当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床研究

目的探讨当归龙荟片联合普芦卡必利治疗慢性功能性便秘的临床疗效。方法选取2018年5月-2019年5月在北京市肛肠医院治疗的慢性功能性便秘患者122例,根据用药的差别分为对照组(61例)和治疗组(61例)。对照组口服琥珀酸普芦卡必利片,2mg/次,1次/d;治疗组在对照组基础上口服当归龙荟片,4片/次,2次/d。两组患者均经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、PAC-QOL积分、结肠传输试验积分、Bristol和SF-36评分,及血清5-羟色胺(5-HT)、血管活性肠肽(VIP)、P物质(SP)和一氧化氮(NO)水平。结果治疗后,对照组和治疗组临床有效率分别为80.33%和96.72%,两组比较差异具有统计学意义(P<0.05)。经治疗,两组症状积分均明显降低(P<0.05),且治疗组比对照组降低更明显(P<0.05)。经治疗,两组患者PAC-QOL积分和结肠传输试验积分明显降低(P<0.05),而Bristol和SF-36评分明显升高(P<0.05),且治疗组患者明显好于对照组(P<0.05)。经治疗,两组患者血清SP、5-HT水平均显著升高(P<0.05),而VIP和NO水平均明显降低(P<0.05),且治疗组患者SP、5-HT、VIP和NO水平明显优于对照组(P<0.05)。结论当归龙荟片联合普芦卡必利治疗慢性功能性便秘可有效改善患者临床症状,促进患者生活质量改善,具有一定的临床推广应用价值。     

VIP能神经、生长抑素、5－HT阳性细胞与淋巴组织在人肠的分布

应用免疫组织化学方法，观察人肠相关淋巴组织血管活性肠肽（ＶＩ－Ｐ），神经特异性烯醇化酶（ＮＳＥ）及Ｓ－１００蛋白神经元神经纤维支配以及合５－羟色胺（５－ＨＴ）阳性细胞、生长抑素（ＳＳ）内分泌细胞分布。结果显示肠道相关淋巴，在聚集淋巴组织周围有神经肽ＶＩＰ及ＮＳＥＳ－１００蛋白阳性神经元神经纤维分布并穿插于淋巴细胞之间，淋巴滤泡中心有Ｓ－１００蛋白阳性树突状细胞。ＳＳ、５－ＨＴ阳性细胞分布于回肠和结肠粘膜上皮及腺体，在聚集淋巴组织元上粘膜上皮及腺体内ＳＳ、含５－ＨＴ阳性细胞数减少，与周围粘膜阳性细胞数相比差异有显著性（Ｐ＜０．０１），结果提示肠道神经，内分泌和免疫系统之间有密切关系。     

调肝理脾方治疗腹泻型肠易激综合征及对患者血浆血管活性肠肽 神经肽水平的影响

目的:观察调肝理脾方治疗腹泻型肠易激综合征(D-IBS)患者的临床疗效及对患者血浆血管活性肠肽(VIP)、神经肽(NPY)水平影响。方法:92例患者随机分为两组(各46例),治疗组采用调肝理脾方治疗,对照组采用得舒特治疗,疗程结束后观察和评价患者疗效情况,及治疗前后血浆VIP、NPY水平变化,另选30例体检健康者作正常对照。结果:治疗组总有效率91.30%,疗效优于对照组(72.61%)(P<0.05),血浆VIP、NPY水平在治疗组治疗前后比较有显著性差异(P<0.05),在对照组治疗前后比较差异无统计学意义(P>0.05)。结论:调肝理脾方对D-IBS有较好的近期疗效,能调节血浆VIP、NPY分泌异常情况。     

Priapism induced by intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate

This is a case of priapism (21 h) following an intracavernosal injection of vasoactive intestinal polypeptide (VIP) 25 mcg with phentolamine mesylate (PM) 1 mg responding to venesection and intracavernosal injection of 1 mg metaraminol.     

