丹皮酚对心肌细胞自律性和延迟后除极的影响

目的与方法：采用常规玻璃微电极技术研究丹皮酚对离体心肌细胞自律性（ＡＭ）、延迟后除极（ＤＡＤ） 及触发活动（ＴＡ）的影响。结果：１．８×１０－４ｍｏｌ／Ｌ丹皮酚灌流组,肾上腺素（Ａｄｒ）的阈浓度空白对照组为（１．２８±０．５７）μｍｏｌ／Ｌ,药后为（１．５６±０．５３）μｍｏｌ／Ｌ（ｎ＝９,Ｐ＞０．０５）;用（１．８×１０－ ３） ｍｏｌ／Ｌ丹皮酚（Ｐａｅ）灌流组,Ａｄｒ 浓度由空白对照组的（１．２２ ±０．６２）μｍｏｌ／Ｌ升高到（６．２２±２．１１）μｍｏｌ／Ｌ（ｎ＝９,Ｐ＜０．０１）。１．８×１０－３ｍｏｌ／Ｌ的Ｐａｅ 能明显抑制哇巴因（Ｏｕａ）诱发的ＤＡＤ的幅值,当基本刺激周长为５００,４００,３００ 和２００ ｍｓ 时,其ＤＡＤ幅值从（５．５±２．０）ｍＶ,（７．３±２．１）ｍＶ,（８．０ ±２．４）ｍＶ和（９．２±１．９）ｍＶ减小到（３．０±１．１）ｍＶ、（３．６±１．７）ｍＶ,（４．３±２．０） ｍＶ和（５．９ ±１．６） ｍＶ,Ｐ＜０．０１。当基本刺激周长为２００ ｍｓ时,ＴＡ 数目由５．５±１．０ 降至０．７±０．３（Ｐ＜０．０１）。结论：丹皮酚能抑制心肌细胞ＡＭ、ＤＡＤ及ＴＡ,具有抗心律失常作用     

体外培养大鼠星形细胞的缺糖缺氧性损伤及药物的保护

本实验用大鼠星形细胞体外培养模型,观察了细胞在不同条件下乳酸脱氨酶（ＬＤＨ）的漏出。发现当去掉葡萄糖后,细胞缺氧５和７ｈ后ＬＤＨ漏出明显增加,５ｂ为５９．７±２５．３Ｕ／ｍｇ蛋白（对照组２４．７±１６．３,Ｐ＜０．０５）,７ｈ为６８．３±８９Ｕ／ｍｇ蛋白（对照组３９．９±２１２,Ｐ＜０．０１）。用３－氧－甲基－［１－￣３Ｈ］－Ｄ－葡萄糖摄取法测量细胞体积,结果显示缺糖缺氧５ｈ后细胞明显肿胀,从对照组的４．１±１．２增加到８．１±３．２μｌ／ｍｇ蛋白（Ｐ＜０．０１）。丹参有效成分７６４－３在０．５至５０μｍｏｌ／Ｌ时能减少缺糖缺氧细胞ＬＤＨ漏出;在５０μｍｏｌ／Ｌ时能减小缺糖缺氧细胞的体积。谷氨酸受体拮抗剂ＤＮＱＸ（６,７－ｄｉｎｉｔｒｏｑｕｉｎｏｘａｌｉｎｅ－２,３ｄｉｏｎｅ）５０μｍｏｌ／Ｌ能减轻星形细胞肿胀和ＬＤＨ漏出。     

