胆囊在胆固醇结石形成中的作用研究进展(文献综述)

胆囊是胆固醇结石形成的场所。胆固醇结石形成并不完全依赖于胆汁的物理化学成分改变 ,胆囊功能改变在胆固醇结石形成中起重要的作用。本文从胆囊粘膜功能异常、胆囊收缩功能异常、胆囊结石与肠道功能改变几个方面作一综述。     

胆囊在胆固醇结石形成中的作用研究进展（文献综述）

胆囊是胆固醇结石形成的场所,胆固醇结石形成并不完全依赖于胆汗的物理化学成分改变,胆囊功能改变在胆固醇结石形成中起重要的作用,本文从胆囊粘膜功能异常,胆囊收缩功能异常,胆囊结石与肠道功能改变几个方面作一综述。     

胆囊胆固醇结石形成与载脂蛋白E基因多态性的关系

载脂蛋白Ｅ(ＡｐｏＥ)由 3个等位基因 (ε2 、ε3、ε4)分别编码 3种异构体(ＡｐｏＥ2 、Ｅ3、Ｅ4) ,组成 6种表型 (Ｅ2 /2、Ｅ2 /3、Ｅ2 /4、Ｅ3/3、Ｅ3/4、Ｅ4/4)。本研究旨在探讨胆固醇结石形成与ＡｐｏＥ基因多态性的关系 ,现报道如下。一、材料与方法1 .标本来源 :本院胆囊胆固醇结石患者 40例 ,其中男 1 1例 ,女 2 9例 ,平均年龄 ( 52± 4)岁。正常对照组为门诊体检者 ,共 60例 ,其中男 1 6例 ,女44例 ,平均年龄 ( 50± 4)岁。2 .方法 :( 1 )ＡｐｏＥ基因多态性检测 :基因组ＤＮＡ提出 :取外周静脉血5ｍｌ,乙二胺四乙酸 (ＥＤＴＡ)抗…     

载脂蛋白E与胆囊胆固醇结石关系的研究

目的 探讨载脂蛋白Ｅ（ａｐｏｌｉｐｏｐｒｏｔｅｉｎ Ｅ）基因多态性与胆囊胆固醇结石形成的关系。方法 应用聚合酶链反应（ＰＣＲ）技术检测６０例健康人和４０例胆囊胆固醇结石患者的Ａｐｏ Ｅ基因多态性及等位基因频率。结果 胆囊胆固醇结石患者Ａｐｏ Ｅ基因型Ｅ３／４的频率２３％（９／４０）明显高于健康对照组７％（４／６０）（Ｐ〈０．０５）,胆囊胆固醇结石患者组ε４等位基因频率为１５％（１２／８０）,明显高     

前列腺素E2防止废用性骨质疏松症

大鼠右后肢经弹力绷带固定于腹部后,分别给于不同时期、不同剂量的前列腺素E_2(PGE_2)治疗。与年龄对照组及固定不治疗组相比,PGE_2虽然引起松质骨的侵蚀以及皮质骨的稀疏,但却能刺激编织骨及板层骨形成及骨外膜、骨内膜新骨形成。因之,PGE_2可以防止废用性骨丢失。     

α-亚麻酸对草酸钙结石鼠前列腺素E2的影响

目的：探讨前列腺素E2在尿结石形成中的作用以及α-亚麻酸对前列腺素E2的抑制作用。方法：将60只雄性Wistar成年大鼠随机分成空白对照组、成石组、苏子油组、葵花籽油组。所有大鼠适应性喂养1周后，空白对照组随后7周均饮用自来水。成石组前4周饮用自来水，后3周饮用诱石剂水，每日自来水2g／只灌胃1次。苏子油组7周内每日以苏子油2g／只灌胃1次，饮水同成石组。葵花油组7周内每日以葵花油2g／只灌胃1次，饮水同B组。8周后检测大鼠24h尿总钙、尿总镁、尿草酸、肌酐和各组大鼠尿前列腺素E2水平。结果：空白对照组和苏子油组尿总钙明显低于成石组。尿总镁、尿草酸对照组明显低于成石组，苏子油组、葵花籽油组、成石组之间则差异无显著性意义。尿肌酐对照组、苏子油组、葵花油组显著低于成石组。24h尿前腺素E2水平苏子油组、对照组显著低于成石组。葵花籽油组与成石组比较差异无显著性意义。成石组、苏子油组、葵花籽油组前列腺素E2水平与尿总钙含量成正相关性。结论：前列腺素E2可能参与并促进了尿结石的形成，α-亚麻酸可能通过抑制肾前列腺素E2的产生而抑制尿结石形成。     

