北京医学院生理教研组研究工作情况简介

本教研組科學研究的總題目是:“消化与代謝的神經和體液性調節”。多數研究題目是在此範圍之內。此外,還又在進行燐脂類對於組織機能的影響、鈉鹽對於去神經的肌肉的敏感作用以及家兔和刺猬在麻醉和冬眠過程中的腦電變化等研究。茲分別將進行情况敍述如下:     

皮膚電刺激對胃分泌的抑制作用與神經型的關係

我們按小標準测定了實驗動物的神經型。基本上可將它們分成兩類:2只狗屬於强型;3只狗屬於弱型。在强型狗,皮膚電刺激對由組織胺所引起的胃液分泌有顯著的抑制作用,而在弱型狗則抑制作用不顯著。這些初步實驗結果說明,皮膚電刺激對胃液分泌抑制作用的個體差異与動物的神經型有着一定的關係。     

戊巴比妥鈉麻醉對於四氧嘧啶引起的初期血糖變化的影響

動物於注射四氧嘧啶(alloxan)後,產生初期高血糖和低血糖,最後形成永久性高血糖。一般認為初期高血糖的產生和腦下垂體,腎上腺及肝臟有關,低血糖係由胰島β細胞受損傷放出已形成的胰島素所引起。中樞神經機能活動的改變可以影響内外環境的各種動因對機體引起的反應,因此,中樞神經在戊巴比妥鈉麻醉下是否也能影響四氧嘧啶引起的初期血糖变化,是值得研究的。     

关於化學感受性反射後血壓的波浪性變化的問題

在以前的研究裏,我們曾觀察到在輕度麻醉的貓或狗,以游離腸段或後肢的灌注管中,注射適當劑量的二硝基酚、對硝基酚、乙酰胆鹼等藥物,反射地引起血壓升高和呼吸的變化。但在部分實驗中,每當血壓一度升高後,跟着出現一段時間的血壓的波浪性变化。當切斷四條緩衝神經,消除它們的抑制影響而使中樞神經系統處於興奮性提高的情况下,跟着化学感受性反射的增强,這種血壓的波浪性變化也相應地加大;與這一情况相反,如果在頸動脈寶内加壓而引起中樞抑制時,這種波浪性變化即减弱或者消失。 為了進一步瞭解這種波浪性變化產生的主要部位,我們繼續做以下兩组實驗。     

假飼對海登漢氏及畢克爾氏小胃分泌的影響

新近報告,切除幽門的神經支配後,海登漢氏小胃由進食引起的分泌的潛伏期延長3—4倍。用奴佛卡因封閉兩側頸部迷走神經後,觀察到海氏小胃由進食引起的分泌的潛伏期也延長。依Burstall和Schofield,如果切除主胃幽門,假飼不再使海氏小胃分泌增加,雖然在未切除前假飼曾引起分泌增加。但是Janowitz和Hollander在4只具有海氏小胃狗進行用胰島素和假飼刺激迷走神經的實驗,     

2,4-D对原生质粘度影响的初步观察

2,4-D以及其他植物刺激劑在農業生產上的應用已日趨廣泛起來,如防止落花落果、促進插枝生根、誘生無子果實、除莠打葉等等。同時正在研究它們在植物生理上的影響。按拉基金的說法,植物刺激劑所以能引起各種各樣的效應,只是在刺激劑通過植物本身的新陳代謝作用時,才有可能增强或抑制植物的生理功能與生長過程。所以刺激劑的作用不能理解成超越於有機體新陳代謝的特殊作用。由此,也不難理解刺激劑作用於植物體首先應該反映在它的生命部分。本文以各種不同濃度的2,4-D溶液處理植物表皮以测定溶液對原生質黏度的影響。由     

頸動脈竇加壓對清醒或淺麻醉動物呼吸運動的影響

在硫賁妥鈉淺麻醉下,或在清醒狀態下,犬的頸動脈竇用靜脈囊法加壓時引起呼吸運動的多樣性变化,主要是呼吸加强反應,呼吸抑制反應極少出現。呼吸加强乃由於壓力感受性神經衝動所引起,並非由於血壓降低或頸動脈體化學感受器受到刺激所引起的副作用。在清醒動物,重覆的頸動脈竇壓力刺激還可引起癫痫性發作,說明此種內感受性衝動能在中樞引起廣泛的興奮擴散。當切除或阻斷兩側迷走神經幹後,反應形式在基本上無变化,但少數實驗中呼吸抑制反應比較易於出現。看來呼吸中樞對頸動脈竇壓力感受性衝動的反應形式在極大程度上决定於中樞的機能狀態,但血管運動中樞對頸動脈竇壓力刺激的反應却不易变化。因此我們認為頸動脈竇壓力感受器在調節血壓方面起巨大作用,而對呼吸機能則僅發生影響而無直接的調節意義。     

