38例胆囊结石患者胆石、胆汁和粘膜的细菌DNA阳性率和菌落数,并测定相应胆汁和粘膜IgA、IgG、IgM含量.结果 :单个和多发胆石组的胆汁细菌DNA阳性率分别为75.0%和73.7%,胆囊粘膜细菌DNA阳性率分别为66.7%和64.0%,结石核心的细菌DNA阳性率分别为57.1%和85.7%,结石外周细菌阳性率分别为71.4%和85.7%,两组间差异均无显著性.两组间胆汁和粘膜IgA、IgG、IgM含量差异无显著性,菌落数与免疫球蛋白含量不相关.多发胆石组粘膜细菌DNA阳性者的胆囊粘膜IgA、IgG含量高于阴性者(P<0.05).单个和多发胆石组胆汁胆固醇饱和指数(CSI)差异无显著性,各组内胆汁细菌阳性与阴性者的CSI差异也无显著性.结论 :多发和单个胆固醇结石患者胆囊细菌感染率相似,细菌感染不是多发胆固醇结石患者胆囊炎症严重的原因.多发胆固醇结石患者胆囊粘膜细菌与IgA、IgG含量增高有关,可能间接参与胆固醇结石的形成过程.     

Er:YAG laser ablation of prairie dog gallbladder epithelium for the prevention of gallstones

We hypothesized that laser ablation of gallbladder epithelium would prevent gallstone formation in prairie dogs. An Er:YAG laser (λ = 2.94 μm) was used to ablate the gallbladder epithelium of 24 prairie dogs; 20 sham-irradiated and 12 non-operated prairie dogs served as controls. Prairie dogs were sacrificed at time periods of 4 days, 2 weeks, and 8–12 weeks and evaluated for the presence of gallstones and cholesterol crystals. Laser-irradiated gallbladders demonstrated a lower rate of gallstone formation at 8–12 weeks than the sham-irradiated gallbladders (39% vs. 79%: P <.02). Crystal formation, however, was not different between laser-irradiated (88%) and sham-irradiated (100%) animals. The laser-irradiated group had less epithelium than the non-operated group at all time periods (P ≤.002) and compared to the sham-irradiated group at 4 days and 8–12 weeks (P ≤.001). These data suggest that laser ablation of gallbladder epithelium can reduce the rate of gallstone formation although this effect may be temporary. © 1994 Wiley-Liss, Inc.     

Gallstone formation in dogs after selective occlusion of the portal vein branches

The effects of selective portal blood interruption on gallstone formation were investigated experimentally in dogs. The gallstone incidence in group I (left portal vein occlusion, N=10) was 60 per cent at 1 month after the ligation, 64 per cent at 2 months (N=9) and 88 per cent at 3 months (N=8), whereas the incidence in group II (right portal vein occlusion, N=5) was 0 per cent at 1 and 2 months (N=5) after the ligation and 20 per cent at 3 months (N=5). All canine gallstones, which were similar to human black stones on morphological and infrared spectroscopic examination, formed only in the gallbladders of both groups. Bile analysis showed that cholesterol, phospholipids and total bile acid concentrations in the gallbladder bile were significantly decreased in group I after the ligation. Microscopy of the gallbladders in group I showed prominent PAS-positive material in the gallbladders. Gallstone formation after portal vein occlusion is thought to depend on the extent of the area of portal blood interruption.     

Predictors of gallstone formation after bariatric surgery: a multivariate analysis of risk factors comparing gastric bypass, gastric banding, and sleeve gastrectomy

Background  Risk factors for gallstone formation in the general population have been well studied while those after weight reduction surgery are unknown. The aim of this study was to identify the risk factors for the development of symptomatic gallstones after bariatric surgery. Method  Retrospective review was performed for patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGBP), adjustable gastric banding (LAGB) or sleeve gastrectomy (LSG) between 2004 and 2006. Statistical evaluation was performed using a univariate and multivariate analysis. Risk factors, including age, gender, preoperative body mass index (BMI), BMI > 45 kg/m², diabetes mellitus, hyperlipidemia, types of operation, and weight loss >25% of original weight, were analyzed for their association with postoperative symptomatic gallstones formation. Results  670 laparoscopic RYGBP, 47 LAGB, and 79 LSG were performed in our institute. Preoperative gallbladder disease, as indicated by presence of gallstones or sludge on preoperative transabdominal ultrasound, or previous cholecystectomy, were found in 25.3, 14.9, and 30.4% of patients who subsequently had RYGBP, LAGB, and LSG, respectively. A total of 586 patients were included for analysis. Mean follow-up was 25.9 (range 12–42) months. Overall rate of symptomatic gallstone formation was 7.8% and mean time for its development was 10.2 (range 2–37) months. Incidence of symptomatic gallstones with complications as initial presentation was found in 1.9% of the patients. Logistic regression analysis showed that only postoperative weight loss of more than 25% of original weight was associated with symptomatic gallstones formation [B = 1.482, SE = 0.533, odds ratio 4.44, 95% confidence interval (CI) 1.549–12.498, p = 0.005]. Conclusions  Traditional risk factors for gallstone formation in the general population are not predictive of symptomatic gallstone formation after bariatric surgery. Weight loss of more than 25% of original weight was the only postoperative factor that can help selecting patients for postoperative ultrasound surveillance and subsequent cholecystectomy once gallstones were identified. Accepted as poster, SAGES 2008 and presented April, 10–12th. An erratum to this article can be found at     