α受体激动对绵羊心肌瞬时性内向离子流的影响

用乙酰毒毛旋花子甙元（ＡＳ）０．０５μｍｏｌ／Ｌ诱发绵羊心浦肯野纤维产生稳定的瞬时性内向离子流（Ｉｔｉ）,用普萘洛尔０．５μｍｏｌ／Ｌ阻断β受体,观察α受体激动剂苯肾上腺素（ＰＥ）０．３,１．０μｍｏｌ／Ｌ对Ｉｔｉ幅值与时程的影响。ＰＥ１．０μｍｏｌ／Ｌ灌流２０,５０ｍｉｎ时Ｉｔｉ幅值分别由对照值１２．８±１．９ｎＡ减小至１０．７±１．２ｎＡ（ｎ＝５,Ｐ＜０．０５）与９．６±１．９ｎＡ（ｎ＝５,Ｐ＜０．０１）;ＩｔｉＤ５０时程分别由对照值１４５±２４．４ｍｓ延长至１８３．３±２８．１ｍｓ（ｎ＝５,Ｐ＜０．０５）与２０７．５±３４．２ｍｓ（ｎ＝５,Ｐ＜０．０１）,ＰＥ对Ｉｔｉ的抑制作用呈剂量依赖性与时间依赖性。Ｉｔｉ到达峰值的时间和回复到基线的时间都延长,提示ＰＥ作用下Ｉｔｉ通道动力学发生了变化。如果在β受体激动剂异丙肾上腺素（ＩＳＯ）１．０μｍｏｌ／Ｌ增强Ｉｔｉ的基础上,ＰＥ１．０μｍｏｌ／Ｌ灌流１０ｍｉｎ,对Ｉｔｉ幅值的抑制及时程的延长作用更显著,Ｉｔｉ幅值由对照值１５．６±３．２ｎＡ减小到１０．３±２．２ｎＡ;ＩｔｉＤ５０由９２．５±１４．３ｍｓ延长到１３２．５±３６．０ｍｓ（ｎ＝５,Ｐ＜０．０１）。     

γ—氨基丁酸（GABA）对离体大鼠卵巢颗粒细胞孕酮分泌的影响

本文观察了ＧＡＢＡ对大鼠分散颗粒细胞生孕酮的影响。结果表明：当ＧＡＢＡ浓度为１０＾－＾６ｍｏｌ／Ｌ时明显促进颗粒细胞基础孕酮分泌（Ｐ＜０．０５）。但更高浓度（１０＾－＾５ｍｏｌ／Ｌ）时则表现抑制ＨＣＧ刺激孕酮生成的效应（Ｐ＜０．０２）。提示颗粒细胞的激素分泌功能可能受到ＧＡＢＡ的调控。     

内皮素和bFGF对MC的促增殖作用及胰岛素的协同效应

采用３Ｈ－ＴｄＲ参入法,测定碱性成纤维细胞生长因子（ｂＦＧＦ）、胰岛素和内皮素－１（ＥＴ－１）对体外培养的大鼠肾小球系膜细胞（ＭＣ）增殖的影响,以及胰岛素与ｂＦＧＦ或ＥＴ－１促ＭＣ增殖的协同作用。结果表明,不同浓度的ｂＦＧＦ（５－２００ｎｇ／ｍｌ）和胰岛素（０．１－２．４Ｕ／ｍｌ）均显著升高ＭＣ的３Ｈ－ＴｄＲ参入值（ｃｐｍ值）（Ｐ＜０．０１）。ＥＴ－１对ＭＣ的ｃｐｍ值的影响依剂量不同呈现两种不同的效应,在１０－９－１０－７ｍｏｌ／Ｌ时,随着浓度的升高,ＭＣ的ｃｐｍ值明显升高（Ｐ＜０．０１）,并以１０－８ｍｏｌ／Ｌ作用最强;当升高到１０－６ｍｏｌ／Ｌ时,ＭＣ的ｃｐｍ值出现降低趋势。胰岛素与ｂＦＧＦ或低浓度ＥＴ－１（≤１０－８ｍｏｌ／Ｌ）共同作用于ＭＣ时,ＭＣ的ｃｐｍ值明显高于二者单独作用之和（Ｐ＜０．０１）,与高浓度ＥＴ－１（＞１０－７ｍｏｌ／Ｌ）共同作用于ＭＣ时,ＭＣ的ｃｐｍ值小于二者单独作用之和（Ｐ＞０．０５）。上述结果说明,胰岛素、ｂＦＧＦ和ＥＴ－１均能显著促进ＭＣ增殖;胰岛素与ｂＦＧＦ或低浓度的ＥＴ－１促ＭＣ增殖具有正协同作用,与高浓度ＥＴ－１呈现负协同作用。     

过氧化氢和次黄嘌呤＋黄嘌呤氧化酶对家兔离体肺、脑动脉环缺氧反应的影响

在家兔离体肺内动脉、脑基底动脉环观察了过氧化氢（Ｈ２Ｏ２）及次黄嘌呤＋黄嘌呤氧化酶（ＨＸ＋ＸＯ）对动脉环缺氧反应的影响。结果发现：（１）Ｈ２Ｏ２１×１０－５ｍｏｌ／Ｌ加强ｆ去内皮肺动脉环（ＰＡ－）的缺氧收缩幅度（ＴＩＨ）,而Ｈ２Ｏ２３×１０－５ｍｏｌ／Ｌ、ＨＸ１０－４ｍｏｌ／Ｌ＋ＸＯ０．１及０．０３Ｕ／ｍｌ则可抑制内皮完整肺动脉环（ＰＡ＋）及ＰＡ－的ＴＩＨ（Ｐ＜０．０５）;（２）各剂量Ｈ２Ｏ２及ＨＸ＋ＸＯ对有、无内皮的脑基底动脉环的ＴＩＨ均无显著影响。     

