实验性大鼠结核病模型的特点

目的　探讨感染了结核菌的Wistar大鼠的实验特点。方法 用标准人型结核菌株H₃₇Rv 0.01mg经尾静脉注入Wistar大鼠,6周后剖杀大鼠,观察肺、肝、脾组织大体病变及镜下特点,肺组织匀浆培养有无结核菌落生长。结果 实验组大鼠肺组织可见明显的结核病变,感染成功率100%,肝、脾组织无结核病变。结论 Wistar大鼠对结核菌敏感,可作为结核病实验的动物模型。     

血小板源生长因子对离体大鼠胸主动脉血管张力的影响

目的 :观察血小板源生长因子对主动脉血管环舒缩作用的影响。方法 :采用离体灌流SD大鼠胸主动脉血管环标本 ,观察不同浓度的血小板源生长因子 BB（PDGF BB）对大鼠胸主动脉血管环的舒缩作用的影响 ,并与去甲肾上腺素 （NE）作对比。结果 :PDGF BB对大鼠胸主动脉有明显的收缩作用 ,阈浓度为 2× 10 -10 mol/L ,且呈现出一种浓度依赖关系 ;与NE相比 ,PDGF BB对血管的收缩幅度低于NE ,但其收缩血管的活性高于NE。PDGF BB对去内皮的血管同样产生收缩作用 ,鱼精蛋白可抑制PDGF BB收缩大鼠的胸主动脉的作用。结论 :PDGF BB对大鼠胸主动脉有明显的收缩作用 ,且呈现出一种浓度依赖关系 ,其血管收缩作用为非内皮依赖性收缩作用 ,鱼精蛋白可抑制PDGF BB收缩血管的作用。     

The effect of vanadyl treatment on vascular responsiveness of streptozotocin-diabetic rats

Summary Vanadyl sulphate has been demonstrated to possess insulin-like effects in streptozotocin (STZ) diabetic rats, including the normalization of hyperglycaemia and the prevention of diabetes-induced cardiac dysfunction. However, the effectiveness of vanadyl sulphate on diabetes-related vascular aberrations has not been questioned. Hence, in the present work, we have specifically addressed the question of whether chronic oral vanadyl sulphate treatment has any beneficial effect on diabetes-induced changes in vascular reactivity. Male albino rats were injected with a single intravenous dose of STZ (55 mg/kg). Vanadyl sulphate was administered in the drinking water at a concentration of 1 mg/ml from 7 days after the STZ injection and treatment was maintained for 10 weeks. Vanadyl intake was accompanied by decreased blood glucose and serum insulin levels. The effects of diabetes on vascular smooth muscle function were assessed by the responsiveness of aortae to noradrenaline and KCl. Contractile responses of the diabetic aortae were found to be significantly increased as compared with controls. However, there were no significant differences in pD₂ values of the agonists in either of the groups. Treatment of diabetic rats with vanadyl sulphate completely prevented the increases in responsiveness of aortae to noradrenaline and KCl. The effect of diabetes on the fast and slow components of noradrenaline-induced contraction was also examined. Both components of the response to noradrenaline were significantly increased in diabetic aortae. These changes were also prevented by vanadyl sulphate treatment. The data demonstrate that 10-week vanadyl sulphate treatment results in improved vascular reactivity of diabetic rats.Abbrevations STZ streptozotocin - VST vanadyl sulphate trihydrate     

模拟失重大鼠胸主动脉平滑肌细胞凋亡的变化及间断性人工重力对抗的影响

目的:观察模拟失重大鼠胸主动脉平滑肌细胞凋亡的变化及间断性人工重力对其影响。方法: 将27只SD大鼠随机分为3组（每组9只）,即对照组(CON)、模拟失重组(SUS)及站立对抗组(STD)。以尾部悬吊大鼠模拟失重3周,同期每天悬吊23 h、站立1 h模拟间断性人工重力对抗的效果。用TUNEL染色法检测SUS组、同步对照(CON)组及STD组大鼠胸主动脉平滑肌细胞的凋亡情况;用Western blot法检测各组大鼠胸主动脉组织中Bad、FasL及Caspase-3蛋白表达的变化。结果: 与CON组比较,SUS组大鼠胸主动脉平滑肌细胞TUNEL染色阳性的细胞明显减少(P<0.01);STD组TUNEL染色阳性的细胞较CON组及SUS组显著增加（P<0.01）。SUS组Bad的表达较CON组和STD组显著减少（P<0.05）,STD组Bad的表达较CON组有增加的趋势,但无统计学差异。SUS组FasL及Caspase-3的表达较CON组显著降低(P<0.05);STD组FasL及Caspase-3的表达较CON组及SUS组显著增高(P<0.01)。结论: 模拟失重可减少大鼠胸主动脉平滑肌细胞凋亡,每日1 h的-Gx对抗可使胸主动脉平滑肌细胞的凋亡增加,提示血管组织平滑肌细胞的凋亡在失重引起的动脉血管适应性重构中可能发挥重要作用。     