前列腺素E1防治大鼠急性坏死性胰腺炎的作用及机理

目的：研究前列腺素Ｅ１防治大鼠急性坏死性胰腺炎的作用及其机理。方法：向大鼠胰管内注射５％的牛磺胆酸钠溶液制成急性坏死性胰腺炎（ＡＮＰ）模型。结果：ＡＮＰ时，且腺毛细血管通透性（ＰＣＰ）明显增高，胰腺组织中性粒细胞过氧化酶（ＭＰＯ）活性及脂质过氧化物（ＬＰＯ）水平明显增高。病理示组织内大量ＰＭＮ浸润、片状出血、坏死。ＰＧＥ１使ＰＣＰ明显下降，ＭＰＯ、ＬＰＯ显著降低，动物存活明显改善结论：ＰＧＥ１通过     

前列腺素E2（PGE2）在椎间盘突出物中的含量

腰椎间盘突出常合并有炎症。作为一种生物化学性或免疫性的刺激物。突出的间盘组织可引起临床症状。硬膜外间隙注入髓核匀装组的大所产生的全身及局部炎症改变较注入等渗盐水对照组的光更为显著。生物化学、免疫学及介质因素所涉及的发病机制至今尚未明了。且相应地在矫形外科文献中亦较少受到关注。令人不解的就是为什么有些椎间盘突出有疼痛,而另一些部无疼痛。Saal曾显承在四间盘突出物的酸性提取物中有异常高水平的活性磷酯酶A2。此酶是炎症区域细胞表面前列腺素和白三烯产生的限速酶。E族前列腺素与炎症具有最强的相关关系。作者本研…     

前列腺素E2转导力学信号对骨形成的影响

骨细胞对流体剪切力、压力、磁场力、重力等作出重要生物信号反应之一是释放大量激素,其中前列腺素E2的影响作用十分显著。成骨细胞在受到力学刺激后膜表面的蛋白多糖迅速接收信号、微管剪切应力增大及细胞产生变形,使得成骨细胞释放一氧化氮和前列腺素E2增加。前列腺素E2通过对破骨细胞前体细胞表达的核因子-κB受体活化因子配体进行调控,刺激破骨细胞分化,抑制其凋亡,还可与细胞中其他细胞因子相互调节来维持成骨细胞与破骨细胞的平衡,最终实现其对骨形成的作用。     