表皮生长因子对离体大鼠肺动脉及肺动脉平滑肌细胞作用的研究

本研究着重探讨表皮生长因子（ＥＧＦ）对大鼠肺动脉的收缩作用及对肺动脉平滑肌细胞分裂增殖的影响。浓度为１×１０－９－１×１０－７ｍｏｌ／Ｌ的ＥＧＦ可引起大鼠肺动脉剂量依赖性收缩（ｒ＝０．９６８,Ｐ＜０,００１）,其Ｅｍａｘ为１００．６ｍｇ,ＥＣ５０为１１．９６ｎｍｏｌ／Ｌ。在同时存在０．５％胎牛血清（ＦＣＳ）时,ＥＧＦ能促进平滑肌细胞的３Ｈ－ＴｄＲ参入率,该作用与剂量呈正相关（ｒ＝０．８２３,Ｐ＜０．０５）,其ＥＣ５０为６．５×１Ｏ－１２ｍｏｌ／Ｌ。１×１０－９ｍｏｌ／Ｌ的ＥＧＦ＋０．５％ＦＣＳ能产生与１０％ＦＣＳ相当的促细胞分裂增殖能力（在培养的第１,３,５,７天,二者促分裂增殖能力相差不明显,Ｐ均＞０．０５,第９天时,前者大于后者,Ｐ＜０．０５）。１×１０－９ｍｏｌ／ＬＥＧＦ单独存在时对平滑肌细胞未显示出明显的致分裂活性。上述作用提示ＥＣＦ在某些肺血管病变如缺氧性肺动脉高压中可能有一定意义。     

运动对大鼠血小板L—精氨酸转运的影响

本工作在游泳大鼠模型上,观察血小板Ｌ－精氨酸（Ｌ－Ａｒｇ）转运特征,并观察凝血酶和ＰＡＦ对血小板Ｌ－Ａｒｇ转运的影响。结果发现,运动大鼠血小板Ｌ－Ａｒｇ转运明显高于未运动对照大鼠,表现在高亲和性最大转运速率（Ｖｍａｘ）明显增高（５０．５６±３．２７ｐｍｏｌ／１０８ｖｓ４５．８４±２．３６ｐｍｏｌ／１０８血小板／ｍｉｎ。Ｐ＜０．０５）,米氏常数亦显著增加（２．１４±０．２３μｍｏｌ／Ｌｖｓ１．４６±０．１３μｍｏｌ／Ｌ,Ｐ＜０．０１）。应用刺激剂凝血酶和ＰＡＦ诱导运动大鼠血小板Ｌ－Ａｒｇ转运速率增加的幅度明显高于未运动对照大鼠（Ｐ＜０．０１）。实验结果表明,运动能增强血小板转运Ｌ－Ａｒｇ的效率。提示,运动可能促进血小板一氧化氮（ＮＯ）生成,抑制血小板聚集,防治血管栓塞性疾病     

血小板生长因子(PDGF-BB)刺激体外培养兔肺动脉平滑肌细胞DNA和蛋白质合成

应用细胞培养、３Ｈ－ＴｄＲ和３Ｈ－Ｌｅｕｃｉｎｅ掺入方法,观察血小板生长因子ＢＢ（Ｐｌａｔｅｌｅｔ－ｄｅｒｉｖｅｄＧｒｏｗｔｈＦａｃｔｏｒＢＢ）对体外培养兔肺动脉平滑肌细胞ＤＮＡ和蛋白质合成的影响。结果表明：（１）当ＰＤＧＦ－ＢＢ浓度为１０ｎｇ／ｍｌ时,３Ｈ－ＴｄＲ掺入值已较对照组显著增高（６２６２．５±４１２．９ｖｓ８３３．５±１２４．０,Ｐ＜０．０５）;当ＰＤＧＦ－ＢＢ浓度为２０ｎｇ／ｍｌ时,３Ｈ－Ｌｅｕｃｉｎｅ掺入值亦较对照线显著增高（１０２１２．８±６３８．３ｖｓ７３４０．３±１１９７．９,Ｐ＜０．０５）。（２）ＰＤＧＦ－ＢＢ浓度在５－２５ｎｇ／ｍｌ范围内,３Ｈ－ＴｄＲ,３Ｈ－Ｌｅｕｃｉｎｅ掺入值与剂量直线相关（ｒＤＮＡ＝０．９７,ｒｐｒｏｔ＝０．９０Ｐ＜０．０５）。说明ＰＤＧＦ－ＢＢ刺激体外培养兔肺动脉平滑肌细胞ＤＮＡ和蛋白质合成。     

