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.     

CCK-8通过豚鼠胆囊ICC样细胞上CCK-A受体引起胆囊收缩

目的研究胆囊ICC样细胞上CCK-A受体的表达及意义,以及CCK-8通过胆囊ICC样细胞上的CCK-A受体对胆囊平滑肌运动的调节作用。方法采用免疫荧光双标法,检测c-kit和CCK-A受体在胆囊组织切片及分离细胞培养片上的共同表达;肌条试验观察CCK-8通过ICC样细胞对胆囊肌条的收缩作用。结果胆囊组织切片免疫荧光双标显示,c-kit和CCK-A受体共同表达于胆囊肌层,胆囊分离细胞培养片显示ICC样细胞表面c-kit表达阳性,胞体和突触均明显着色,细胞呈多角形,部分细胞发出长突起,与相邻ICC样细胞连接成网络状,部分细胞突触末端形成细丝。胆囊ICC样细胞同时高度表达CCK-A受体。CCK 1×10-6～1×10-10mol/L可使胆囊平滑肌产生剂量依赖性收缩,而缺少ICC样细胞的胆囊平滑肌对CCK-8的反应降低。结论胆囊ICC样细胞高度表达CCK-A受体,CCK-8可能通过ICC样细胞上的CCK-A受体调节胆囊的运动。     

自拟疏肝利胆汤治疗胆囊结石36例

[目的]观察自拟疏肝利胆汤治疗胆囊结石的临床疗效.[方法]72例胆囊结石患者随机分为2组,各36例,对照组予熊去氧胆酸口服,治疗组予自拟疏肝利胆汤治疗,均治疗2个月.分别于治疗前、后B超检测观察胆囊结石胆囊排空率变化以及综合疗效的评价.[结果]治疗组痊愈20例、显效10例、好转3例、无效3例,对照组依次为5、6、3、22例,治疗组总有效率(91.67％)高于对照组(38.89％)(P＜0.01)；2组治疗后胆囊排空率均较治疗前好转,但治疗组疗效更为显著(P＜0.01)；治疗组结石排净率(61.11％)优于对照组(16.67％)(P＜0.01).[结论]自拟疏肝利胆汤可以明显改善胆囊的收缩功能和提高结石排净率,其作用略优于熊去氧胆酸,是治疗胆囊结石的有效方剂.     

胆囊结石患者胆囊壁CCK-AR mRNA表达及血浆CCK-8水平与胆囊排空功能的关系

目的探讨胆囊结石患者胆囊收缩素(CCK)-A受体(AR)mRNA表达及血浆CCK-8水平与胆囊排空功能的关系。方法60例胆囊结石患者(结石组)和30例无胆囊结石而行上腹部手术者(对照组),术前用B超测定胆囊排空功能,RT-PCR技术检测胆囊壁CCK-ARmRNA,放射免疫法检测血浆CCK-8。结果结石组CCK-ARmRNA为0.59±0.11,与对照组的0.91±0.06相比,P<0.01;结石组中,胆囊收缩减弱者的CCK-ARmRNA为0.52±0.06,与收缩正常者的0.70±0.07相比,P<0.01;结石组血浆CCK-8为(42.91±2.88)pmol/L,与对照组的(31.50±1.62)pmol/L相比,P<0.05;结石组术前血浆CCK-8为(42.91±2.88)pmol/L,与术后的(34.21±2.56)pmol/L相比,P<0.05。结论CCK-AR、CCK-8在胆囊运动调节中发挥重要作用。     

弥可保对糖尿病并发自主神经病变患者胆囊收缩功能的影响

将63例糖尿病并发自主神经病变患者随机分为两组,对照组采用常规治疗,治疗组在此基础上加用弥可保;治疗前后观察两组患者的胆囊体积和胆囊收缩率。结果显示,与对照组比较,治疗组胆囊体积明显缩小,胆囊收缩率明显升高(P均<0.05)。提示糖尿病并发自主神经病变可引起胆囊收缩功能障碍,弥可保能有效改善其胆囊收缩功能。     

胆胃舒冲剂对胆囊息肉摘除术后复发的影响

[目的]观察利胆健脾中药胆胃舒冲剂对保胆息肉摘除术后患者息肉复发的影响.[方法]将138例患者随机分成2组,对照组单纯采用保胆内镜息肉摘除术治疗,治疗组在内镜摘除术治疗基础上加服利胆健脾中药胆胃舒冲剂.1年后观察2组息肉复发情况、胆囊收缩功能及胆囊壁厚度.[结果]治疗组对胆囊壁厚度、胆囊收缩功能(相对收缩率)方面的影响优于对照组(P＜0.01)；治疗组未发现息肉复发,对照组复发1例.[结论]胆胃舒冲剂能增强胆囊收缩功能及使胆囊壁厚度变薄,能预防胆囊息肉的复发.     

