针刺足三里对FD胃排空及血清Motilin和Ghrelin的影响

目的:观察针刺穴位足三里对功能性消化不良(Functional Dyspepsia,FD)促进胃排空的治疗作用及对照研究血清Motilin和Ghrelin的变化。方法:采用适度夹尾刺激法复制FD大鼠模型,分别予电针刺激足三里穴位及对照性西药治疗,测定各组大鼠摄食量、体重、胃残留率、碳末推进率及血清Motilin和Ghrelin浓度。结果:模型组、西药组和针刺组摄食量与空白组比较均显著下降;西药组与针刺组胃残留率减少;西药组和针刺组相应的碳末推进率较空白组显著升高;模型组大鼠血清Motilin浓度显著下降;模型组大鼠血清Ghrelin相对升高,但无统计学意义。结论:中医手法针刺足三里对胃肠动力有促进作用,可能与恢复功能性消化不良大鼠的Moti-lin、Ghrelin水平有相关性。

餐后不适综合征患者血浆Motilin与Ghrelin水平的测定

目的探讨血浆中Motilin与Ghrelin含量的变化与餐后不适综合征(Postprandial Distress Syndrome,PDS)型功能性消化不良的关系。方法将32例餐后不适综合征患者进行临床症状积分评价,分为轻、中、重三组。采用ELISA法测定32例餐后不适综合征患者血浆中Motilin与Ghrelin的含量,判断血浆中Motilin和Ghrelin的含量与餐后不适综合征发病及疾病严重程度的关系。结果餐后不适综合征患者血浆中Motilin与Ghrelin水平显著低于正常对照组(P<0.01),且临床症状积分高者明显低于临床症状积分低者(P<0.05)。结论餐后不适综合征患者血浆Motilin与Ghrelin水平降低,并与临床症状的严重程度密切负相关。

Simotang enhances gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice

AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.

Differences and significance of motilin,vasoactive intestinal peptide and gastrin in blood and gallbladder tissues of patients with gallstones

BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01). CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.

Effects of erythromycin on pressure in pyloric antrum and plasma motilin and somatostatin content in dogs

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猪Motilin和Ghrelin基因克隆及其真核载体的构建与体外表达

目的:克隆Motilin和ghrelin基因,构建表达Motilin的pDsRed-Express-motilin载体和表达ghrelin的pEGFP-ghrelin载体,并检测它们能否在真核细胞中表达及表达量的变化。方法:用RT-PCR方法分别从猪小肠和胃的cDNA上扩Motilin和ghrelin基因片段,并分别克隆到pDsRed-Express-N1载体和pEGFP-N1载体上,用脂质体法转染RIBS2细胞系(来自于肾),并用半定量RT-PCR和荧光成像法检测目的基因的表达。结果:构建了表达Motilin的pDsRed-Express-motilin和表达ghrelin基因的pEGFP-ghrelin载体,并能在真核细胞中超表达目的基因,为进一步相关研究提供了实验基础。

Preclinical and clinical studies on motilin

In the paper,we review our preclinical and clinical studies on motilin (MTL) in recentyears.Our studies have demonstrated for the first time that MTL was widely distributed in hu-man body fluids,fetal cerebrospinal fluid and digestive tract and have revealed that both humanand rabbit Mo cells(MTL-secreting cells)did secret intracavitarily.The endogenous MTL hadan accelerating effect on small bowel transmit time.Wheaten food taking could inhibit the releaseof MTL into plasma,and acupuncturing in certain acupoints could promote its secretion.The ris-es of plasma MTL levels were found in patients with liver cirrhosis,pregnant hypertension syn-drome or in stress state.MTL levels in plasma and gastroduodenal juices of gastric cancer pa-tients were elevated significantly;MTL levels in plasma were decreased in patients with non-ul-cer dyspepsia,bile-regurgitational gastritis or leukemia.We also probed into the phys-iopathological significance of changes in MTL levels in other human body fluids.

Plasma motilin concentration in the second and third trimesters of pregnancy and postpartum

Plasma motilin concentrations were measured in 135 women during the second andthird trimesters of pregnancy and 3～5 d after delivery and the results were compared withthose of 20 healthy nonpregnant women.The mean plasma motilin concentration (323.96±125.10 ng/L) in women during the second trimester of pregnancy was lower than in healthynonpregnant women (366.12±96.23 ng/L) (P【0.05),but that was significantly higher thanin women during the third trimester of pregnancy (121.04±27.00 ng/L) (P【0.01);theplasma motilin concentration in women during 3～5d after delivery (443.05±140.79 ng/L)was significantly higher than that in pregnant women (P【0.01).The results showed thatpregnancy appears to have a profound inhibitory effect on plasma motilin,and this may partlybe responsible for the gastrointestinal hypomotility associated with pregnancy.