P物质对大鼠DRG神经元胞体膜的作用

本文在大鼠ＤＲＧ神经元标本上应用细胞内记录,以确定ＳＰ对ＤＲＧ细胞的膜反应及其可能的离子机制。实验所测ＤＲＧ细胞静息膜电位为－５８．９±８．２ｍＶ（Ｘ±ＳＥ,ｎ＝８１）。传导速度：Ａ_（α／β）细胞为２０．４±４．８ｍ／ｓ（Ｘ±ＳＥ）,范围１４．１－２８．７ｍ／ｓ（４７／６０）;Ａδ及Ｃ类细胞为９．８±５．２ｍ／ｓ,范围１．２－１３．７ｍ／ｓ（１３／６０）。浴槽滴加ＳＰ（１０￣（－７）－３×１０￣（－４）ｍｏｌ／Ｌ）在大多数细胞可引起明显的膜去极化反应（５６／６０）。少数细胞对ＳＰ无反应（４／６０）。在ＳＰ去极化期间膜电导值有所增加,从平均值２．７２×１０￣（－８）ｍｈｏ增加２４．６％（ｎ＝３）。所测逆转电位值在＋４０－＋５０ｍＶ之间（ｎ＝３）。浊流平衡液（ＢＳＳ）中ＮａＣｌ以氯化胆碱置代,或用含ＴＴＸ（１０￣（－５）ｍｏｌ／Ｌ）的ＢＳＳ灌流,可使ＳＰ－去极化幅值大大减小但不能完全消除。而高（２０ｍｍｏｌ／Ｌ）和低（０ｍｍｏｌ／Ｌ）Ｃａ￣（２＋）的ＢＳＳ灌流时,使ＳＰ－去极化幅值相应的增加和降低。用含１０￣（－４）ｍｏｌ／ＬＣｄ￣（２＋）及１０￣（－２）ｍｏｌ／ＬＴＥＡ的ＢＳＳ灌流,均使ＳＰ－去极化明显减小。     

血糖浓度对糖尿病大鼠胰腺外分泌功能的影响

用链佐霉素诱导大鼠产生尿病,其胰腺组织淀粉的含量降低,胆囊收缩素（ＣＣＫ－８）刺激所引起的胰淀粉酶分泌也明显降低。用一种可以降低糖尿病大鼠血糖,但不影响其血清胰岛素水平的药物－－钒酸钠灌胃,可翻转上述变化。体外实验分析表明,高糖可抑制胰腺泡蛋白质的合成,还可以引起胰腺泡膜丙二醛含量增加,从而提示,糖尿病大鼠胰外分泌功能障碍与血液葡萄浓度过高有密切关系。     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg^–1 I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7–8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg^–1 urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 ± 16.9 mg dl^–1, n= 6, prior to insulin and 42.0 ± 8.4 mg dl^–1, n= 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg^–1, I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 ± 14.0 mg dl^–1, n= 10, prior to insulin and 386.6 ± 43.6 mg dl^–1, n= 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation. (Mol Cell Biochem 261: 105–110, 2004)     

Fetal rat islet insulin deficiency following maternal administration of streptozotocin

