类胰升血糖素肽—1在大鼠和胎儿胰腺中分布的研究

为了研究类胰升血糖素肽－１在大鼠和胎儿胰腺中的分布情况，应用免疫组织化学ＡＢＣ法，对大鼠和胎儿胰腺中ＧＬＰ－１进行研究。结果表明，ＧＬＰ－１免疫反应物存在大于大鼠和胎儿胰岛的周边部。     

GLP—1—IR细胞在大鼠和成人肠道的分布

目的：研究比较GLP－1－IR细胞（L细胞）在大鼠和成人肠道的分布情况;方法：应用免疫组织化学SP法,评估细胞在Wistar大鼠和成人肠道中的分布。结果：肠道各段都可见L细胞,大鼠肠道中L细胞密度最大是回肠,成人肠道中密度最大是直肠,结论：不同种属间GLP－1－IR细胞密度不同,分布规律相同,即从小肠和大肠的近端向远端细胞密度逐渐增大。     

白芍总甙对大鼠腹腔巨噬细胞产生肿瘤坏死因子的影响

采用Ｌ９２９细胞株细胞毒检测法，观察了白芍总甙（ＴＧＰ）对ＬＰＳ诱导大鼠腹腔巨噬细胞（ＭΦ）产主肿瘤坏死因子（ＴＮＦ）的影响。结果表明、亚适量ＬＰＳ（５ｍｇ·Ｌ－１）诱导大鼠腹腔ＭΦ培养上清在６ｈ对Ｌ９２９细胞杀伤百分率最大．ＴＧＰ（２．５ｍｇ·Ｌ－１）能促进ＬＰＳ诱导大鼠腹腔ＭＯ产生ＴＮＦ，但不改变其动力学过程。ＴＧＰ（０．５～２５０ｍｇ·Ｌ－１）对ＬＰＳ诱导ＭΦ产生ＴＮＦ量效曲线呈钟罩形．提示ＴＧＰ对ＭΦ产主ＴＮＦ具有浓度依赖性双向调节作用。不同浓度ＴＧＰ对Ｌ９２９细胞无直接杀伤作用，亦无ｒｈＴＮＦ－α拮抗作用。     

灵芝菌丝体多糖通过增强小鼠巨噬细胞功能诱导HL-60细胞凋亡

目的探讨灵芝菌丝体粗总多糖（ＭＧＬＰ１）、总多糖（ＭＧＬＰ２）作用的小鼠腹腔巨噬细胞培养上清对ＨＬ－６０细胞凋亡的影响。方法ＭＧＬＰ１、ＭＧＬＰ２作用于小鼠腹腔巨噬细胞,生物法检测培养上清中ＴＮＦ－α的活性;再将共培养上清（ＭＧＬＰ１－ΜΦ－ＣＭ、ＭＧＬＰ２－ΜΦ－ＣＭ）作用于ＨＬ－６０细胞,ＭＴＴ法检测ＭＧＬＰ１－ΜΦ－ＣＭ、ＭＧＬＰ２－ΜΦ－ＣＭ对ＨＬ－６０细胞增殖的抑制作用;琼脂糖凝胶电泳法和流式细胞检测法定性定量检测它们对ＨＬ－６０细胞凋亡的诱导作用。结果ＭＧＬＰ１、ＭＧＬＰ２作用于腹腔巨噬细胞后,可以明显增强培养上清中ＴＮＦ－α的活性;其共培养上清可以明显地抑制ＨＬ－６０细胞的增殖并诱导该细胞凋亡（Ｐ＜０．０１）。结论ＭＧＬＰ１、ＭＧＬＰ２可以通过小鼠腹腔巨噬细胞,促进ＴＮＦ－α分泌,诱导ＨＬ－６０细胞凋亡。     

