对牛胰多肽抑制胰酶分泌作用的离体研究

为探讨胰多肽抑制胰酶分泌的机制,我们利用大鼠离体胰腺泡制备观察了牛胰多肽(BPP)在细胞受体水平对氨甲酰胆碱等促分泌物作用的影响。实验结果显示,BPP 对氨甲酰胆碱诱导的胰腺泡淀粉酶分泌具有抑制作用,并存在剂量反应关系。BPP0.1μmol/L 和0.2μmol/L,可分别使氨甲酰胆碱诱导淀粉酶分泌的效价降低3倍和10倍;BPP 还可抑制氨甲酰胆碱刺激胰腺泡释放~(45)Ca。以上结果提示,BPP 对胰腺泡的胆碱能 M 受体具有拮抗作用。此外,BPP 对促胰液素及其同类激动剂和氨甲酰胆碱协同作用诱导的胰腺泡淀粉酶分泌具有抑制作用,提示胰多肽在整体对促胰液素诱导的胰酶分泌的抑制,可能是通过拮抗胰腺泡细胞上的 M 受体而抑制了促胰液素和胆碱能刺激协同作用引起的胰酶分泌。     

牛胰多肽对大鼠胰外分泌的抑制作用

在大鼠观察了牛胰多肽(BPP)对由蛋白胨和雨蛙素引起的大鼠胰外分泌的影响。向十二指肠灌入25%蛋白胨后90min 时,对照组的蛋白排出量约为其基础值的10倍,而1、3、5及10ug/kg BPP 剂量组的蛋白排出量分別为对照组的47%、33%、29%及29%。在灌注剂量为3μg/kg 雨蛙素后60min 时,对照组的蛋白排出量约为其基础值的14倍,但3、5及10μg/kgBPP 剂量组的蛋白排出量分別为对照组的74%、68%及55%。各组胰淀粉酶浓度的变化和其蛋白排出量变化相平行。胰液量的增加不受 BPP 影响。结果提示,BPP 能抑制胰酶的大量分泌,并有剂量依从关系,但不抑制胰液量。     

磷脂酶A与急性胰腺炎

一、胰腺炎与磷脂酶A 的关系磷脂酶A(phospholipase A,PA)广泛存在于人、鼠、荷兰鼠、牛、马、猪、羊、蛇及蜂等动物体内。在人体,它以不活化的酶前身形式主要分布于胰腺,随胰液分泌入十二指肠。近年来,PA 日益引起人们的关注,其一部分原因是与胰腺炎研究的进展分不开的。早在1868年,德国医生Klebs 认为胰蛋白酶能引起胰腺感染。1874年,Zenker 将胰腺感染称为急性胰腺炎,并报道胰腺炎可引起患者猝死,死因与胰腺出血有关。1875年,     

胰多肽对急性胰腺炎大鼠的细胞保护作用

用5%牛磺胆酸钠-胰蛋白酶溶液直接注入大鼠胰导管,制备成急性出血坏死性胰腺炎模型。由腹腔于制备前预防性地和制备后治疗性地结合注射剂量为3μg/kg 的牛胰多肽,能使病鼠的死亡率由对照的100%降到33%,已死鼠平均存活时间由对照的13±3小时延长到20±2小时,血清淀粉酶浓度升高的峰值降为对照的35%,胰腺组织学切片呈轻度急性胰腺炎或向慢性胰腺炎转化。单纯在制备前预防性地注射牛胰多肽或仅在制备后作治疗性注射,也有同样作用,但效果较差。这项结果提示,胰多肽对急性出血坏死性胰腺炎具有预防和治疗两方面的功效,即对胰腺有细胞保护作用。抑制胰酶的分泌和释放可能是它的作用机制之一。     