Pancreatic islets were isolated from the fetuses of normal rats and rats made diabetic by the iv administration of streptozotocin (STZ) on either Day 3 or 5 of pregnancy. Of the rats made diabetic on Day 3, one group also received insulin injections at the appearance of glucosuria. Maternal blood glucose on Day 20 of gestation was significantly different in the diabetic rats (405 +/- 27 mg/dl) from the normal (97 +/- 1 mg/dl) and insulin-treated diabetic rats (69 +/- 9 mg/dl). While fetal weight was significantly decreased in the STZ-treated rats (2.64 +/- 0.13 g vs 3.52 +/- 0.05 g for the control group, P less than 0.005), fetal glucose was significantly higher in the STZ-treated than in normal pups (342 +/- 11 vs 35 +/- 1 mg/dl, P less than 0.005). Both fetal weight and glucose were normalized by insulin treatment: 3.16 +/- 0.18 g and 31 +/- 7 mg/dl, respectively. Insulin release from fetal islets of diabetic dams was blunted after a week in culture both in basal and stimulated conditions. After 2 weeks in culture, there was partial recovery in the insulin response to glucose but it did not equal to that measured in fetal islets from the normal and insulin-treated diabetic rats. These data suggest maternal hyperglycemia severely impairs fetal weight and insulin release from fetal rat islets in vitro, and correction of the hyperglycemia by insulin treatment not only improves fetal weight and glucose concentrations, but it also normalizes insulin release from fetal rat islets in vitro.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.     

Cholecystokinin-induced secretion and synthesis of amylase and cationic trypsinogen by pancreatic acini isolated from rats given an ethanol diet

Effects of chronic alcohol intake on secretion and synthesis of amylase and cationic trypsinogen (CT) were studied with pancreatic acini isolated from male Sprague-Dawley rats fed a Lieber-DeCarli ethanol or control diet for 30 days. Pancreatic acini were incubated in a media containing increasing concentrations of cholecystokinin octapeptide (CCK-8: 0-1000pM) followed by addition of [3H]leucine. Amylase and CT secreted in the media and those labeled in acini were quantitated. Basal and CCK-stimulated secretion of CT was not different in alcoholic and control groups. On the other hand, a dose-response curve of CCK-stimulated amylase secretion from alcoholic acini was markedly reduced with both basal and maximal secretion decreased to only 40% of controls. Basal incorporation of [3H]leucine into amylase was reduced by 70% in alcoholic acini compared to controls while that into CT was not different in the two groups. CCK-8 exhibited a biphasic effect on [3H]leucine incorporation into both enzymes in alcoholic acini: low concentrations of CCK-8 (less than 100pM) increased the incorporation whereas high concentrations (greater than 100pM) decreased it. However, in control acini, CCK-8 induced progressive suppression of the incorporation into these enzymes, the pattern of which was similar to that previously observed in fasted rats (Am. J. Physiol. 241:G116-G112, 1981). This difference in the response pattern resulted in significantly higher rates of CCK-8 induced incorporation into CT in alcoholic acini. These results suggest that the differences observed may possibly be attributable not only to alcohol intake but also to the differences in carbohydrate intake and in temporal patterns of diet consumption.     

Influence of B-cell impairment on pancreatic acini in NOD mice and streptozotocin-induced diabetic rats

Exocrine pancreatic function insufficiency, even of short duration, has been reported in juvenile-onset insulin dependent diabetic patients. To evaluate the status of pancreatic acini under decreased B-cell function, tissue insulin, amylase, chymotrypsinogen and trypsinogen in the pancreas were measured in streptozotocin-induced diabetic rats and non-obese diabetic mice in various conditions. In streptozotocin diabetic rats, a dissociation of three enzyme contents was demonstrated in the condition with discontinuation of insulin injection, i.e., a marked decrease in amylase, a significant increase in chymotrypsinogen, but no significant change in trypsinogen. This dissociation was markedly improved in the insulin-treated condition. In non-obese diabetic mice, these enzyme contents were not significantly changed although severe insulitis together with the marked decrease in insulin content was observed. These data show that the cessation of B-cell function alone does not cause insufficiency of exocrine pancreas.     

链脲佐菌素诱导糖尿病大鼠胰腺外分泌部A、B细胞密度的变化

本文应用A蛋白金银—过氧化物酶抗过氧化物酶(PAGS-PAP)双重染色法,观察了链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠胰腺外分泌部含高血糖素的单个A细胞(单A细胞)及合胰岛素的单个B细胞(单B细胞)密度的变化.在一次大剂量腹腔注射STZ后第5天和第10天,大鼠胰腺外分泌部单A细胞密度较对照组大鼠增加,而单B细胞密度在注射STZ后第5天较对照组大鼠减少,但在第15天与对照组大鼠接近.在第15天,一些单B细胞分布在靠近胰岛的腺泡中,岛周腺泡含单B细胞的胰岛百分率明显高于对照组.由于胰腺外分泌部的单A、单B细胞在分布特征上与中间细胞相似,在糖尿病时其数量变化也与中间细胞一致,因此,本研究所观察到的单A、单B细胞与前人报道的中间细胞有密切关系.上述单A、单B细胞密度的变化提示,在STZ诱导的糖尿病大鼠,胰腺中的B细胞被STZ破坏后,其外分泌部可能有某些细胞通过中间细胞向单A、单B细胞发生了转化或者单A、单B细胞即此转化过程中的中间细胞.     