甲状腺机能亢进大鼠腹主动脉与股动脉血管反应性的变化

目的观察甲状腺机能亢进时大鼠大动脉和中等动脉离体血管环收缩反应性和舒张反应性的变化,以探讨甲亢时动脉反应性变化对外周循环的影响。方法采用左旋甲状腺素（左旋T4,优甲乐）胃饲大鼠25 d建立甲亢大鼠模型。24只雄性SD大鼠（体质量350400 g）随机分为3组（每组8只）:对照组,甲亢1组[(低剂量组,左旋T4,0.3 mg/（kg.d）],甲亢2组[(高剂量组,左旋T4,0.6 mg/（kg.d）],使用离体动脉环测定腹主动脉和股动脉血管的反应性。结果甲亢组和对照组相比,由氯化钾（19）×10-2mol/L和苯肾上腺素（10-9mol/L10-4mol/L）激发的两种动脉血管的收缩反应显著降低（P<0.05）;由乙酰胆碱（10-9mol/L10-4mol/L）和硝普钠（10-9mol/L10-4mol/L）引起的舒张反应则显著增强（P<0.05）。甲亢组大鼠的腹主动脉与股动脉对氯化钾、乙酰胆碱和硝普钠反应的敏感性增强,而对苯肾上腺素反应的敏感性减弱。结论甲亢大鼠腹主动脉和股动脉的血管收缩反应性降低,而舒张反应性增强。     

Effects of nesfatin-1 on atrial contractility and thoracic aorta reactivity in male rats

Background: This study aimed to examine the effects of nesfatin-1 on thoracic aorta vasoreactivity and to investigate the inotropic and chronotropic effects of nesfatin-1 on the spontaneous contractions of the isolated rat atria.

Methods: Isolated right atria and thoracic aorta were used in organ baths. The reactivity of the thoracic aorta was evaluated by potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP). The effects of nesfatin-1 on the spontaneous contractions of the rat atria were also examined.

Results: Nesfatin-1 (0.1–100 ng/ml) produced a concentration-dependent relaxation response in rat thoracic aorta. The relaxant responses to nesfatin-1 were inhibited by the removal of endothelium, NO synthase blocker N-nitro-L-arginine methyl ester (L-NAME, 10^?4 M), and soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10^–5 M). Nesfatin-1 (10 ng/ml, 30 min) increased the relaxation responses to either ACh or SNP, and the contractile response to both Phe and KCl did not significantly change in the arteries that were incubated with nesfatin-1 compared with the controls. The thoracic aorta contractions induced by the stepwise addition of Ca²⁺ to a high KCl solution with no Ca²⁺ were not significantly changed by nesfatin-1. Under calcium-free conditions, the contractions of the thoracic aorta rings incubated with nesfatin-1 in response to Phe were not significantly lower than those of the rings from the control rats. Nesfatin-1 showed positive inotropic and chronotropic effects on rat atria.

Conclusion: Nesfatin-1 significantly changed the vascular responsiveness in rat thoracic aorta and produced positive inotropic and chronotropic effects on rat atria.     