胰腺外分泌细胞的适应性细胞保护作用

用5％牛磺胆酸钠-胰蛋白酶溶液作为强刺激物直接注入大鼠胰导管系统,制成急性出血坏死性胰腺炎模型。若于48h前向胰导管内预先给予0.1％、0.2％或0.4％的低浓度牛磺胆酸钠-胰蛋白酶溶液作为弱刺激物,能使随后给予的强刺激物所致的损伤大大减轻,使病鼠死亡率由对照组的100％分别降低到27％、17％和17％;血清淀粉酶浓度升高的幅度由对照组的4680U/100ml血清降低到1990、2180和2710U/100ml血清。胰腺组织学切片检查可见,病变由急性出血坏死性胰腺炎转变为轻度急性胰腺炎或向慢性胰腺炎转化。这项结果提示:预先给予弱刺激可使胰腺外分泌细胞对随后给予的强刺激产生适应性细胞保护作用,其机制尚待探索。     

不同转移表型肺腺癌细胞PI-PLC的比较研究

实验证明钙、磷脂酰乙醇胺(PE)、磷脂酸(PA)及脱氧胆酸钠(DOC)对两种不同转移表型癌细胞磷脂酰肌醇特异的磷脂酶C(PI-PLC)的活性影响有明显差异。高转移性人肺腺癌细胞亚系(Anip_(973))比低或无转移性人肺腺癌细胞系(AGZY_(83-a))腹水型癌细胞PI-PLC活性高2.25—7.1倍。Anip_(1211)细胞培养液PI-PLC活性也大于AGZY_(83-a)。说明不同表型肺腺癌细胞具有不同性质的PI-PLC,且活性变化与转移表型密切相关。     

清胰汤对大鼠急性坏死性胰腺炎IL-6,IL-10 及肠道通透性影响

目的:探讨清胰汤改善大鼠急性坏死性胰腺炎(acute necrotizing pancreatitis)ANP炎症反应及肠道通透性功能的治疗效果及机制。方法:将72只雄性SD大鼠随机分为3组,其中2组大鼠采用从胰腺被膜下多点缓慢均匀注入3.8%牛黄胆酸钠(0.5ml/100g)建立大鼠急性坏死性胰腺炎模型,再分为急性坏死性胰腺炎常规治疗组(A组)、清胰汤干预治疗组(B组),其他24只大鼠为假手术组(S组),每组再随机分为24h、48h、72h组。各组于12h后给于肠内营养,B组肠内营养后给于2次清胰汤2.5ml/100g,A组、S组给于同等剂量生理盐水。各组于建模后24h、48h、72h处死,腹腔动脉取血检测血清淀粉酶浓度、IL-6、IL-10、D-乳酸水平。结果:48h时点B组IL-10水平较A组高(P<0.05);72时点B组血清淀粉酶水平较A组低(P<0.01),IL-6水平较A组低(P<0.01),IL-10水平较A组高(P<0.01),D-乳酸水平较A组低(P<0.01)。结论:清胰汤可以上调IL-10改善大鼠急性胰腺炎炎症反应从而降低肠道通透性。     

异搏定对小鼠肝癌腹水瘤细胞系PI-PLC活性的影响

本文采用615近交系小鼠肝癌腹水瘤H_(ca)-F_(25)/CL-A_2细胞,测定钙拮抗剂异搏定作用前后磷脂酰肌醇特异的磷脂酶C(PI-PLC)活性的变化,并与同样处理的瘤株内钙恒稳的有关指标相比较。结果表明经异搏定处理后的A_2细胞PI-PLC活性显著降低,并与钙恒稳的指标基本呈现相应的平行变化趋势。提示PI-PLC可能参与肿瘤细胞内钙恒稳的变化过程,异搏定的作用可能与磷脂酰肌醇信号传导系统相关。     

钙离子在激动剂引起豚鼠胆囊肌条收缩中的作用

本工作采用肌肉等张收缩记录法和 cGMP、cAMP 的放射免疫测定法,来研究乙酰胆碱、碳酰胆碱和胃肠激素(雨蛙肽)引起豚鼠胆囊肌条(GBMS)收缩中 Ca~(2+)的作用。结果表明,在有钙液中 GBMS 收缩较无钙液中强。在无钙液、在 EDTA-零钙液或异搏定-Krebs液中,GBMS 对激动剂的收缩反应降低到对照组的30%左右(P<0.01)。异搏定使碳酰胆碱刺激的 GBMS 内 cGMP 和 CAMP 含量降低(P<0.01或0.05)。这些结果提示,在激动剂引起胆囊肌条收缩中,细胞内、外钙离子均参与作用,从而影响胆囊肌条收缩。     