GLP—1—IR细胞在人类胎儿和成人胃肠道的分布

目的：对国人胎儿和成人类胰升血糖素－1免疫反应细胞（GLP－1－DR细胞）在胃肠道中的分布作详细的研究。方法：应用高特异性单克隆抗GLP－1－IR（7－36）酰胺抗体,采用免疫组化技术。结果：发现在胎儿和成人的肠管中均可见到GLP－1－IR细胞（L细胞）的存在,但在生长发育的不同时期肠道L细胞的密度不同,各段肠管的密度也不同,但不同时期的L细胞的分布规律相同,均自小肠和大肠的近段向远端逐渐增大,密度最大为直肠。结论：人类肠道中的GLP－1－IR细胞分布规律不变,密度增大。     

白芍总甙对大鼠腹腔巨噬细胞产生肿瘤坏死因子的调节机制

目的：研究不同浓度白芍总甙（ＴＧＰ）调节大鼠腹腔巨噬细胞（ＭΦ）产生肿瘤坏死因子（ＴＮＦ）作用。方法：在ＭΦ培养系统中有或无环氧酶抑制剂和钙调蛋白抑制剂等工具药，测定４５Ｃａ内流、ＰＧＥ２和ＴＮＦ含量。结果：ＴＧＰ（０．５～１０ｍｇ·Ｌ－１）明显促进ＬＰＳ诱导ＭΦ的４５Ｃａ内流和ＴＮＦ产生。线性回归分析表明，４５Ｃａ内流和ＴＮＦ产生呈明显正相关。三氟拉嗪（４０μｍｏｌ·Ｌ－１）可阻断ＴＧＰ促进ＬＰＳ诱导ＭΦ产生ＴＮＦ。ＴＧＰ－ＬＰＳ的ＴＮＦ释放曲线呈钟罩形，而ＴＧＰ－ＬＰＳ的ＰＧＥ２产生曲线呈浓度依赖性升高。当ＴＧＰ在低浓度（０．５～１２．５ｍｇ·Ｌ－１）时，ＴＮＦ与ＰＧＥ２产生明显正相关，而高浓度（１２．５～２５０ｍｇ·Ｌ－１）两者呈明显负相关。吲哚美辛（１０μｍｏｌ·Ｌ－１）可使ＴＮＦ量效曲线下降支消失，而Ｎω亚硝基－Ｌ－精氨酸（１５μｍｏｌ·Ｌ－１）对此无明显影响。结论：低浓度ＴＧＰ对ＴＮＦ产生上调作用可能与促进４５Ｃａ内流，提高钙调蛋白活性从而促进ＰＧＥ２分泌等有关，而高浓度下调作用是可能与ＭΦ自身产生大量ＰＧＥ２介导有关。     

白芍总甙对B淋巴细胞增殖和白介素1生成的调节作用

白芍总甙（ＴＧＰ）对脂多糖（ＬＰＳ）诱导的小鼠脾淋巴细胞增殖反应的量效曲线呈钟形，用贴壁法除去脾细胞中巨噬细胞（ＭΦ）或加入１０μｍｏｌ·Ｌ１吲哚美辛（Ｉｎｄ）可使ＴＧＰ量效曲线的下降支消失，再加５％同系小鼠腹腔ＭΦ中或前列腺素Ｅ２（ＰＧＥ２）０．０２２０μｍｏｌ·Ｌ１可使量效曲线下降支再现．同步检测ＴＧＰ对ＬＰＳ诱导大鼠腹腔ＭΦ产生ＰＧＥ２与白介素１（ＩＬ１）．结果表明，ＴＧＰ０．５－３ｌ２．５μｇ·ｍＬ１对ＬＰＳ诱导的ＩＬ－１产生曲线呈钟形．而ＴＧＰＬＰＳ的ＰＧＥ２产生曲线呈浓度依赖性地增高；在１２．５－３１２．５μｇ·ｍＬＴＧＰ范围内，１０μｍｏｌ·Ｌ１Ｉｎｄ可使高浓度ＴＣＰＬＰＳ的ＩＬ－１释放曲线明显抬高。提示ＴＧＰ对ＬＰＳ诱导的Ｂ细胞增殖反应和ＩＬ－１诱生的负调节作用都与其促进ＭΦ释放ＰＧＥ２有关．     