胆囊收缩素受体及胆囊运动与胆囊结石形成相关性研究进展

胆囊结石是消化系统的常见病 ,国内外多年的研究已证实胆囊结石的形成与胆囊运动功能障碍有密切的关系。为了从分子水平更进一步地探讨胆囊结石的成因 ,近年来国内外学者开始了对胆囊收缩素受体的研究。通过一系列的研究发现 ,胆囊收缩素受体的变化影响胆囊的运动功能 ,从而导致胆囊结石的形成。     

防石胶囊预防胆囊结石复发的临床研究

[目的]观察中药防石胶囊预防微创保胆内镜取石术后患者胆囊结石复发的效果。[方法]将178例行微创保胆取石术后患者随机分成对照组及治疗组,每组89例,分别予不同治疗,2年后计算胆囊壁的厚度及胆囊收缩功能的变化。[结果]治疗组胆囊壁厚度显著低于对照组,收缩功能则高于对照组（P〈0.01）,对照组有3例结石复发。[结论]防石胶囊能减轻及消除胆囊壁的炎症,增强胆囊的收缩功能,有助于防止胆囊结石的复发。     

逍遥散加减联合电针治疗胆囊切除术后综合征的临床观察

[目的]观察逍遥散加减联合电针治疗胆囊切除术后综合征的临床疗效.[方法]将116例患者随机分为治疗组和对照组各58例.治疗组以逍遥散加减联合电针辨证治疗;对照组口服利胆消炎片治疗.2组疗程均为1个月,观察2组治疗前后临床疗效.[结果]治疗后2组腹疼、腹胀,恶心、腹泻等症状比较,治疗组临床总有效率为93.10％,对照组为41.38％,2组比较差异有统计学意义(P＜0.05).[结论]逍遥散加减联合电针治疗胆囊切除术后综合征具有较好的临床疗效.     

缬草提取物对胆囊结石治疗作用与肝、胆囊组织内TNF及IL—1水平的关系

目的：探索缬草提取物对胆囊结石的治疗作用与肝、肝囊组织内肿瘤坏死因子（TNF）及白细胞介素－1（IL－1）水平的关系。方法：大耳白种家兔，手术植入胆固醇结石。实验组喂缬草提取物，对照组灌喂等容、等渗蒸馏水溶液。8周后，手术取出胆囊结石称重，测量肝脏、胆囊组织中TNF、IL－1水平，胆囊壁做组织学。结果：实验组结石平均重量较对照组明显为轻（P＜0．01）；结石消失率达75％。实验组肝组织内TNF、IL－1水平与对照组比较无明显差异（P＞0．05）。胆囊组织内TNF、IL－1水平明显低于对照组（P＜0．01）。对照组的胆囊组织呈明显炎性改变，实验组的胆囊组织则基本正常。结论：缬草提取物对胆囊胆固醇结石有明显的治疗作用，其作用与囊组织内TNF及IL－1水平有关。     

Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors on gallbladder interstitial cells of Cajal

AIM： To identify the cholecystokinin （CCK）-A receptors （CCK-AR） on the guniea pig gallbladder interstitial cells of cajal （ICC） and to study CCK-8 induced gallbladder muscle strip contractions through the CCK-AR.
METHODS： The existence of CCK-AR was examined by immunohistofluorescence on sectioned tissue and cultured cells. In vitro contractile response of guinea pig gallbladder muscle strips and the strips with ICC removed were also studied with CCK-8 receptors added.
RESULTS： In tissue sections, intensely CCKAR- immunoreactive interstitial cells were found mainly in the muscular layers. In cultured cell sections, distinctive double staining of C-kit and CCK-AR ICCs were found. When we removed the ICC of the gallbladder, CCK-8 induced muscle strip contraction dose response curve significantly shifted to the right.
CONCLUSION： We proved that both the existence of CCK-AR on the guinea pig gallbladder ICC and CCK evoked contraction are mediated through direct action on CCK-AR on the gallbladder ICC.     