热应激时大鼠肺组织中β-肾上腺素受体的变化与膜磷脂代谢的关系

本文观察了热应激对大鼠肺组织细胞膜中β-受体Bmax,磷脂酶A_2(PLA_2)活性,磷脂酰胆碱(PC),磷脂酰丝氨酸(PS)含量的影响及膜流动性的改变。测得正常大鼠肺中β-受体的B_(max),PLA_2活性,PC和PS值分别为479±94fmol/mg蛋白,78.5±8.2U,53.5±9.7mg/g湿重和425.1±68.1μg/g湿重;在热应激使肛温达42℃并持续15min时,β-受体B_(max)减少43％;PLA_2活性增加83％,PC和PS分别减少50％和47％;测流动性结果表明,热应激使红细胞和肺组织细胞膜流动性都明显减弱。作者认为这些变化之间的关系是:β-受体B_(max)的减少可能是热应激时激活了肺组织细胞膜中的PLA_2,加速了PC和PS等的分解代谢,使膜液晶态改变的结果。     

SULFATE METABOLISM IN PANCREATIC ACINAR CELLS

The metabolism of inorganic sulfate in pancreatic acinar cells was studied by electron microscope radioautography in mice injected with sulfate-³⁵S. Labeled sulfate was concentrated in the Golgi complex at 10 min. Within 30 min, much of the radioactive material had been transferred to condensing vacuoles. These were subsequently transformed into zymogen granules. By 4 hr after injection, some of the zymogen granules with radioactive contents were undergoing secretion, and labeled material was present in the pancreatic duct system. The Golgi complex in pancreatic acinar cells is known to be responsible for concentrating and packaging digestive enzymes delivered to it from the endoplasmic reticulum. Our work demonstrates that the Golgi complex in these cells is also engaged in the manufacture of sulfated materials, probably sulfated mucopolysaccharides, which are packaged along with the enzymes in zymogen granules and released with them into the pancreatic secretion.     

牛胰多肽对大鼠胰腺外分泌细胞膜流动性的影响

胰多肽为含有36个氨基酸残基的直链多肽,是70年代后期发现的一种胃肠激素.本工作用荧光偏振法观察到,牛磺胆酸钠降低胰腺外分泌细胞膜的平均微粘度,而牛胰多肽能抑制牛磺胆酸钠的这一作用.结果提示,牛胰多肽有稳定胰腺外分泌细胞膜流动性的功能.     

CHANGES IN PANCREATIC ACINAR CELLS DURING PROTEIN DEPRIVATION

After 10 days of a protein-free diet the acinar cells of the rat pancreas showed a coarsening of nuclear matrix, depletion of zymogen granules, some loss of ribosomes, and a widening of the spaces between ergastoplasmic membranes. In addition, there could be found, but rarely, a lesion of the ergastoplasm consisting of vacuoles of agranular, disoriented membranes, which was similar to a lesion produced by ethionine. Thereafter, a return toward normal structure occurred which was characterized by beginning increase in the size of the Golgi apparatus at 12 days, appearance of zymogen granules at 18 days, and a relatively normal appearing but smaller cell at 28 days. After 10 to 12 days of protein deprivation a reversal of many of the morphologic effects of protein deprivation was accompanied by a return toward normal of some pancreatic enzyme activities. Possibly this spontaneous return toward normal levels represented a raiding of protein stores, or it may have been an adaptive phenomenon.     