梅山猪Ghrelin和Motilin基因克隆、结构分析及组织表达谱

分析克隆梅山猪Ghrelin和M otilin基因全编码序列并分析其核苷酸和氨基酸序列,系统研究它们的组织表达分布;用RT-PCR方法克隆梅山猪M otilin和Ghrelin基因全编码序列,并利用生物信息学和分子生物学技术相结合的方法分析它们的核苷酸和氨基酸序列;采用半定量RT-PCR技术检测梅山猪不同组织M otilin和GhrelinmRNA的相对丰度;显示,梅山猪Ghrelin和M otilin基因具有编码区cDNA单核甘酸多肽性(cSNPs);Gh-relin和M otilin基因呈广泛分布,在所取组织中均有不同程度的Ghrelin和M otilinmRNA表达。

Sphincter of Oddi hypomotility and its relationship with duodenal-biliary reflux,plasma motilin and serum gastrin

AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by mea-suring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoas-say. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of con-tractions (SOF), duration of contractions (SOD), duo-denal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the controlgroup (t = 5.254, 3.438 and 3.527, P < 0.001). SOD of the reflux group was shorter than the control group (t = 2.049, P < 0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t = -2.230 and -2.235, P < 0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastroin-testinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary re-flux.

The distribution of motilin receptor in the amygdala of rats and its role in migrating myoelectric complex

Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.

Effect of motilin and erythromycin on intracellular Ca2+ mobilization in rat myenteric neurons in culture

Objective: To investigate the effects of motilin and erythromycin on intracellular Ca2+ mobi-lization in cultured myenteric neurons of rats. Methods: The cultured myenteric neurons were identified with immunofluorescence staining technique. Motilin-induced and erythromycin-induced intracellular Ca2+ mobilization was studied in primary cultures of myenteric neurons using the ratiometric Ca2+ indicator Furo3/AM, with a laser confocal microscope. Results: The effects of motilin and erythromycin on intracellular Ca2+ mobilization were as follows: (1)In Hank's solution, 10 -8, 10-7, 10-6 mol/L motilin could elevate intracellular Ca2+ concentration ([Ca2+]i)in a dose-dependent manner. (2) In Hank's solution, 10μg/ ml erythromycin also could induce the elevation of [Ca2+]i. (3) After pretreatment with antibody against the motilin receptor in Hank's solution, the Ca2+ response to erythromycin was almost restricted. Conclusion: It is suggested that motilin could increase [Ca2+]i in myenteric neurons in a dose-dependent manner, and erythromycin may also have this effectivenesss by binding to the motilin receptor.

Effects of motilin in the hippocampus on the interdigestive migrating motor complex in rats

Objective:To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex (MMC) in rats. Methods: Adult SD rats of either sex were used; 0.5 μl motilin (0.74 mmol/L) was injected into the guide cannula which was stereotaxically implanted into the hippocampus previously. Then the MMC was recorded by a RM6240B multilead physiological recording system. Results: (1)MMC characteristics of normal rats’ duodenum: the frequency of phase Ⅲ was (18.1±0.4) bursts/min; the amplitude of phase Ⅲ was (260.5±42.3)μV; the duration of phase Ⅲ was (354.1± 21.6) s; MMC cycle duration was (690.2±58.7)s. (2) After motilin was injected into the hippocampus, the duodenal MMC cycle duration was decreased significantly. However, the amplitude of phase Ⅲ and the frequency of phase Ⅲ were increased. But there were no effects on the duration of phase Ⅲ. Frequency of phase Ⅲ percentage change was much more than amplitude of phase Ⅲ percentage change (57.2±2.8 vs 39.3±5.2). (3) Effects of motilin in the hippocampus on MMC were completely abolished by subdiaphragmal vagotomy. (4) Effects of motilin in the hippocampus on MMC were unaffected by intravenously injected atropine, phentolamine or propranolol. (5) The anti-motilin serum partly abolished the effects of motilin in the hippocampus on MMC. Conclusion: Motilin in the hippocampus has effects on the duodenal MMC cycle duration, the amplitude of phase Ⅲ and the frequency of phase Ⅲ. Motilin in the hippocampus plays an important role in duodenal MMC.