The effects of prosthetic gallstones on gallbladder function and bile composition

Diminished gallbladder emptying has been implicated in the pathogenesis of gallstone formation. This study assessed the effect of the physical presence of inert, prosthetic gallstones on gallbladder contractility, histopathology, and bile composition. Three glass beads, each 3 mm in diameter, were implanted in the guinea pig gallbladder. Six weeks later the in vitro contractility was assessed in response to cholecystokinin. Sham-operated animals underwent cholecystotomy without bead implantation. The gross and microscopic appearance of gallbladders from sham-operated and implanted animals was the same. The presence of stones moderately inhibited gallbladder contraction reaching 20.5% (P less than 0.05) at the maximally effective dose of cholecystokinin compared to sham-operated animals. Sham-operated and control (unoperated) animals had similar gallbladder contractility. Thus surgery itself did not alter gallbladder motility. The presence of stones had no effect on biliary lipid composition. It thus appears that gallstones, in the unobstructed gallbladder, cause only a moderate inhibition of gallbladder contractility and have little effect on biliary physiology.     

Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog

Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltose-dextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 +/- 1.25 versus 3.84 +/- 0.56; p less than 0.05) and the total calcium (3.37 +/- 0.24 versus 2.43 +/- 0.29; p less than 0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids.     

The effects of ethinylestradiol, a glucose diet and streptozotocin induced diabetes mellitus on gallstone formation and biliary lipid composition in the hamster

Possible risk factors for gallstone formation were examined and the concentrations of biliary lipids and each bile acid in the hepatic and gallbladder bile of hamsters were quantified. Forty female golden Syrian hamsters were divided into 4 groups according to diet; Group I, given control chow, Group II, given an ethinylestradiol and cholesterol supplemented diet, Group III, given a glucose rich diet without induced diabetes mellitus, and Group IV, given a glucose rich diet with diabetes mellitus induced by streptozotocin injection. The formation of cholesterol crystals but not gallstones was induced in Group II associated with a significantly decreased total bile acid concentration in the gallbladder bile but not in the hepatic bile. The formation of cholesterol gallstones and crystals with significantly higher concentrations of cholesterol and phospholipid was observed in Group III, while neither the formation of gallstones nor lithogenicity was enhanced by diabetes mellitus. However, a quite different lithogenicity was evident between the hepatic and gallbladder bile of the Group IV animals. These results suggest that neither the consumption of oral contraceptives nor diabetes mellitus induces gallstone formation, but that these factors can be responsible for dysfunction of the gallbladder.     

胆囊胆固醇结石与胆固醇息肉的关系研究

目的:探讨胆囊胆固醇结石与胆固醇息肉的关系.方法:抽样调查172例因胆囊结石和胆囊息肉行内镜保胆手术的患者(术后3年以上),其中胆囊结石119例,胆囊息肉39例,胆囊结石合并胆囊息肉14例,观察患者术后结石与息肉的复发情况.结果:119例胆囊结石患者中,术后结石复发22例,无新发息肉;39例胆囊息肉患者中,术后息肉复发3例,新发结石1例;14例胆囊结石合并胆囊息肉患者中,术后息肉复发2例,其中1例并结石复发;胆囊结石与胆囊息肉的复发率差异有统计学意义(P＜0.05).结论:胆囊胆固醇结石与胆固醇息肉可能是发病机制各异的相互独立的疾病,但胆囊息肉可能通过影响胆囊内胆汁流体的状态而影响胆囊胆固醇结石的形成,导致较高的术后复发率,故对合并胆囊息肉的胆囊结石患者不推荐保胆手术.     