外源性前列腺素E2对兔跟腱胶原含量的影响

目的肌腱损伤后周围前列腺素E2(prostaglandin E2,PGE2)及体外牵伸载荷条件下肌腱细胞产生的PGE2均升高,通过观察外源性PGE2对兔跟腱胶原含量的影响,探讨其与肌腱病发生的关系。方法取健康3～4月龄日本短耳兔24只,体重2.0～2.5 kg,雌雄不限;根据PGE2注射剂量不同随机分为两组(n=12):低剂量组(50 ng)和高剂量组(500 ng)。随机选择一侧后肢跟腱中部经皮注射0.2 mL对应剂量PGE2,对侧对应部位注射0.2 mL生理盐水作为对照,每周注射1次至处死。注射4、8周后两组各处死6只实验动物,大体观察跟腱情况后,取双侧跟腱HE染色观察细胞结构、基质形态,苦味酸-天狼星红染色偏振光显微镜下观察肌腱组织的胶原变化并定量分析Ⅰ、Ⅲ型胶原含量,透射电镜观测胶原纤维密度及直径。结果 HE染色示两组实验侧均出现胶原纤维结构破坏。苦味酸-天狼星红染色示4、8周时两组实验侧Ⅲ型胶原纤维均较对照侧增加,Ⅰ型胶原减少(P<0.05);与低剂量组比较,高剂量组实验侧Ⅲ型胶原纤维增加,Ⅰ型胶原减少,Ⅲ/Ⅰ型胶原比值增高(P<0.05)。透射电镜示两组4、8周时实验侧单位面积内总胶原纤维横截面积所占百分比均较对照侧降低,直径>100 nm的纤维比例均较对照侧降低,直径<100 nm的纤维比例均增加(P<0.05);与低剂量组比较,高剂量组实验侧单位面积内总胶原纤维横截面积所占百分比更低,直径>100 nm的纤维比例均明显降低,直径<100 nm的比例明显增加(P<0.05)。结论重复注射PGE2能导致兔跟腱Ⅰ型胶原减少,Ⅲ型胶原增多,Ⅰ/Ⅲ型胶原比例倒置,单位面积总胶原纤维密度降低,直径变细,可能与肌腱病发生相关。     

Research progress on the immune microenvironment of the gallbladder in patients with cholesterol gallstones

Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades. However, the mechanism of cholesterol gallstone formation is not fully understood, so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones. The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors, among which genetic susceptibility, intestinal microflora disorders, impaired gallbladder motility, and immune disorders are important in the pathogenesis of cholesterol gallstones. This review focuses on recent advances in these mechanisms. We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones, which may be hot areas in the future.     

丁酸与胆固醇型胆结石形成的关系

胆结石是临床上最常见并且多发的消化系统疾病之一,是一种受遗传、环境、饮食等多因素影响的胆道系统疾病。其发病因素多样且临床症状不一,主要以右上腹疼痛为主要特征。随着社会的进步以及人们生活水平的提高,其发病率呈逐渐上升趋势。目前关于通过药物和手术治疗胆结石的研究越来越多,但仍存在复发率高、并发症多等弊端。近来有研究表明,肠道菌群代谢产物短链脂肪酸对胆固醇型胆结石的形成有一定的影响。笔者就其中一种短链脂肪酸—丁酸与胆固醇型胆结石形成关系的研究现状做一综述。     

豚鼠胆囊胆固醇结石形成过程中胆囊Cajal样间质细胞及动力的变化

目的 观察豚鼠胆囊胆固醇结石形成过程中胆囊组织Cajal样间质细胞(ICLCs)及胆囊动力的变化.方法 将100只豚鼠随机分为实验组与对照组,每组50只,实验组给予致石饲料(胆固醇含量2％),对照组给予正常颗粒饲料,8周造模结束后,利用胆囊全层铺片免疫荧光化学染色及激光共聚焦显微镜观察各组ICLCs数量的变化,利用透射电镜观察各组胆囊组织中ICLCs的超微结构特征,利用在体胆囊收缩素(CCK-8)激发实验评价胆囊动力的变化.结果 对照组豚鼠胆囊ICLCs平均阳性面积为(18.37±0.64)％,实验组为(2.47±0.28)％,较对照组明显降低(t=21.122,P＜0.01);对照组豚鼠胆囊胆汁时间-流量曲线下面积为(31.58 ±2.26)μl,实验组为(15.02±1.98)μl,较对照组明显降低(t=8.586,P＜0.01).结论 饮食诱导的豚鼠胆囊胆固醇结石形成过程中,胆囊ICLCs明显减少,同时胆囊动力受损,对外源性CCK反应下降.胆囊动力受损可能与ICLCs减少有关.     

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.     