Effect of motilin on the contractility of gastric smooth muscle via NO pathway in guinea pigs

This study investigates the gastroprokinetic effects of motilin and erythromycin A (EM-A) and its potential mechanism in guinea pigs Cavia porcellus in vitro. Guinea pig stomach strips were mounted under organ baths containing Krebs solution. Motilin,EM-A,Nω-Nitro-L-arginine (L-NNA),L-arginine (L-AA) were added to the bathing solution in a non-cumulative way. Then the effects of motilin and EM-A was studied during electrical field stimulation (EFS) in the absence and presence of L-NNA and L-AA in the gastric anturm and fundus of guinea pigs. In addition,we observed the co-expression of motilin receptors and neuronal nitric oxide synthase (nNOS) in the gastric myenteric plexus of guinea pigs by fluo-immunohistochemistry. The results showed that the circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions with the frequency of 1-16 Hz. The on-responses induced a relaxation,partially mediated by the release of nitric oxide (NO) because addition of L-NNA turned the relaxations into cholinergically mediated contractions. The off-contractions were also cholinergically mediated as they disappeared under non-adrenergic,non-cholinergic (NANC) conditions using atropine and guanethidine. In fundic strips,motilin and EM-A induced on-relaxation and off-contraction and both motilin (1 μmol/L) and EM-A (100 μmol/L) may significantly increased on-response and reduced off-response (P<0.05). And the effects of motilin on strip responses were significantly enhanced compared with EM-A. The on-responses could be reversed into a cholinergically mediated contraction by addition of NOS inhibitors L-NNA. In contrast,administration of substrate of NOS,L-AA,significantly increased on-relaxations and reduced cholinergic motor responses which were induced by motilin or EM-A. However D-arginine (D-AA) did not change the above response induced by motilin or EM-A. In the antral strips,motilin and EM-A only increased off-contractions. The response to motilin and EM-A in the presence of L-NNA did differ from that obtained with L-NNA alone. It showed that both motilin and EM-A could enhance off-contractions induced by L-NNA (P<0.05). Immunohistochemistry study showed that motilin receptor immunoreactive positive neurons were co-localized with nNOS positive neurons in the gastric myenteric plexus of the guinea pigs. These results suggested that motilin or EM-A modulates gastrointestinal motility which was mediated by activating gastric nervous and NO pathways in guinea pigs gastro-intestinal

气滞胃痛颗粒对伴幽门螺杆菌感染功能性消化不良患者幽门螺杆菌清除率、胃肠动力的影响

目的探究气滞胃痛颗粒对伴幽门螺杆菌(Hp)感染功能性消化不良(FD)患者Hp清除率、胃肠动力的影响,以指导临床治疗措施拟定,促使伴Hp感染FD患者临床获益。方法选取2023年1月至6月赣州市人民医院接收的100例伴Hp感染FD患者作为研究对象,按随机数字表法分为对照组和观察组,每组各50例。对照组行常规西医治疗,观察组在此基础上加用气滞胃痛颗粒。评估两组疗效,统计两组Hp清除率,比较两组治疗前后的胃肠动力指标,对两组治疗期间不良反应进行统计。结果观察组总有效率、Hp清除率高于对照组,差异有统计学意义(P<0.05)。治疗4周,观察组瘦素、胃动素以及血清胃泌素均高于对照组,促肾上腺皮质激素释放激素(CRH)低于对照组,差异有统计学意义(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论在常规西药治疗基础上使用气滞胃痛颗粒可提高伴Hp感染FD患者的Hp清除率,改善其胃肠动力,疗效显著,且不会增加不良反应。

振腹环揉推拿法对失眠患者血清胃泌素、胃动素含量影响的临床研究

目的 探讨振腹环揉推拿法对失眠患者血清胃泌素、胃动素含量的影响。方法 在尊重临床伦理的前提下,招募40名胃失和降型失眠患者和20名健康志愿者,将40名患者随机分为治疗组和对照组,20名健康志愿者纳入健康组并未接受任何治疗;治疗组采取振腹环揉法进行治疗,每次30 min,每日1次;对照组采用保和丸口服,每次9 g,每日2次,5 d为1个疗程,共进行4个疗程;治疗前后,对2组患者的匹茨堡睡眠质量指数量表(PSQI)及阿森斯失眠量表(ASI)评分、胃泌素及胃动素检测结果进行统计学分析,并将胃泌素及胃动素检测结果与健康组进行对比。结果 2组治疗后与治疗前比较,各项数据均有明显改善,且治疗组较对照组改善明显,更接近健康组(P<0.05),差异具有统计学意义。结论 腹部推拿可显著地改善失眠患者的睡眠状态并提高睡眠质量,一定程度地提升了失眠患者的血清胃泌素及胃动素含量,进一步印证了“胃不和则卧不安”的经典理论的临床实用性。