輔酶細胞色素還原酶系的研究——Ⅰ.還原輔酶Ⅰ与琥珀酸的同時氧化

(一)本報告提供了一個從輔酶Ⅰ,用酶還原法製備還原輔酶Ⅰ的方法。我們所製得的還原輔酶Ⅰ鈉鹽乾粉,可以在低温保存數月而不被氧化。 (二)與心肌製劑中顆粒相結合的輔酶Ⅰ細胞色素還原酶系,和用乙醇抽出的水溶性的輔酶Ⅰ細胞色素還原酶的性質頗不相同。其中比較重要的不同點是對於細胞色素c的親力,前者遠大於後者,其米氏常數僅約為後者的十二分之一。 (三)用一心肌顆粒製劑作為材料,無論用氧或過量之細胞色素c作為氫受體,還原輔酶Ⅰ與琥珀酸同時氧化時的總速度,不等於二者分別氧化時速度之和,而僅等於其中氧化較快者單獨氧化時之速度。但如用[2,6]二氯靛酚作為氫受體時,二者共同氧化時之總速度完全等於二者分別氧化時速度的和。 (四)當用氧或過量之細胞色素c作為氫受體時,琥珀酸與還原輔酶Ⅰ能彼此互相抑制對方氧化的速度。有足夠的實驗材料說明,還原輔酶Ⅰ對於琥珀酸氧化的抑制,不是由於草醯乙酸聚集的緣故。 (五)如果在反應混合物中同時含有琥珀酸脫氫酶的專一抑制劑,丙二酸,則琥珀酸對於還原輔酶Ⅰ氧化作用的抑制即被解除。 (六)根據以上的實驗結果,可以認為,還原輔酶Ⅰ及琥珀酸先通過一個共同的因子與細胞色素c作用。這個共同的因子在一般情形之下,也是這兩個酶系統的速度限制因子。應該指出在我們的實驗中,並未使用任何可能影響酶系統結構的條件,因此我們的結果是在一個比較接近於生理狀態的情形之下獲得的。 (七)應該着重指出,從本報告的結果可以看到,一個用人為的方法從複雜酶系上溶解下來的酶的性質,有時並不能代表這個酶在有組織的酶系統中的真實情况。 (八)我們相信,本報告所說明的兩酶系競爭一個共同因子的一些現象,將为研究複雜酶系之間的相互關係,提供一個新的方法。     

常山鹼的药理

(一)本文報告常山鹼甲、乙、丙對於麻醉犬血壓、呼吸、聛腎容積、心收縮、在位小 腸與在位子宮的作用,並佐以它們對於離體心臟、小腸和子宮的作用觀察。三種常山鹼的藥理作用,在所用劑量時並無質的不同,亦無明顯的量的不同。和它們抗瘧作用的強弱懸殊,形成強烈的對此。 (二)對於麻醉犬,靜脈內注入2.5—10毫克/千克後,三種常山鹼都能降低血壓,呼吸無顯著變化。脾容積與腎容積多增加,心收縮則呈現振幅減小。 (三)離體兔心灌注時,從導管的側枝內注入0.2—2毫克常山鹼,能引起顯著的抑制,有時在抑制前可見輕微的興奮作用。對於離體蛙心,低濃度多產生興奮,高濃度則抑制之。 (四)對於麻醉犬的在位小腸,三種常山鹼在上述劑量時作用並不一致,有時興奮之,有時抑制之,對於子宮則多興奮之。 (五)對於離體兔腸與犬腸,常山鹼在所試劑量時,恆引起抑制。對於豚鼠空腸,則低濃度時抑制,高濃度時往往興奮之,或在短暫的抑制後繼以興奮。 (六)對於離體子宮的作用更為複雜,對家兔未孕子宮,一般作用不著,有時輕微興奮之,有時在興奮前略呈抑制。對於有孕子宮則均興奮之。豚鼠未孕子宮對常山鹼的效應一般不顯著。對大白鼠未孕子宮多抑制之,對其有孕子宮則多呈興奮作用。曾試常山鹼甲、乙於一猴的未孕子宫,均有興奮作用。     