肠内生态营养对创伤后大鼠肠屏障功能的影响

目的:研究肠内生态营养对创伤后大鼠肠道屏障功能的影响.方法:将30只Wistar大鼠随机分为3组,即对照组、普通肠内营养组和肠内生态营养组.胃造瘘术后分别给予普通饲料、肠内营养剂和肠内生态营养剂7 d,检测小肠黏膜形态学参数和黏膜IgA ,CD3 ,CD4 和CD8 细胞数量.结果:肠内生态营养组的小肠绒毛高度(205.4 μmvs 177.7 μm,P＜0.05)、肠腺隐窝深度(99.4 μmvs 77.7 μm,P＜0.05)、黏膜厚度(299.9μm vs 267.0 μm,P＜0.05)以及绒毛表面积(10 321.5μm2 vs 8927.6 μm2,P＜0.05)均高于对照组,肠内生态营养组和普通肠内营养组比较差异无显著性(P＞0.05).肠内生态营养组大鼠小肠黏膜中IgA 细胞(21.2 vs 17.5,19.4,P＜0.05)和CD3 (24.2 vs 20.2,22.1,P＜0.05),CD4 (13.4vs 8.9,11.0,P＜0.05)、CD8 (18.7 vs 12.6,15.4,P＜0.05)细胞数均高于对照组和普通肠内营养组.结论:肠内生态营养能较好的改善创伤后大鼠的小肠机械屏障功能,促进小肠黏膜屏障功能的恢复,增强其肠道免疫功能.     

碘过量对大鼠仔鼠垂体促甲状腺激素细胞的影响

目的探讨碘过量对仔鼠垂体TSH细胞的影响。方法将断乳1个月的W istar大鼠,雌雄各半随机分为4组:NI组、10H I组、50H I组和100H I。饲养3个月的雌雄大鼠1∶1合笼交配产生仔鼠,断乳后的仔鼠喂养同上述大鼠。测定出生60日龄仔鼠的甲状腺和垂体的相对重量及垂体TSH细胞的体密度和面数密度。结果50H I组、100H I组仔鼠的体密度和面数密度明显高于NI组和10H I组,但垂体和甲状腺的相对重量与NI组相比无明显变化。结论50H I组、100H I组不会引起仔鼠甲状腺肿,甲状腺对碘过量有较强的适应性和耐受性。     

金雀异黄素对大鼠胸主动脉舒张功能的影响及其机制

目的观察植物雌激素金雀异黄素(genistein,GST)的快速舒张血管效应,并探讨其作用机制。方法选择雌性SD大鼠30只,取胸主动脉后,每条制成4个血管环(共120个血管环),采用血管张力仪进行体外血管灌注实验,测量不同浓度GST和17β-雌二醇(E2)大鼠体外胸主动脉环等长张力;另将血管按不同实验分为4组:对照组、左旋硝精氨酸甲酯(L-NAME)组、他莫昔芬(TAM)组和过氧化物酶体增殖物激活受体γ(PPARγ)组,并测量各组血管环张力。结果不同浓度GST(10-9~10-6mol/L)对苯肾上腺素(10-6mol/L)预收缩的血管环能产生浓度依赖性快速舒张血管效应,其作用与E2相似。与对照组比较,L-NAME组、TAM组、PPARγ组均能抑制GST的舒张血管效应。结论GST的快速舒张血管效应主要与内皮释放的NO有关,部分与PPARγ的调节作用有关,并通过雌激素受体发挥作用。     

Effects of nonsteroidal,antiinflammatory drugs on gastrointestinal injury and prostanoid generation in healthy volunteers

A new nonsteroidal, antiinflammatory drug, carprofen, was compared with indomethacin as to their effects on mucosal injury and prostanoid biosynthesis. A prospective, double-blind endoscopy study was performed in 40 healthy adults. After baseline normal endoscopy, 20 subjects were randomly assigned to either indomethacin (25 mg four timesdaily) or carprofen (150 mg twice daily) for eight days and reendoscoped. Urinary and gastric mucosal prostaglandin generation, respectively, of PGE₂ and PGE₂, and PGE and 6-keto-PGE₁ was determined. Minor subjective symptoms occurred in six of 20 indomethacin (including four of eight with gastrointestinal injury) and in three of 20 carprofen subjects. Indomethacin and carprofen reduced gastric and urinary prostaglandin synthesis to a similar degree. Gastrointestinal injury was present in eight of20 indomethacin and in none of 20 carprofen subjects. This study fails to establish a relationship between duodenal mucosal lesions and gastric prostanoid generation and confirms the lack of correlation between indomethacin-induced duodenal injury and subjective symptomatology. Carprofen appears to produceless objective damage in the upper gastrointestinal tract than indomethacin at comparable clinical doses.This study was supported in part by a grant from Hoffman-La Roche Inc., Nutley, New Jersey. Portions of these studies were presented at 87th Meeting of the American Gastroenterological Association at San Francisco, California, on May 20, 1986. A preliminary report of this work has been published in abstract form (Gastroenterology 90:1520, 1986).     