松果体对正常及佐剂性关节炎大鼠免疫细胞的影响

采用松果体切除（ＰＸ）及腹腔注射外源性褪黑素（ＭＴ）的方法，观察松果体对正常及佐剂性关节炎（ＡＡ）大鼠免疫细胞的影响。结果发现，ＰＸ后，ＣｏｎＡ及ＬＰＳ诱导的淋巴细胞增殖反应在正常及ＡＡ大鼠明显降低；正常大鼠ＬＰＳ诱导的腹腔巨噬细胞产生的白细胞介素Ｉ（ＩＬ－１）减少，而ＡＡ大鼠的ＩＬ－１明显增加。ＭＴ（１０μｇ·ｋｇ－１）作用则与此相反，并能使ＰＸ引起的免疫指标的改变恢复正常。上述结果表明；松果体对免细胞的功能有调节作用。     

吸烟对慢性阻塞性肺疾病脂质过氧化系统及α1—抗胰蛋白酶的影响

吸烟对慢性阻塞性肺疾病（ＣＯＰＤ）患者体内自由基水平和α１－抗胰蛋白酶的影响。采用硫代巴比妥法、放射免疫法和酶标法对３５例吸烟和２５例非吸烟ＣＯＰＤ患者血清脂质过氧化物（ＬＰＯ）、超氧化物歧化酶ＳＯＤ）、α１－ＡＴ和α１－酸性糖蛋白（α１－ＡＧ）进行测定。结果显示：吸烟ＣＯＰＤ组血中ＬＰＯ、α１－ＡＧ明显高于非吸烟组，ＳＯＤ、α１０－ＡＴ明显低于非吸烟组；吸烟组ＬＰＯ和α１－ＡＴ呈负相关，ＳＯＤ和     

癌胚抗原检测对肺癌诊断的临床应用

癌胚抗原(CEA)是一非特异性广谱肿瘤标记,1965年由加拿大 Gold 与 Freedman 首先发现。最初从成人结肠腺癌和胎儿肠道组织中提取出的 CEA 被认为是结/直肠癌的特异性肿瘤标记,其后大量研究表明,CEA 不仅存在于结/直肠等消化道肿瘤组织与2～6个月龄的胎儿胃肠道组织中,     

Measurement of unscheduled DNA synthesis on alkylating carcinogens in rat intestinal mucosal cells from different sites

Unscheduled DNA synthesis (UDS) induced by in vitro exposure to five alkylating carcinogens was measured in the mucosal cells from three different sites of the rat intestine. The yield of UDS by N-methyl-N'-nitro-N-nitrosoguanidine or N-ethyl-N'-nitro-N-nitrosoguanidine or methylazoxymethanol acetate was higher in the cells of colon & rectum than in those of the jejunum or ileum. Conversely, UDS induction by N-methyl-N-nitrosourea or methyl-methanesulphonate was seen at a rather higher level in the cells from the small intestine compared with those from the colon & rectum.     

胰高血糖素样肽-1受体激动剂治疗2型糖尿病的研究进展

胰高血糖素样肽-1（GLP-1）为末端空肠、回肠及结肠中L细胞分泌的葡萄糖依赖性的内源性肠促胰岛素分泌激素,依其可与胰岛β细胞膜上受体特异性结合促进β细胞增殖、分化、抑制其凋亡,增加胰岛β细胞数量,改善胰岛β细胞功能的作用而被视为治疗2型糖尿病（T2DM）新靶点的又一突破性发现。本文就目前FDA批准上市的胰高血糖素样肽-1受体激动剂（GLP-1 RAs）有关受体分布特点、作用机制、临床疗效及不良反应作一综述。     

Distribution of glucuronidation capacity (1-naphthol and morphine) along the rat intestine