子午流注法温灸联合穴位贴敷治疗功能性便秘的疗效观察

目的观察子午流注穴位温灸联合自拟软坚散神阙穴贴敷治疗功能性便秘的临床疗效及对患者血清胃动素(motilin,MTL)和5-羟色胺4受体(5-hydroxytryptamine serotonin receptor 4,5-HT4R)水平的影响。方法选取80例功能性便秘患者,用随机数字表法等分为对照组和研究组,每组40例。对照组用子午流注穴位温灸进行治疗,研究组用子午流注穴位温灸包联合自拟软坚散神阙穴贴敷治疗。比较两组临床疗效,观察两组治疗前后症状评分、直肠压力以及血清MTL、5-HT4R、神经型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)、一氧化氮(nitric oxide,NO)、血管活性肠多肽(vasoactive intestinal polypeptide,VIP)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷胱甘肽(glutathione r-glutamyl cysteingl glycine,GSH)水平的变化。结果研究组总有效率明显高于对照组(P<0.05)。治疗后,两组血清MTL和5-HT4R水平均高于治疗前(P<0.05),且研究组均高于对照组(P<0.05)。治疗后,两组临床症状评分以及血清nNOS、NO和VIP水平均低于治疗前,且研究组均低于对照组(P<0.05)。治疗后,两组直肠肛门抑制反射阈值和首次排便感觉阈值均低于治疗前(P<0.05),最大缩榨压和直肠静息压均高于治疗前(P<0.05);且研究组上述指标均优于对照组(P<0.05)。治疗后,两组血清MDA水平均低于治疗前(P<0.05),血清SOD和GSH水平均高于治疗前(P<0.05);且研究组上述指标均优于对照组(P<0.05)。结论在常规治疗基础上,子午流注穴位温灸联合自拟软坚散神阙穴贴敷治疗功能性便秘的临床疗效优于单一温灸包治疗,可提高血清MTL和5-HT4R水平,缓解临床症状和直肠压力,改善血清肠神经递质、SOD、MDA和GSH水平。

基因重复在基因选配(gene co-option)过程中的重要作用:对motilin/ghrelin荷尔蒙基因家族及其受体基因家族的进化研究

原先存在的基因经过一些改良可能获得新的属性从而承担新的功能.在分子遗传的层次,这个过程通常伴随基因重复以及基因重复后旁系同源基因的功能分化.本研究探索了基因重复后荷尔蒙、受体间特异性相互作用的演化形成.尽管对这个问题已有相关研究报道,但针对更多个案的研究能帮助我们更好地理解此前已经提出的进化模型的普遍性,可能还有助于发现新的进化模式.基于生物信息学的手段,结合比较基因组学、系统发育学的方法,本研究揭示,ghrelin前体基因和motilin前体基因是由一个祖先基因重复而来,基因重复发生在羊膜动物与两栖动物刚刚分歧之后.与此形成鲜明对照,它们各自的特异性受体却呈现了很不一样的进化历史.GPR39最先分化出来,而后一个祖先基因经连续的基因重复分化为鱼类特异的进化支A,GHSR和MLNR,基因重复发生在射线鳍鱼(ray-finned fish)与四足动物分化之前.ghrelin/GHSR信号系统的功能从鱼类到哺乳动物的进化过程中始终保守.motilin-MLNR之间的特异性相互作用是荷尔蒙基因重复后,MLN与GHRL基因分化之后,在羊膜动物世系中配体与受体协同进化而形成的.该结果提示,在分子水平上,基于保守的分子元件,新的神经内分泌响应模式能够通过基因重复后的基因选配过程形成.基因重复既节俭又极具创造力,为生物多样性的演化提供了物质基础.

大黄芒硝外敷联合温针灸对腹腔镜阑尾切除术后康复的影响

目的探讨大黄芒硝外敷联合温针灸对腹腔镜阑尾切除术后患者胃肠功能恢复、腹胀程度、胃动素(MTL)、胃泌素(GAS)的影响。方法回顾性分析宜春浙赣友好医院2021年12月至2023年1月腹腔镜阑尾切除术患者100例临床资料,术后给予常规治疗50例作为对照组;在对照组基础上给予大黄芒硝外敷联合温针灸治疗的50例作为观察组。比较两组胃肠功能恢复指标、腹胀程度、MTL、GAS及并发症发生率。结果治疗后,观察组肠鸣音恢复时间、首次排气时间、首次排便时间均短于对照组;观察组腹胀程度轻于对照组;观察组血清MTL、GAS水平均高于对照组,差异均有统计学意义(P<0.05)。观察组并发症总发生率(6.00%)低于对照组(20.00%),差异有统计学意义(P<0.05)。结论大黄芒硝外敷联合温针灸可有效地改善腹腔镜阑尾切除术后胃肠蠕动功能,促进胃肠功能恢复,减轻腹胀程度,降低并发症发生率。