我對發表“化學物質對植物器官形成的影響”一文的檢討

植物生長素的研究,最近二十年來頗有發展,我雖然在這方面也做了一些實驗工作,但是在觀點和思想方法上很不正確。1952年我在中國植物學報第1卷第2期發表“化學物質對植物器官形成的影響”一文,隨後經過同志們提出意見和自己的檢查,發見了許多錯誤,為了得到正確的解答,曾於1952年8月在上海中國科學院植物生理研究所舉行了一個“植物生長素”座談會,許多问志都說出了過去和现在對生長素的看法,我根據同志們的發言和自己經過學習後的認識,對那篇文章做一個初步的檢討。     

The effect of several neurotropic preparations on the differential character of pancreatic enzyme secretion]

Chronic experiments were conducted on dogs with pancreatic fistulae; secretion of the pancreas (basal and stimulated by duodenal perfusion by acid solutions, albumin and its polypeptide hydrolysate) was investigated with consideration to its enzyme (amylase, trypsin, chymotrypsin) secretion. The polypeptide hydrolysate proved to stimulate the pancreatic enzymes more than pure protein. Barbamyl, chlorpromazine and amyzyl inhibited both the basal and the stimulated secretion of the pancreas. The differential character of the pancreatic enzyme secretion was most disturbed by chlorpromazine and amizyl; this served as an evidence of the substantial role of the central adrenergic and cholinergic structures in the adaptation of the pancreatic secretion to food stimuli.     

Compensation of exocrine pancreatic insufficiency during its partial, subtotal and total resection

Chronic experiments on dogs have shown that the damage of extra-secretory pancreatic function by duct ligation caused marked compensatory changes of stomach function. The increase in gastric juice secretion and gastric juice proteolytic activity was accompanied by the reduction in its acidity. In addition to quantitative changes, qualitative shifts were revealed (amylolytic activity in strongly acid pH-reaction), never observed in the gastric juice of intact animals. Partial pancreas resection (up to 75%) both in control and test animals 10-14 months after pancreatic duct ligation was not accompanied by significant changes in gastric juice secretion. Total pancreas resection in dogs with previous pancreatic duct ligation caused neither prompt animal death, as in the control, nor the inhibition of compensatory reactions of gastric juice secretion.     

The effect of barbiturates on 24-h water intake and renal excretion of sodium and water in dogs

The effects of barbiturates on 24-h intakes of water and food and urinary excretion of sodium and potassium as well as on plasma concentration of sodium and potassium and osmolality were examined in dogs placed in metabolism cages and fed with a semiliquid diet. Administration of barbiturates stimulated drinking in a Series of 8 dogs having free access to water. Twenty four-h water intake and water balance increased significantly. Food intake, urinary output and urinary excretion of solutes, sodium and water did not change in this Series. A significant decrease in urine output as well as in osmolal clearance and urinary excretion of sodium was observed in a Series of 7 dogs having water restricted for 24 h following administration of barbiturates. Water balance increased in this Series. The same restriction of water in the dogs which had not received barbiturates did not modify renal excretion of water and electrolytes. Plasma osmolality, sodium and potassium concentrations did not change in either Series of experiments. It is concluded that barbiturates induce positive water balance either by stimulation of drinking when water is freely available or by reduction in urine output when water is restricted. The results suggest that expansion of the body fluids following the increased water intake may abolish reduction in urine output and sodium excretion which otherwise occur after administration of barbiturates.     

Corticotropin-releasing factor inhibits gastric emptying in dogs: Studies on its mechanism of action

The effects of corticotropin-releasing factor (CRF) on gastric emptying of a saline solution was further investigated in six dogs prepared with gastric fistulas and chronic cerebroventricular guides and in four other dogs with chronic gastric fistulas and pancreatic (Herrera) cannulas. Intravenous infusion of CRF significantly inhibited gastric emptying whereas intracerebroventricular injection of CRF had no effect. Pharmacologic blockade of β-adrenergic system by propranolol did not modify intravenous CRF induced delay in gastric emptying. Intravenous CRF did not influence basal pancreatic secretion whereas secretin infused stimulated bicarbonate secretion. These results indicate that intravenous but not intracerebroventricular administration of CRF inhibited gastric emptying of a saline solution in dogs. The inhibitory effect of intravenous CRF on gastric emptying is not mediated by the β-adrenergic nervous system, and not secondary to the release of other peptides that affect both pancreatic secretion and gastric emptying such as cholecystokinin and peptide YY.     