Altered biliary prostaglandins and cholesterol gallstones: an in vivo study

Recent investigations suggest that biliary prostaglandin metabolism is altered during cholesterol gallstone formation. Most of the available data, however, has been obtained from in vitro studies. The purpose of the present study was to define the effects of cholesterol gallstone formation on in vivo biliary prostaglandin metabolism. Male prairie dogs were fed either a control chow for 21 days or a 1.2% cholesterol-enriched chow for 14-21 days. Cholecystectomy was performed and gallbladder tissue and bile were collected for analysis of prostaglandin concentrations using radioimmunoassay techniques. Gallbladder bile was examined for the presence of crystals and stones. No control animals but all cholesterol-fed animals developed either cholesterol crystals or gallstones (P less than 0.001). Concentrations of prostaglandin E2, prostaglandin F2 (PGF2 alpha), and the stable metabolic products of prostacyclin and thromboxane A2, 6-keto-PGF1 alpha and thromboxane B2 (TXB2), respectively, were decreased 60-85% in the gallbladder tissue of animals with crystals and gallstones compared to controls. Additionally, gallstone containing animals and those with crystals demonstrated a significant increase in the gallbladder bile concentrations of PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. These findings lend support to previously reported in vitro studies suggesting that prostaglandin synthesis increases at an early stage of experimentally induced cholesterol gallstone formation.     

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??Study on the relationship between gallbladder cholesterol polyps and the pathogenesis of gallstones JIAO Da-hai*, HAN Tian-quan, JIANG Zhao-yan, et al. *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Minimally Invasive Surgery Center, Shanghai 200025, China Corresponding author: WANG Ming-liang, Email: mingliangwang@hotmail.com Abstract Objective To study on the relationship between gallbladder cholesterol polyps and the pathogenesis of gallstone. Methods gallbladder stone, bile and part of gallbladder full-thickness tissue were collected from 62 patients who underwent laparoscopic cholecystectomy from April 2008 to september 2008 in our center, including 31 patients with gallbladder cholesterol polyps, 18 patients with cholesterol gallstones and 13 patients in control??6 patients with gallbladder adenoma and 7 patients with non-cholesterol gallstone ). sonography was applied to measure the gallbladder three diameter before and 1 hour after breakfast to evaluate the contracted function of gallbladder. The contents of cholesterol in gallstone and cholesterol, bile acid and phospholipid in bile were measured, and the full-thickness tissue of the gallbladder wall was done the pathological examination. Results Emptying Rate of Gallbladder in the patients with cholesterol polyps was(47.3±18.6) %, it was significantly decreased comparing with those that in the healthy people(71.7±8.1)%, P??0.01, but there ware no differences between the patients in group of cholesterol polyps and in group of gallstones??47.6±23.7??%. Cholesterol saturation index was higher in the patients with cholesterol polyps comparing with those that in control group(1.0±0.2 vs 0.6±0.3, P??0.01), but there ware no differences between the patients in group of cholesterol polyps and in group of gallstones (1.0±0.2 vs1.0±0.2, P??0.05). Gallstones and cholesterol polyps coexistence in 13 patients among 31 patients who with the gallbladder cholesterol polyps, and the incidence of gallstone is 41.9%. Conclusion the existence of gallbladder cholesterol polyps may lead to the formation of gallbladder stone.     

Pathogenesis of pigment gallstones in western societies: The central role of bacteria

Bacteria are traditionally accorded a greater role in pigment gallstone formation in Eastern populations. Stone color is thought to predict the presence of bacteria; that is, black stones (Western predominant) are supposedly sterile and brown stones (Eastern predominant) contain bacteria. We previously reported that, regardless of appearance, most pigment gallstones contain bacteria. This study examined, in a large Western population (370 patients), the incidence, appearance, and chemical composition of pigment stones, and the characteristics of gallstone bacteria. One hundred eighty-six pigment stones were obtained aseptically. Bacteria were detected by means of scanning electron microscopy and gallstone culture. Chemical composition was determined by infrared spectroscopy. Bacteria were tested for slime and β-glucuronidase production. Seventy-three percent of pigment stones contained bacteria. Choledocholithiasis was associated with gallstone bacteria. Ca-bilirubinate was present in all pigment stones. Capalmitate was characteristic of infected stones, and more than 75% Ca-carbonate was characteristic of sterile stones. Neither chemical composition nor stone appearance predicted the presence of bacteria. Ninety-five percent and 67% of infected pigment stones contained bacteria that produced slime and β-glucuronidase, respectively. Most pigment stones contained bacteria that produced β-glucuronidase, slime, and phospholipase, factors that facilitate stone formation. Thus bacteria have a major role in Western pigment gallstone formation. Furthermore, gallstone color did not predict composition or bacterial presence. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (oral presentation). Supported by a VA Merit Review Grant     

Interaction of chenodeoxycholic acid and dietary cholesterol in the treatment of cholesterol gallstones