Measurement of vasoactive intestinal peptide using a competitive fluorescent microsphere immunoassay or ELISA in human blood samples

The concentration of Vasoactive Intestinal Peptide (VIP) as measured by recycling immunoaffinity chromatography (RIC) has been reported to be elevated in the blood of patients with autism as compared with normal subjects. In this study, we have developed a “Competitive Fluorescent Microsphere Immunoassay” (cFMI) in which VIP competes with biotinylated VIP in binding to polyclonal antibodies on microspheres. The results were obtained using the Luminex¹⁰⁰ system. We measured VIP in serum, plasma, and material eluted from dried blood spots on filter paper with both the cFMI and an ELISA procedure. We found that a purification procedure was necessary for obtaining useful results from plasma and serum, however, a preincubation step was required with the blood eluates. This newly developed cFMI was more sensitive (2.5 vs. 20.0 pg/ml), and more reproducible than the ELISA. To get accurate measurements of VIP in eluted material high sensitivity is especially important. Thus, the cFMI using the Luminex system has definite advantages over a conventional ELISA including the possibility that samples can be assayed at higher dilutions. We have determined that the VIP concentrations of serum, plasma, and dried blood spot eluate specimens as measured with the cFMI assay system were similar to those measured with ELISA. Thus, the new cFMI using Luminex system may be useful for detection of VIP in human blood samples.     

Receptors for VIP and PACAP in guinea pig cerebral cortex

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in guinea pig cerebral cortex were characterized by (1) radioreceptor binding of ¹²⁵I-labeled VIP (human/rat/porcine), and (2) cyclic AMP (cAMP) formation. Saturation analysis of ¹²⁵I-VIP binding to membranes of guinea pig cerebral cortex resulted in a linear Scatchard plot, suggesting the presence of a single class of high-affinity receptor-binding sites, with a Kd of 0.63 nM and a Bmax of 77 fmol/mg protein. Various peptides from the PACAP/VIP/secretin family displaced the specific binding of ¹²⁵I-VIP to guinea pig cerebrum with the relative rank order of potency: chicken VIP (cVIP) ≥ PACP38 ∼ PACAP27 ∼ guinea pig VIP (gpVIP) ≥ mammalian (human/rat/porcine) VIP (mVIP) > peptide histidine-methionine (PHM) > peptide histidine-isoleucine (PHI) > secretin. Analysis of the competition curves revealed displacement of ¹²⁵I-VIP from high- and lower-affinity binding sites, with IC50 values in the picomolar and the nanomolar range, respectively. About 70% of the specific ¹²⁵I-VIP-binding sites in guinea pig cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, cVIP, gpVIP, mVIP, PHM, and PHI stimulated cAMP production in [³H]adenine-prelabeled slices of guinea pig cerebral cortex in a concentration-dependent manner. Of the tested peptides, the most effective were PACAP38 and PACAP27, which at a 1 μM concentration produced a 17- to 19-fold rise in cAMP synthesis, increasing the nucleotide production to approx 11% conversion above the control value. The three forms of VIP (cVIP, mVIP, and gpVIP) at the highest concentration used, i.e., 3 μM, produced net increases in cAMP production in the range of 8–9% conversion, whereas 5 μM PHM and PHI, by, respectively, 6.7% and 4.9% conversion. It is concluded that cerebral cortex of guinea pig contains VPAC- type receptors positively linked to cAMP formation. In addition, the observed stronger action of PACAP (both PACAP38 and PACAP27), when compared to any form of VIP, on cAMP production in this tissue, suggests its interaction with both PAC1 and VPAC receptors.     

Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors in chick cerebral cortex

In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 > VIP6-28 (mammalian) > PHI (porcine) > neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 > VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors.     

Antagonism of VIP-stimulated cyclic AMP formation in chick brain

Of eight peptides tested (0.01-5 microM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 microM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1 microM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 microM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 microM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 microM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPACtype receptor-selective blocking activity.     

Two types of VIP neuronal components in rat suprachiasmatic nucleus

Vasoactive intestinal peptide (VIP) neurons constitute a large group in the suprachiasmatic nucleus (SCN) and it is thought that they are involved in the generation and entrainment of circadian rhythm. We have characterized these VIP-expressing neurons in rat SCN by their ability to induce the mammalian Period1 (Per1) gene in response to light exposure, innervation of retinal afferents, day-night variations in VIP mRNA, and coexpression of gastrin releasing peptide (GRP). VIP neurons in the ventrolateral SCN (SCNVL) were subdivided into two groups, light-evoked Per1-inducible main SCNVL (SCNVLmain) and non-Per1-inducible medially located SCNVL (SCNVLmed). Retinal innervation was abundant in the SCNVLmain but nearly absent in the SCNVLmed. Day-night variation in VIP mRNA expression level was observed in the SCNVLmain but not in the SCNVLmed. GRP mRNA was seen in rarely SCNVLmed but abundant in SCNVLmain, where some neurons coexpressed VIP mRNA. These findings indicate that VIP neurons in the SCN can be divided into two topographically and functionally distinct groups.