Wistar大鼠血象及生化指标正常值初步观察

为建立本实验室 Wistar大鼠血象和生化指标的正常值范围并为制定全国统一标准提供参考依据 ,选用普通级Wistar大鼠 (雄性 10 2只体重为 112± 2 7g,雌性 10 1只体重为 10 7± 2 6 g) ,普通采血 ,测定了血象和血清生化指标 ,对测定结果进行了讨论并分析了性别差异     

Effect of losartan on angiotensin II-mediated endothelin and prostanoid excretion in humans

Angiotensin II (Ang II) stimulates renal prostanoid and vascular endothelin-1 (ET-1) release. Most known Ang II effects are mediated by AT₁ receptors. Our aim was to determine whether AT₁ receptor activation mediates Ang II-evoked renal prostanoid and ET-1 release. Eleven healthy men were randomized in a crossover, double-blind fashion to receive 100 mg/day of losartan or matching placebo, for 8 days. Blood and urine were sampled before and after a 2-h infusion of Ang II at a rate previously determined to increase mean arterial pressure (MAP) by 25 to 30 mm Hg in each subject. After a 14-day washout, subjects received the alternate treatment. Pretreatment with losartan had little effect on baseline MAP, but increased plasma renin activity, and virtually eliminated the pressor response to Ang II infusion. Angiotensin II significantly increased prostanoid excretion after placebo; the prostanoid response to Ang II was even greater after losartan. Plasma ET-1 was not altered by Ang II infusion, with or without losartan. In contrast, urine ET-1 excretion rate decreased to 40% of baseline after Ang II but not after losartan pretreatment; losartan alone had no effect. We conclude that Ang II decreases renal ET-1 synthesis and release through the AT₁ receptor. In contrast, Angiotensin II-mediated renal prostanoid synthesis does not require activation of AT₁ receptors. These findings indicate that AT₁ receptor antagonists could provide renal protection through indirect mechanisms.     

缬沙坦对腹主动脉缩窄大鼠心血管重构的影响

目的观察血管紧张素Ⅱ1型受体拮抗剂缬沙坦对腹主动脉缩窄(AAC)大鼠心血管重构的影响。方法用AAC法建立动物模型,将32只雄性SD大鼠随机分成4组:假手术组,AAC对照组,AAC低剂量缬沙坦组(1mg·kg-1·d-1),AAC高剂量缬沙坦组(30mg·kg-1·d-1),每组8只。药物经灌胃6周后通过颈动脉测定收缩压,同时测定左心室重量指数。用图像分析仪检测出主动脉和肠系膜上动脉中膜厚度/管腔内径比值。用放射免疫法测定血浆及心血管中的血管紧张素Ⅱ、醛固酮。结果无显著降压作用的低剂量缬沙坦能抑制主动脉、肠系膜上动脉中膜肥厚及左心室肥厚,但明显降低血压的高剂量作用更显著,AAC高剂量缬沙坦组上述各项参数与假手术组无显著性差异。结论缬沙坦能抑制AAC大鼠心血管重构,其可能机制是与抑制了心血管局部肾素-血管紧张素-醛固酮系统的活性有关。     

Pioglitazone time-dependently reduces tumour necrosis factor-α level in muscle and improves metabolic abnormalities in Wistar fatty rats

Summary In order to evaluate the relationship between tumour necrosis factor-α (TNF-α) level in muscle and metabolic abnormalities in obesity and diabetes mellitus, pioglitazone, a novel insulin-sensitizing agent, was administered to Wistar fatty rats and time-dependent changes in muscle TNF-α content and plasma indicators of diabetes and obesity were measured. Wistar fatty rats were hyperglycaemic, hyperlipidaemic and hyperinsulinaemic, and their plasma and muscle TNF-α levels were two or more times higher than those in normal lean rats at 16 weeks of age. When pioglitazone was administered to fatty rats at a dose of 3 mg · kg^–1· day^–1, the plasma triglyceride level and TNF-α levels in plasma and muscle decreased time-dependently, and reached the levels of lean rats within 4 days. Plasma glucose and insulin levels also decreased time-dependently with pioglitazone, but on day 4, these levels were still much higher than the levels in lean rats. Neutral sphingomyelinase (SMase) activity in muscle of fatty rats was two times higher than that in lean rats and was lowered to the level of that in lean rats by 4 days' pioglitazone administration. The plasma leptin level in fatty rats was 8 times higher than that in lean rats, but pioglitazone did not affect the level during the 4-day administration period. These results suggest that an increase in TNF-α production and subsequent activation of SMase in muscle leads to metabolic abnormalities in obesity and diabetes and that antidiabetic activity of pioglitazone is deeply associated with the suppression of TNF-α production. [Diabetologia (1998) 41: 257–264] Received: 29 August 1997 and in revised form: 13 October 1997     