双气消滞散对G豚鼠致石后胆囊调宁蛋白的影响

[目的]探讨双气消滞散促进胆管动力的作用机制。[方法]将受试豚鼠随机分为4组,即正常组、模型组、双气消滞散(中药)组、熊去氧胆酸(西药)组。后3组采用高胆固醇致石食饵诱发法建立豚鼠胆结石动物模型,并使其发生继发性胆囊运动功能障碍,其中中药组、西药组分别给予相应药物进行实验性治疗,连续7周后,分别对引起实验性豚鼠胆囊运动功能障碍的胆囊组织调宁蛋白(Cap)表达进行观察。[结果]中药组能有效促进胆囊动力(与模型组比较P<0.01),并且其效果优于西药组(P<0.01)。模型组动物胆囊组织Cap表达水平较正常组显著升高(P<0.01),中药组和西药组胆囊组织Cap表达水平虽均高于正常组(分别P<0.01、<0.05),但与模型组比较,其水平均明显降低(均P<0.01),且中药、西药2组胆囊组织Cap表达水平比较差异无统计学意义(P>0.05)。[结论]双气消滞散能显著促进胆囊动力,其作用机制可能与下调胆囊平滑肌组织Cap水平,提高胆囊平滑肌收缩能力有关。     

Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer

Background and Aim:  Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A ( CCK-AR ) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK-AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK-AR Pst I polymorphism in gallstone disease with gallbladder cancer.
Method:  This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.
Results:  The frequency of the A1A1 genotype of CCK-AR was significantly higher in gallstone patients than healthy individuals ( P  = 0.008 odds ratio [OR] = 2.25, and 95% confidence interval [CI]:1.2–4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients ( P  = 0.041, OR = 0.49, and 95% CI: 0.3–0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed.
Conclusion:  The results suggest that the A1A1 genotype of CCK-AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer.     

开胃进食汤超微配方颗粒对脾虚大鼠胃肠平滑肌钙调蛋白mRNA表达的调节作用

[目的]研究开胃进食汤超微配方颗粒对脾虚大鼠胃肠平滑肌细胞钙调蛋白（CAM）mRNA表达的影响,探求其对大鼠胃肠动力调节作用的可能机制。[方法]采用利血平致脾虚模型,大鼠随机分为正常组、模型组、开胃进食汤超微配方颗粒（超微）组、传统汤剂（传统）组和健胃消食片对照（健胃）组,用逆转录一聚合酶链反应（RT-PCR）半定量分析,观察各组CaMmRNA表达情况。[结果]模型组大鼠胃窦平滑肌内CaMmRNA表达明显减少,空肠平滑肌内明显增强（P〈0．05）;健胃组、传统组和超微组胃窦平滑肌内CaMmRNA表达较模型组增强（P〈0．05）,传统组和超微组空肠平滑肌内CaMmRNA表达低于模型组（P〈0．05,〈0．01）。[结论]开胃进食汤超微配方颗粒能促进胃窦平滑肌收缩和空肠平滑肌舒张,可能与其能明显提高胃窦平滑肌组织内和降低空肠平滑肌组织内CaMmRNA水平表达有关。     

Estrogen receptor alpha-induced cholecystokinin type A receptor expression in the female mouse pituitary

