瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体mRNA表达的影响

目的研究瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体(Ob-R)mRNA表达的影响。方法采用六孔板培养皿培养鼠平滑肌细胞,5个孔作为一个浓度组,通过半定量的RT-PCR方法,分别观察了不同浓度的大鼠瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体mRNA表达水平的影响。结果通过半定量RT-PCR,我们检测了短型瘦素受体(Ob-Ra)和长型瘦素受体(Ob-Rb)的mRNA表达水平,瘦素受体(Ob-R)mRNA表达水平随着瘦素及IL-6浓度增加而上升,随着胰岛素的浓度增加而下降。结论瘦素及IL-6可在体外上调平滑肌细胞瘦素受体的表达,胰岛素可下调平滑肌细胞瘦素受体的表达。这三个因子参与了瘦素受体的表达调控,对我们了解瘦素抵抗的发生机制有重要意义。     

大鼠心脏的雌激素受体免疫组织化学研究

观察雌激素受体在雌性与雄性大鼠心脏中的表达.取大鼠心房与心室组织制作冰冻切片,应用抗雌激素受体单抗进行免疫组织化学(SP法)染色并进行图像分析.结果显示,雌性与雄性大鼠心脏都存在雌激素受体,且受体的表达无性别差异(P＞0.05);心房与心室都存在雌激素受体阳性表达,其表达也无明显差异(P＞0.05);阳性反应见于心肌细胞和成纤维细胞.结果表明,大鼠心脏存在雌激素受体,心房与心室都可能是雌激素的靶组织;心血管疾病的性别差异与雌性、雄性的受体含量无关,可能与生理条件下受体的活性及功能状态有关.     

ON THE MECHANISM OF MILK SECRETION : THE INFLUENCE OF INSULIN AND PHLORIDZIN

The four types of experiments on milk secretion herein described really fall into one general class so far as the physiological effects produced are concerned. Starvation lowers the blood sugar and raises the osmotic pressure of the blood. The experiment using parathyroid hormone with or without starvation may have its effects interpreted as simply due to starvation since 1000 units of this hormone produced no visible effects on the blood calcium or milk constituents different from those of starvation. Since insulin produces a marked and rapid drop in blood sugar it too may be looked upon as a rapid starvation effect. It has some other important effects, however. Briggs et al. (21) have shown that potassium and phosphorus of the blood are decreased and Luck, Morrison, and Wilbur (22) indicate a reduction in the amino acids of the blood in insulin treatment. Phloridzin lowers the threshold for sugar retention with the consequence that in time it tends to lower the sugar of the blood to an even greater extent than that noted in starvation. It tends to depress the potassium, to increase the phosphorus content of the blood, and to cause the body to burn protein rather than carbohydrate, thus increasing nitrogen excretion. All of the experiments are characterized by a sharp reduction in the milk yield. Cary and Meigs (23) have studied like reductions in milk yield produced by varying the energy or protein of the diet. They conclude that such decrease in milk production may be interpreted as due to the direct effect of the starvation and the consequent reduction of the energy and protein available to milk secretion. The reduction in milk yield for the experiments herein described can undoubtedly be attributed to the same causes as those cited by Cary and Meigs. The experiment where Cow 47 was given a full ration and at the same time injected with large quantities of insulin is of particular interest in this connection. The ration was adequate and the cow ate well, yet her production declined to a fifth of her normal milk yield. Her chart shows that there was a slight reduction in her blood sugar when insulin was introduced into the blood stream. It seems furthermore likely that this sugar was not as available to milk secretion, since there appears to be more than a corresponding drop in the lactose content of the milk. The work of Luck et al. would seem to indicate that there should be a like drop in the amino acids of the blood. These two conditions would lead, according to the work of Cary and Meigs, to a reduction in the concentration of the nitrogen of the milk. Actually, in the experiment as it was performed, the nitrogen increased to a value about 40 per cent above normal. A somewhat similar conflict is noted in two of the other three insulin experiments where starvation accompanied insulin injection. To this extent it would seem that the factor deserving most emphasis in its immediate effect on milk yield is the energy available, and that the later and more secondary factor is the amino acid concentration of the blood. In the starvation experiments, the butter fat percentage of the milk rises rather uniformly with the duration of starvation. In the insulin experiments, however, the charts appear to show a marked reduction in this butter fat percentage immediately after the introduction of insulin. This is particularly noticed after the second and third injections. Since the dextrose of the blood tends to be reduced and made unavailable to the general physiological processes by the presence of the large excess of insulin, and since this reduction of the butter fat percentage is noted as an accompanying phenomenon, it would appear that the blood dextrose plays a part in the synthesis of milk fat as well as being the source of the milk lactose, possibly as a source of energy in converting body fat to butter fat. In this regard the results for the treatment of Cow 47 with phloridzin are of importance. As noted by others, the introduction of phloridzin causes a marked rise in the fat percentage of the milk. The lactose per cent is also higher than that noted in starvation. Since phloridzin, by lowering the threshold for the blood sugar, causes large quantities of it to be drained from the body through the urine, and therefore reduces the reserve supply, it follows that if the insulin hypotheses are correct we should expect an eventual lowering of the lactose and of the fat below the starvation level. During the last of the experiment this is what was actually observed. The effects of starvation and of insulin furnish concordant proof for the theory that the lactose of milk is derived from the sugar of the blood. The fact that the different constituents of the milk, the fat, the lactose, the nitrogen, and the ash, do not exactly parallel each other in their behavior throughout these experiments indicates that they have in all probability separate origin. This is particularly true of the butter fat percentage, which appears to have a rate of secretion which is more or less independent of the other constituents, and higher in amount. This result would fall in line with the conclusion of the writers in a previous paper in which it was indicated that the fat of the blood was very likely deposited in the udder as fat corresponding to body fat from which source it was metabolized into the fat of milk shortly before it was needed for milk secretion. The wide variation brought about in the constituents of the milk by the treatment all point to the conclusion that in milk secretion a balance is maintained between the osmotic pressure of the milk and of the blood. Thus when the sugar of the milk is reduced either through starvation or by insulin the ash constituents rise to compensate for this reduction and make the osmotic pressure of the milk similar to that of the blood. These results further appear to indicate that the salts and the sugars are more or less independent in their passage and metabolism into milk from the other constituents. These observations are therefore in line with those obtained by Jackson and Rothera (14) and by Davidson (15) in their brilliant experiments where they modified milk secretion by returning milk or milk sugars and salts to the udder. These experiments give direct proof for the conclusion that modifications of the blood of dairy cattle produce direct and predictable modification of the milk secreted.     