Prostaglandin E2 enhances alveolar bone formation in the rat mandible

Prostaglandin E₂ (PGE₂) induces bone formation in stress-bearing bones. The mandible, a stress-bearing bone, is loaded daily during mastication. The aim of this study was to determine if PGE₂ delivered locally to the mandible over 20 days enhances alveolar bone deposition. In 18 Lewis rats, controlled-release pellets containing PGE₂ were implanted on the buccal aspect on the left-hand side of the mandible, mesial to the root of the first molar. Controlled-release pellets locally delivered 0.1, 0.05, or 0.025 mg/day of PGE₂. The right side of the mandible was used as a matched control for each animal. Six sham-treated animals were implanted with a placebo pellet. On days 7 and 19, animals were injected with the bone markers tetracycline and calcein, respectively. On day 21, animals were sacrificed and undecalcified tissues obtained for morphometrical analysis. Morphometrical measurements were analyzed by paired t test to determine differences between the matched samples and one-way ANOVA to compare the different treatment groups. A significant increase in alveolar bone area was observed in mandibles treated with 0.1 and 0.05 mg/day when compared with matched controls and the placebo group. This was accompanied by a significant increase in alveolar bone height and width. The proportions of double-labeled surface (dLS), the mineral apposition rate (MAR), and bone formation rate (BFR) were significantly increased in mandibles treated with the two higher doses of PGE₂. The proportion of resorptive surface (RS) was significantly reduced in these two groups. It is concluded that PGE₂ induces alveolar bone formation in the mandible when locally delivered at a dose of 0.1 or 0.05 mg/day for 20 days.     

The possible role of prostaglandin E2 in urinary stone formation

To investigate the role of prostaglandin E2 in urinary stone formation, urinary prostaglandin E2 was measured by radioimmunoassay in 28 men with recurrent idiopathic urolithiasis (14 normocalciuric and 14 hypercalciuric patients) and 6 healthy male volunteers. Urinary prostaglandin E2 levels were significantly higher (p less than 0.01) in the hypercalciuric group than in the normocalciuric and healthy control groups, and they showed a positive correlation with urinary calcium excretion. Urinary prostaglandin E2 and calcium excretions in the hypercalciuric and normocalciuric groups were suppressed significantly by indomethacin. Creatinine clearance was not reduced by indomethacin. The results suggest that renal prostaglandin E2 may participate in calcium stone formation by regulating the renal tubular handling of calcium.     

前列腺素E_1阴茎海绵体内注射治疗功能性早泄初步报告

４０例功能性早泄病人，年龄２８～４０岁。病史半年，分成Ａ、Ｂ两组，每组２０例。Ａ组采用１０～２０μｇ前列腺素Ｅ１（ＰＧＥ１）阴茎海绵体注射；Ｂ组应用３％的丁卡因软膏阴茎头局部涂抹，每周治疗２次，疗程４周，停止治疗后１个月随访，结果显示：Ａ组治愈１３例（６５％），有效５例（２５％），疗效优于Ｂ组，无严重副作用，说明采用ＰＧＥ１阴茎海绵体注射是治疗功能性早泄的一种安全、有效的方法。     

前列腺素E2在突出腰椎间盘中的表达及其与坐骨神经痛的关系

目的探讨前列腺素(PG)E2在突出腰椎间盘组织中的表达及其在坐骨神经痛发病机制中的作用。方法 42个突出椎间盘标本取自42例腰椎间盘突出并有坐骨神经放射性疼痛症状的手术治疗患者,其中膨隆型12例,破裂型15例,游离型15例,取材部位为紧贴神经根突入椎管的椎间盘组织(A部位)和椎间隙内残存的椎间盘组织(B部位)。术前采用视觉模拟评分(VAS)对所有患者坐骨神经痛严重程度进行评分。应用酶联免疫吸附试验(ELISA)检测PGE2含量。结果 A部位PGE2含量自膨隆型、破裂型至游离型逐渐升高,差异有显著性(P<0.01);A部位PGE2含量高于B部位(P<0.01);PGE2含量与患者坐骨神经痛VAS评分存在明显相关性(r=0.848,P<0.01)。结论 PGE2参与了腰椎间盘退变、突出的发病机制,PGE2含量与坐骨神经痛程度呈正相关性。