The effects of quercetin on bone minerals, biomechanical behavior, and structure in streptozotocin-induced diabetic rats

This study was designed to investigate the effect of quercetin (QE) on bone minerals and biomechanics in insulin-dependent diabetic rats. Diabetes was induced by 50 mg kg(-1) intraperitoneal streptozotocin (STZ) in a single dose. The rats were randomly allotted into four experimental groups: A (control), B (non-diabetic + QE), C (diabetic), and D (diabetic + QE) each containing 10 animals. The diabetic rats received QE (15 mg kg(-1) day(-1)) for 4 weeks following 8 weeks of STZ injection. Blood samples were taken to determine glucose, insulin, calcium, and magnesium levels. The rats' femora were assessed biomechanically at femoral mid-diaphysis and neck. It was found that QE treatment increased insulin, calcium, and magnesium levels. Three-point bending of the femoral mid-diaphysis and necks showed significantly lower maximum load values (F max) in animals in the STZ group than the QE + STZ or control groups (p < 0.05). The results support the conclusion that QE treatment may decrease blood glucose and increase plasma insulin, calcium, and magnesium. QE treatment may also be effective in bone mineral metabolism, biomechanical strength, and bone structure in STZ-induced diabetic rats.     

Abnormalities of caerulein- and carbamylcholine-stimulated pancreatic enzyme secretion in the obese Zucker rat

The secretory function of the exocrine pancreas has been studied in dispersed pancreatic acini from obese and homozygous lean Zucker rats at 6 and 22 wk. No abnormality was found in acini from young rats. Acini from 22 wk obese and lean rats were equally responsive to secretagogues which stimulate cAMP, i.e. vasoactive intestinal peptide (VIP) and secretin. By contrast, there was a reduction in the maximum responsiveness to caerulein and carbamylcholine in acini from obese rats. These latter secretagogues act through mobilization of intracellular Ca2+. Since obese animals are insulin resistant and amylase release is modulated by insulin, the role of insulin resistance in the secretory defect was then investigated. A group of 22 wk obese rats received treatment with Ciglitazone (a drug which reduces insulin resistance in obese laboratory animals) for 4 wk before the secretion study. Despite the expected reduction in insulin resistance there was no improvement of the secretory defect seen with caerulein and carbamylcholine stimulation. Thus, the secretory abnormality in the exocrine pancreas of adult obese Zucker rats does not appear to be directly associated with insulin resistance. Furthermore, the secretory defect is linked to those secretagogues which induce Ca2+-independent phosphoinositide hydrolysis and Ca2+ mobilization in the target cell.     

Effects of insulin perfusion and altered glucose concentrations on heart function in 3-day and 6-week diabetic rats

Diabetes is known to result in depression of myocardial function, whereas hearts from insulin-treated diabetic rats exhibit functional characteristics similar to controls. In the present study, we have studied the effect of insulin perfusion on cardiac performance of 3-day and 6-week streptozotocin (STZ) diabetic rats. Three days of diabetes did not result in depressed cardiac performance when the hearts were isolated and perfused in the working heart mode. Increasing the concentration of glucose from 5 to 10 mM in the perfusion fluid did not alter the function in either control or in diabetic rat hearts. However, when regular insulin or glucagon-free insulin (Humulin) (5 mU/mL) was included in the perfusion medium, the ventricular function of hearts from control rats was significantly enhanced, while diabetic myocardial function remained unaffected. When the study was repeated on hearts from 6-week diabetic animals, cardiac function of diabetic rats was significantly depressed as compared with controls. As in the 3-day study, contractility was not affected in either group by increasing glucose concentration in the perfusion medium. Again, inclusion of insulin in the medium enhanced cardiac contractility only in control hearts. These results suggest that diabetes results in a loss of myocardial sensitivity to insulin which seems to occur as early as 3 days after induction of diabetes with STZ. The study also demonstrates that the beneficial effects of in vivo insulin treatment on myocardial alterations induced by diabetes are not due to its direct myocardial effects.