Estrogen plays a critical role in inducing LH surge. In the pituitary, estrogen receptor alpha (ERalpha) mediates the action of estrogen, while the downstream pathway of ERalpha activation is yet to be elucidated. Here, we report the finding that cholecystokinin type A receptor (CCK-AR) is an ERalpha downstream gene in the mouse anterior pituitary. In the cycling mouse pituitary, the expression of CCK-AR mRNA is markedly higher in the afternoon of proestrus compared with metestrus. Both ovariectomy (OVX) and null mutation of the ERalpha gene completely abolish CCK-AR mRNA expression. Injection of 17beta-estradiol to OVX wild-type mice induces recovery of CCK-AR mRNA expression to levels observed at proestrus, but no such recovery is induced in OVX ERalpha knockout mice. The same pattern of estrogen dependency in inducing CCK-AR mRNA expression was seen in cultured primary anterior pituitary cells, indicating that estrogen directly acts on pituitary cells to induce CCK-AR expression. Immunohistological analysis revealed that more than 80% of gonadotrophs express CCK-AR in the afternoon of proestrus. To test whether CCK-AR mediated the sensitizing effect of estrogen in GnRH-induced LH secretion, primary pituitary cells were primed with estrogen followed by treatment with GnRH in the presence or absence of lorglumide, a CCK-AR antagonist. While both groups secreted LH upon GnRH treatment, lorglumide treatment significantly decreased LH secretion. Taken together, this study finds CCK-AR to be an ERalpha downstream gene in the pituitary and suggests that CCK-AR may play a role in the estrogen sensitization of the pituitary response to GnRH.     

PTEN和P16基因蛋白在胆囊癌组织中的表达

[目的]探讨PTEN和P16基因蛋白在胆囊癌组织中表达的意义。[方法]应用免疫组织化学技术检测58例胆囊腺癌、20例胆囊腺瘤和20例慢性胆囊炎组织中PTEN和P16基因蛋白表达。[结果]胆囊癌患者PTEN和P16表达阳性率分别为43．1％（25／58）和37．9％（22／58），其表达阳性率均明显低于胆囊腺瘤和慢性胆囊炎（P〈0.05）。PTEN和P16表达与胆囊癌的分化程度、浆膜浸润和转移相关（P〈O．05）。[结论]检测PTEN和P16基因蛋白表达可作为评估胆囊癌生物学行为和预后的参考指标。     

Differential roles for cholecystokinin a receptors in energy balance in rats and mice

Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes. The lack of CCK-AR in Otsuka Long-Evans Tokushima fatty (OLETF) rats results in hyperphagia and obesity. We have suggested that demonstrated increases in meal size and elevated levels of dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) gene expression may contribute to this phenotype. In contrast to OLETF rats, CCK-AR(-/-) mice have normal total daily food intake and do not develop obesity. To assess the basis underlying the different phenotypes in rats and mice lacking CCK-AR, we characterized meal patterns in CCK-AR(-/-) mice and determined whether CCK-AR(-/-) mice exhibited an alteration in DMH NPY gene expression. We demonstrate that although CCK-AR(-/-) mice show a similar dysregulation in meal size as OLETF rats, they do not have an elevation in DMH NPY mRNA expression levels. In fact, intact mice have no CCK-AR in the DMH. Furthermore, in intact rats, NPY and CCK-AR are colocalized in DMH neurons, and parenchymal injection of CCK into the DMH reduces food intake and down-regulates DMH NPY mRNA expression. These results suggest that although CCK-AR plays a role in the mediation of CCK actions in the control of meal size in both rats and mice, CCK-AR seems to contribute to modulating DMH NPY levels only in rats. The deficit in CCK's action in the control of DMH NPY gene expression may play a major role in the obese phenotype in OLETF rats.     

Lack of Cholecystokinin-A Receptor Enhanced Gallstone Formation: A Study in CCK-A Receptor Gene Knockout Mice

The etiology of gallstones is multifactorial, with interactions between genes and the environment. We generated cholecystokinin (CCK) -A receptor (R)-deficient (–/–) mice and found that CCK did not produce gallbladder contraction in CCK-AR(–/–) mice. The purpose of this study was to identify the role of CCK-AR on gallstone formation. Age-matched CCK-AR gene (+/+) and (–/–) progenies were used. Sludge and gallstone formation, as well as plasma cholesterol levels, were measured at 12 and 24 months of age. Sludge and gallstone formation were significantly higher in CCK-AR(–/–) mice than in CCK-AR(+/+) mice at 12 and 24 months of age, although these were not different between 12 and 24 months of age. The plasma cholesterol levels, daily food intake, and body weight were not significantly different between CCK-AR(+/+) and (–/–) mice. Sludge and gallstone formation were not observed at 6 months of age. In conclusion, deteriorated gallbladder contraction due to a lack of CCK-AR favored gallstone formation after the middle age of life.