Reactive oxygen species stimulate insulin secretion in rat pancreatic islets: studies using mono-oleoyl-glycerol

Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca²⁺ or O₂ consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the K_ATP-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS.     

Effect of pancreatic polypeptide-antiserum on bombesin-stimulated pancreatic exocrine secretion in dogs

Bombesin is a potent stimulus of both pancreatic protein secretion and plasma pancreatic polypeptide (PP) release in dogs. Physiological plasma levels of PP have been shown to inhibit pancreatic exocrine secretion in dogs. We examined the question whether the concomitant release of PP exerts a suppressive action on the pancreatic exocrine response to bombesin in dogs by measuring pancreatic exocrine secretion with and without in vivo immunoneutralization of PP with a high affinity PP-antiserum. Bombesin was infused in a dose of 150 ng/kg·hr, resulting in a rise of plasma PP from 24±5 to 224±25 pM (p<0.01). Before this bombesin infusion, 7 ml of normal rabbit serum had been administered to the dogs (n=8). At a later stage, the study was repeated after administration of 7 ml of PP-antiserum to the same animals. The bombesin induced increase in pancreatic exocrine secretion during administration of PP-antiserum (flow rate 24±10 ml/hr, protein output 1.35±0.43 g/hr, and bicarbonate output 3.25±1.42 mmol/hr) was not significantly different from that during control rabbit serum (flow rate 21±7 ml/hr, protein output 1.26±0.38 g/hr, and bicarbonate output 3.18±1.10 mmol/hr). It is therefore concluded that the pancreatic exocrine response to bombesin is not affected by the concomitant secretion of PP.     

Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.     

吗啡和纳洛酮对酸化十二指肠引起狗胰液分泌的影响

本工作用制备 Thomas 胰瘘和胃痿的5条狗进行慢性实验。实验时用0.1N 盐酸灌入十二指肠以刺激胰液分泌,并分別注射吗啡或/和纳洛酮,观察它们对胰液分泌和对胰液中碳酸氢盐和蛋白质浓度的影响。另外我们还观察了吗啡和纳洛酮对6条狗离体胰主导管紧张性的影响。结果表明:(1)吗啡抑制了胰液分泌量,对胰液中碳酸氢盐和蛋白质浓度无影响,由于分泌量减少故两者的排出量显著减少(P<0.05),(2)纳洛酮本身对胰液分泌量和碳酸氢盐及蛋白质浓度均无影响;(3)纳洛酮可以加强吗啡抑制胰液分泌的作用(P<0.01);(4)吗啡能增加狗的离体胰主导管肌条的紧张性,纳洛酮不能阻断或翻转吗啡的这一效应,相反能加强其效应。本工作表明,吗啡抑制酸化十二指肠所引起的胰碳酸氢盐和蛋白质排出量,其机制可能是吗啡刺激胰导管收缩,而纳洛酮则加强吗啡的这种抑制效应。     

Effect of functional adrenalectomy on glucagon secretion and circulating catecholamines during insulin hypoglycemia in the dog

The present study was carried out to determine whether an increase in the pancreatic immunoreactive glucagon (IRG) secretion during the acute phase of insulin-induced hypoglycemia depends on circulating catecholamines of adrenal origin. Hypoglycemia was induced by a bolus insulin injection (0.15 IU/kg, i.v.) in dogs anesthetized with sodium pentobarbital (35 mg/kg, i.v.). Plasma aortic epinephrine (E) and norepinephrine (NE) concentrations increased significantly 30 min after the injection of insulin. At this time point, a functional adrenalectomy (diversion of bilateral adrenal venous blood from the systemic circulation) was performed for 5 min. The increased aortic E and NE concentrations significantly decreased reaching, within 5 min, a level below the corresponding preinjection control value. The basal output of pancreatic IRG (6.58 +/- 1.12 ng/min, n = 6) significantly increased (24.93 +/- 2.77 ng/min, p less than 0.05, n = 6) 30 min after insulin injection. During the functional adrenalectomy, the increased pancreatic IRG output diminished rapidly, within 5 min, to approximately 50% (11.73 +/- 3.19 ng/min, p less than 0.05, n = 6) of the value observed 30 min after insulin administration. In the other group of dogs receiving sham adrenalectomy, the increased aortic E and NE concentrations and pancreatic IRG output following insulin injection remained elevated above the levels observed immediately before the sham adrenalectomy. The net decrease in IRG output during the adrenalectomy was significant (p less than 0.05) compared with the corresponding net IRG output observed in the sham group.(ABSTRACT TRUNCATED AT 250 WORDS)