The distribution of glucuronidation capacity along the rat intestine was investigated using mucosal cells, isolated from the small intestine, the caecum, and the colon plus rectum. The glucuronidation capacity for 1-naphthol decreases from 787 +/- 75 (duodenum) to 128 +/- 13 (colon plus rectum) pmoles/min X mg cell protein. The ratio between 1-naphthol and morphine glucuronidation was constant throughout the intestine (7.15 +/- 0.37). The distribution of maximal activity of UDP-glucuronosyltransferase in intestinal cell homogenates follows the same pattern. The maximal activity of UDPglucose dehydrogenase in homogenates corresponds closely to the glucuronidation rate in mucosal cells. The activity of beta-glucuronidase in intestinal cell homogenates is constant along the duodenum and jejunum but increases throughout the terminal ileum, caecum, colon and rectum. Subcellular fractionation studies using marker enzymes indicate that UDPglucose dehydrogenase and beta-glucuronidase are cytosolic enzymes in intestinal mucosal cells. Although UDP-glucuronosyltransferase activity is found in both the mitochondrial and the microsomal fractions, no indications for a mitochondrial localization of this enzyme can be found. Activity in the mitochondrial fraction appears to be due to endoplasmic reticulum, associated with the mitochondrial fraction.     

The effects of excitatory amino acids on isolated gut segments of the rat.

Glutamate and aspartate are excitatory neurotransmitters in both central and peripheral nervous systems, acting on ionotropic and metabotropic receptors. In our study we have examined the effects of glutamate, aspartate, N-methyl-d-aspartate (NMDA), kainic acid and (+/-)-1-aminocyclopentane-cis-1,3-dicarboxylic acid (ACPD) on tone and spontaneous activity of isolated rat gastric fundus, jejunum, ileum, ascending colon and rectum. Both glutamate and aspartate produced concentration-dependent tonic contractions of rat fundus and rectum; the other gut segments used in the study were not responsive. While only NMDA and kainic acid produced concentration-dependent tonic contractions of isolated rat gastric fundus, all three type-selective agonists of glutamate receptors (NMDA, kainic acid and ACPD) produced tonic contractions of isolated rat rectum. The results of our study suggest that glutamate and aspartate in rat gastric fundus activate excitatory intrinsic neurons through only ionotropic receptors (NMDA and non-NMDA receptors), while the same action in rat rectum is mediated through both ionotropic and metabotropic receptors.     

The effects of nifedipine and verapamil on high K+ induced contractions of the rat intestinal tract in vivo

The effects of intravenous nifedipine and verapamil against the contraction produced by topical application of 54 mM K+ on the outer surface of rat duodenum, jejunum, ileum, caecum, colon and rectum have been investigated. Both drugs exhibited a descending gradient of relaxant activity with the exception of the rectum, verapamil being 1/3-1/4 as potent as nifedipine in all the test systems studied. Since these drugs at effective spasmolytic doses significantly affect heart rate and systemic blood pressure, their use as smooth muscle relaxants in intestinal disturbances would present several drawbacks.     

Comparative bioassay of prostaglandin E2 and its three pulmonary metabolites.

The relative potencies of prostaglandin E2 and its metabolites 15-keto PGE2, 13,14-dihydro-15-keto-PGE2 and 13,14,dihydro-PGE2 were investigated on isolated smooth muscle preparations. These were rat stomach strip, colon and uterus, chick rectum, guinea-pig ileum, trachea and pulmonary artery and rabbit aorta and pulmonary artery. 15-keto PGE2 was equiactive or 1-1.8 times more potent than prostaglandin E2 in relaxing guinea-pig trachea but otherwise the three metabolites were less active than prostaglandin E2 on all preparations.     

Glucagon like peptide-2 induces intestinal restitution through VEGF release from subepithelial myofibroblasts