Contractions to Endothelin in Normotensive and Spontaneously Hypertensive Rats: Role of Endothelium and Prostaglandins

Contractions to endothelin-1 in aortas of the spontaneously hypertensive rats (SHR) were compared with those of normotensive controls (WKY); rings with and without endothelium were studied in organ chambers. Contractions to endothelin were smaller in aortas of SHR compared to WKY, whether the endothelium was present or not. The presence of a functional endothelium reduced contractions to the peptide in both strains. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to nitric oxide were observed in rings from both strains during contraction with endothelin. Indomethacin reduced the contractions to endothelin in the aorta from SHR with endothelium, but not in those without endothelium; it did not significantly affect endothelin-induced contractions in rings of WKY with or without endothelium. These experiments demonstrate that contractions of the vascular smooth muscle to endothelin are reduced in the aorta of the SHR. The basal and stimulated release of endothelium-derived relaxing factor inhibits contractions to endothelin in the aorta from both strains. The inhibitor of cyclooxygenase indomethacin does not prevent the response of the vascular smooth muscle to endothelin; however, endothelin may stimulate the release of an indomethacin-sensitive endothelium-derived contracting factor in the SHR aorta.     

氟砷联合染毒对Wistar大鼠子代皮毛影响的研究

为探讨氟砷联合作用对动物皮毛的影响,我们采用了两代一窝繁殖试验,观察亲代动物接触氟砷后子代皮毛中砷含量的变化,并用扫描电镜观察其超微结构的变化,结果显示：皮毛中砷含量随染毒剂量的增加而增加,扫描电镜观察发现毛小皮出现明显的病理变化,主要表现为毛小皮的破损和赘生物的形成,但两代子代之间这些变化没有明显差异,这说明氟砷可使动物皮毛发生明显的变化,其作用机制有待进一步研究。     

饲料中蛋白质水平对Wistar大鼠体重影响观察

为观察饲料中蛋白质水平对Wistar大鼠生长的影响,分别饲喂含蛋白质31．2％、23．8％和16．1％的饲料,观察大鼠体重的变化,三组Wistar大鼠体重增长有差异（P＜0．05）。雌雄间体重有极显差异（P＜0．01）。     

Sulindac and indomethacin inhibit formation of aberrant crypt foci in the colons of dimethyl hydrazine treated rats

Aberrant crypt foci are microscopic lesions found in the colons of rodents treated with carcinogens, and in patients with premalignant colorectal conditions. They consist of single or multiple abnormal crypts and show cellular changes ranging from dysplasia to microscopic adenomacarcinoma. It is thought that these lesions represent the initial stages of the adenomacarcinoma path that results in the development of colorectal neoplasia. We have examined the effect of sulindac and indomethacin on the formation of aberrant crypt foci in rats treated with dimethylhydrazine (DMH). Aberrant crypt foci were induced in male Sprague-Dawley rats with two oral doses of dimethyl hydrazine at 25 mg/kg per dose. Rats were randomized to receive sulindac at 3 mg/kg (n= 20) or 10 mg/kg (n=18) b.d., indomethacin at 1 mg/kg per day (n=18) or 2 mg/kg per day (n=19) or control (n= 37). Drug treatment was started on the day following the first dose of carcinogen and continued for 3 weeks. Colons were fixed flat overnight in 10% formalin and stained with 0.2% Methylene Blue solution before being studied. There was a significant reduction in the number of aberrant crypt foci in rats treated with 10 mg/kg b.d. sulindac (P= 0.001) and indomethacin at 2 mg/kg per day (P= 0.0002). Sulindac, at 3 mg/kg b.d., and indomethacin, at 1 mg/kg per day, did not have a statistically significant effect (P= 0.089 and P= 0.052, respectively). None of the drug treatments affected the relative frequency of single crypt vs multiple crypt foci. Previous studies have shown that sulindac and indomethacin will significantly inhibit the growth and development of tumours in DMH treated rats. The current data suggest that one of the pathways of action of NSAID is to inhibit the formation of early preneoplastic lesions.