Standard doses of chenodeoxycholic acid (15 mg/kg/day) fail to dissolve gallstones in 30 to 50 percent of patients with radiolucent gallstones in a functioning gallbladder. In humans, increasing dietary cholesterol produces increased biliary secretion of cholesterol. Restriction of dietary cholesterol reduces the minimum effective dose of chenodeoxycholic acid and speeds gallstone dissolution. In this study we investigated the interaction of dietary cholesterol and chenodeoxycholic acid in the prevention of gallstones in the prairie dog gallstone model. In animals fed a moderately lithogenic diet, standard doses of chenodeoxycholic acid failed to prevent gallstones. Reduction of the cholesterol stimulus or doubling the dose of chenodeoxycholic acid prevented the formation of gallstones. These findings support the hypothesis that the formation and dissolution of cholesterol gallstones are an expression of the relative strengths of saturating and desaturating stimuli. Therefore, rational therapy for cholesterol gallstone dissolution and prevention requires both reduction of lithogenic stimuli and optimal titration of chenodeoxycholic acid.     

CD68在胆囊壁中的表达及意义

目的观察CD68在胆囊壁中的表达和分布,探讨其与胆囊壁的脂质转运、胆固醇结石发病之间的关系。方法PV-9000免疫组化方法检测CD68在34例胆固醇结石病人、19例非胆囊结石病人及15例对照组胆囊壁标本中的表达。结果CD68表达主要分布在胆囊粘膜上皮细胞顶侧,胆固醇结石病人、非胆囊结石病人胆囊壁CD68的表达显著高于对照组,其差异有统计学意义（P〈0．05）。结论胆囊壁中CD68在胆囊胆固醇结石病人和非胆囊结石病人的表达上调,反映了胆囊壁对脂质的吸收和转运功能,与胆固醇结石的形成密切相关。     

Ezetimibe ameliorates cholecystosteatosis

BACKGROUND: Cholecystosteatosis is the accumulation of gallbladder wall fats leading to decreased gallbladder emptying. Ezetimibe inhibits intestinal fat absorption and prevents murine gallstone formation. However, the influence of ezetimibe on gallbladder emptying and cholecystosteatosis has not been studied. Therefore, we tested the hypothesis that ezetimibe would improve gallbladder motility by preventing the buildup of fats in the gallbladder wall. METHODS: Forty lean female mice were fed either a control diet or a lithogenic diet for 6 weeks. Half of the mice on each diet received ezetimibe. At 11 weeks of age, all mice were fasted overnight and underwent gallbladder ultrasonography to determine ejection fraction. One week later, the mice were fasted and underwent cholecystectomy. Bile was examined for cholesterol crystals. The gallbladders were snap-frozen for lipid analysis. RESULTS: The lithogenic diet significantly (P < 0.05) increased serum cholesterol, biliary crystals, gallbladder wall cholesterol and cholesterol/phospholipid ratio, and decreased gallbladder ejection fraction. All of these abnormalities were reversed (P < 0.05) by the addition of ezetimibe to the diet. CONCLUSIONS: These data suggest that ezetimibe lowers serum cholesterol, prevents biliary crystals, and normalizes gallbladder wall fat and function. We conclude that ezetimibe ameliorates cholecystosteatosis and may be an effective agent for gallstone prevention.     

瘦素对血脂及胆汁成分的调节在胆囊胆固醇结石形成中的作用

目的:分析胆囊胆固醇结石患者瘦素与血脂及胆囊内胆汁成分的关系,探讨瘦素在胆囊胆固醇结石形成中的作用。方法:选择胆囊胆固醇结石接受腹腔镜胆囊切除术的患者30例(结石组)与同期因胆囊息肉行腹腔镜胆囊切除术的患者22例(息肉组),检测患者血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、瘦素、胆囊胆汁中的TC与总胆汁酸(TBA)水平,以及胆囊壁组织瘦素受体mRNA水平。结果:与息肉组比较,结石组血清TC、TG、LDL、瘦素水平以及胆囊内胆汁TC/TBA含量比率与胆囊组织瘦素受体mRNA水平均明显升高,而血清HDL明显降低(均P0.05)。结石组的血清瘦素水平与血清TG、TC及胆汁TC均呈正相关(r=0.633,P=0.002;r=0.224,P=0.025;r=0.384,P=0.000),与HDL和TBA呈负相关(r=-0.205,P=0.014;r=-0.548,P=0.024)呈负相关,而息肉组血清瘦素与以上指标间均无关(均P0.05)。结论:瘦素参与了胆囊胆固醇结石的形成,瘦素及其受体水平的升高可能与胆囊胆固醇结石患者胆固醇代谢异常、胆囊胆汁成分失调密切相关。