新生犊牛胰腺内分泌机能的某些特点

６头装有暂时性颈静脉血管瘘的黑白花品种新生犊牛,在从出生至１５日龄的围产期内每天测定血浆葡萄糖（Ｇ）、胰岛素（Ｉｎｓ）和胰高血糖素（Ｇｃ）的基本浓度,可见１日龄喂初乳前Ｇ、Ｉｎｓ和Ｇｃ的浓度分别是１１９６．０±１５２．２ｍｇ／Ｌ、（７．３３±１．４３）×１Ｏ３Ｕ／Ｌ和６８５．３９±９５．４２ｎｇ／Ｌ。Ｇ于第２天明显下降,第３天回升,以后相对稳定;Ｉｎｓ第２天升高,以后下降,５日龄后相对稳定;Ｇｃ４日龄内逐日下降,５日龄后达到相对稳定水平。第１天喂初乳引起Ｉｎｓ显著升高,Ｇｃ下降,Ｇ无变化或者降低;以后喂初乳或常乳均引起Ｉｎｓ和Ｇ一致性升高,进食引起的Ｉｎｓ释放反应随日龄增长明显增加,Ｇｃ下降。不同日龄时灌注精氨酸均引起Ｉｎｓ显著增加,Ｇｃ早期无显著变化,７日龄后显著增加,同时Ｇ并无明显变化。灌注Ｇ引起Ｇ和Ｉｎｓ两者都增加,Ｇｃ下降。随日龄增长胰岛Ｂ细胞对精氨酸和Ｇ的反应明显加强。     

生长抑素在糖尿病大鼠胰腺外分泌功能降低中的作用

本实验观察到,用链佐霉素造成大鼠糖尿病模型,其胰腺组织中生长抑素含量明显升高。大鼠皮下注射生长抑素(100μg·kg~(-1)·d~(-1))5d,其胰腺组织中淀粉酶的含量明显降低。体外胰腺灌流也表明,生长抑素能抑制CCK—8刺激引起的胰腺淀粉酶释放。以上结果提示,糖尿病时胰腺组织中生长抑素含量的增加可能在胰腺外分泌功能降低中有一定的作用。     

糖尿病大鼠胰岛的一氧化氮合酶(NOS)与胰岛毛细血管三维结构的改变

以还原型辅酶Ⅱ黄递酶（ＮＡＤＰＨｄ）组织化学方法及扫描电镜（ＳＥＭ）,对正常组和糖尿病组大鼠胰岛的一氧化氮合酶（ＮＯＳ）与胰岛毛细血管的三维结构进行了观察。结果表现：正常组胰岛呈弥漫的蓝黑色ＮＯＳ阳性反应产物,但在糖尿病组胰岛的ＮＯＳ反应则明显减弱。ＳＥＭ显示正常组胰岛毛细血管蟠曲呈球状,且血管管径基本一致,而在糖尿病组胰岛中则可见部分毛细血管明显扩张。因此我们认为,糖尿病大鼠的胰岛毛细血管结构和功能均发生了改变。     

THE DEGENERATIVE CHANGES IN PANCREATIC ACINAR CELLS CAUSED BY DL-ETHIONINE

Degeneration of pancreatic acinar cells in rats injected with ethionine was studied by electron microscopy. The most conspicuous morphologic lesions occurred in the ergastoplasm. There was a widening of the endoplasmic reticulum, a decrease in number of membrane-associated ribosomes, and a development of fine and coarse vacuoles containing agranular disoriented membranes. Cytoplasmic ribosomes unassociated with membranes were less numerous. Nuclear changes consisted of a coarsening and clumping of the nuclear chromatin, chromatin margination, and increased osmiophilia and vacuolation of the nucleolus. Eight to ten days after the beginning of ethionine injections, changes in zymogen granules, mitochondria, and the Golgi apparatus appeared, but only after extensive damage to the acinar cell. The effects were consistent with ethionine's known interference with protein metabolism but also suggest disturbance in ribonucleic acid metabolism. The ergastoplasmic changes after ethionine were similar in some respects to the early lesions produced in liver parenchymal cells by fasting, to the changes occurring in animals on protein-free diets, or to some of the liver changes produced by azo dye carcinogens. The ribosomal and ergastoplasmic changes represent early morphologic expressions of the biochemical effect of ethionine.