Glucagon like peptide-2 (GLP-2) exerts intestinotrophic actions, but the underlying mechanisms are still a matter of debate. Recent studies demonstrated the expression of the GLP-2 receptor on fibroblasts located in the subepithelial tissue, where it might induce the release of growth factors such as keratinocyte growth factor (KGF) or vascular endothelial growth factor (VEGF). Therefore, in the present studies we sought to elucidate the downstream mechanisms involved in improved intestinal adaptation by GLP-2. Human colonic fibroblasts (CCD-18Co), human colonic cancer cells (Caco-2 cells) and rat ileum IEC-18 cells were used. GLP-2 receptor mRNA expression was determined using real time RT-PCR. Conditioned media from CCD-18Co cells were obtained following incubation with GLP-2 (50-250 nM) for 24 h. Cell viability was assessed by a 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT)-assay, and wound healing was determined with an established migration-assay. Transforming Growth Factor beta (TGF-beta), VEGF and KGF mRNA levels were determined by RT-PCR. Protein levels of VEGF and TGF-beta in CCD-18Co cells following GLP-2 stimulation were determined using ELISA. Neutralizing TGF-beta and VEGF-A antibodies were utilized to assess the role of TGF-beta and VEGF-A in the process of wound healing. GLP-2 receptor expression was detected in CCD-18Co cells. Conditioned media from CCD-18Co cells dose-dependently induced proliferation in Caco-2 cells, but not in IEC-18 cells. Conditioned media also enhanced cell migration in IEC-18 cells (P<0.01), while migration was even inhibited in Caco-2 cells (P<0.0012). GLP-2 significantly stimulated mRNA expression of VEGF and TGF-beta, but not of KGF in CCD-18Co. The migratory effects of GLP-2 were completely abolished in the presence of TGF-beta and VEGF-A antibodies. GLP-2 exerts differential effects on the epithelium of the small intestine and the colon. Thus, in small intestinal cells GLP-2 stimulates wound repair, whereas no such effects were observed in colonic cells. The mechanisms underlying GLP-2 induced intestinal wound repair seem to involve the secretion of VEGF and, subsequently, TGF-beta from subepithelial fibroblasts, whereas KGF appeared to be less important.     

A comparative study of functional 5-HT4 receptors in human colon, rat oesophagus and rat ileum.

1. The pharmacological properties of 5-hydroxytryptamine (5-HT), the 5-HT4 receptor agonists, DAU 6236 and SC 53116 and the 5-HT4 receptor antagonist, GR 1130808, were studied in the rat oesophagus, rat ileum and human colon. 2. 5-HT relaxed the longitudinal muscle of the rat oesophagus and rat ileum and the circular muscle of the human colon. Absolute values of relaxation were measured and showed the order of the maximum responses, rat oesophagus >> human colon > rat ileum with EC50 values of 189 +/- 15 nM, 157 +/- 4 nM, 306 +/- 72 nM, respectively. 5-HT also inhibited the spontaneous contractions of the human colon with an EC50 value of 119 +/- 1 nM. The effect of 5-HT on the human colon was not affected by methysergide (10 microM) or ondansetron (1 microM). 3. The use of the uptake and metabolism inhibitors, cocaine (30 microM) and pargyline (100 microM), did not increase the potency of 5-HT in the rat oesophagus or human colon. In the rat oesophagus, cocaine (30 microM) produced a reduction in carbachol-induced tone of 22.2 +/- 0.6% and reduced the 5-HT maximum effect by 52.0 +/- 0.4%. 4. The compounds, DAU 6236 and SC 53116, showed a different pattern of potencies and efficacies in the rat oesophagus, rat ileum and human colon compared to 5-HT. DAU 6236 relaxed the human colonic circular muscle with an EC50 value of 129 +/- 16 nM but its efficacy was less than that of 5-HT. DAU 6236 (1 microM) also antagonized the 5-HT-induced relaxation of the human colon with a dose-ratio of 9.9. In the rat oesophagus and rat ileum, DAU 6236 was inactive in the majority of tissues. In the minority of oesophagus tissues that did respond the EC50 value was 1.2 +/- 0.7 microM. DAU 6236 also antagonized the effect of 5-HT in the rat oesophagus in a non-surmountable fashion. SC 53116 relaxed the rat oesophagus with an EC50 value of 91 +/- 4 nM, with an efficacy less than that observed to 5-HT; however, at 200 nM it did not antagonize the 5-HT-induced relaxation of the rat oesophagus. SC 53116 showed no agonist activity in the rat ileum and human colon, but at 1 microM it did antagonize the effect of 5-HT in the human colon with a dose-ratio of 11.3 +/- 0.3.(ABSTRACT TRUNCATED AT 400 WORDS)