第三脑室注射组胺及其受体激动剂对五肽促胃液素诱导的大鼠胃酸分泌的影响

本文报道第三脑室注射组胺(0.25—2.0μg/5μl)对五肽促胃液素诱导的胃酸分泌的双重影响。雄性Wistar大鼠,重200—300g,戊巴比妥钠腹腔麻醉。用37℃生理盐水通过恒流泵进行连续胃灌流。在静脉恒速灌注五肽促胃液素(7.5μg/kg·h)的基础上,第三脑室注射组胺(0.25μg/5μl)或H_1受体激动剂2-Pyridylethylamine(PEA,10μg/5μl),10min后总酸排出量即开始减少,90min仍未恢复。组胺剂量增至1.0μg或2.0μg时,出现双重效应。部份动物(分别占73％或50％)胃酸分泌减少,另一部分动物(27％或50％)胃酸分泌增多。H_2受体激动剂dimaprit(10μg/5μl)或impromidine(0.1μg/5μl)对胃酸分泌无明显影响。苯海拉明(16μg/0.2ml或32μg/0.2ml,i.m.)预处理可分别取消组胺和PEA的抑胃酸效应。这些结果提示:脑内组胺可能参与胃酸分泌中枢调节。其抑制效应似通过H_1受体介导;双重效应的机制有待进一步研究。     

玉米赤霉烯酮在小鼠体内的致突变性研究

用小鼠骨髓细胞微核试验和染色体畸变试验评价了赤霉病麦毒素之一玉米赤霉烯酮的体内致突变效应。玉米赤霉烯酮的试验剂量为0,0.1,1.0,10.0,100.0mg/kg体重,以环磷酰胺为阳性对照。实验结果表明,玉米赤霉烯酮各试验剂量组的微核发生率和染色体畸变率与阴性对照组相比均无显著性统计学差异,亦未发现有明显的性别差异。     

玉米赤霉烯酮在小鼠体内的致突变性研究*

用小鼠骨髓细胞微核试验和染色体畸变试验评价了赤霉病麦毒素之一玉米赤霉烯酮的体内致突变效应。玉米赤霉烯酮的试验剂量为0,0.1,1.0,10.0,100.0mg/kg体重,以环磷酰胺为阳性对照。实验结果表明,玉米赤霉烯酮各试验剂量组的微核发生率和染色体畸变率与阴性对照组相比均无显著性统计学差异,亦未发现有明显的性别差异。     

PTSD样大鼠海马MR和GR变化的研究

目的研究PTSD大鼠海马神经元核受体MR(mineralocorticoid receptor,盐皮质激素受体)和GR(glu-cocorticoid receptor糖皮质激素受体)表达的变化。方法采用国际认定的SPS方法刺激大鼠建立PTSD大鼠模型,分别取SPS处理后24h、7d、14d大鼠脑组织;同时取正常脑组织(非SPS刺激)作为对照,应用免疫组化、Western Blot方法分别进行各组海马神经元GR和MR表达变化的观察及定量检测。结果(1)经SPS处理后,免疫组化和Western Blot结果显示海马神经元MR表达呈现随着24h、7d、14d逐渐下调的趋势;(2)经SPS处理后,免疫组化和Western Blot结果显示海马神经元GR表达于24h时下调,而7d、14d时呈现逐渐回升趋势。结论大鼠经SPS处理后,海马MR表现为持续下调状态;而GR表达为短暂下调,随后回调,揭示PTSD大鼠海马神经元核受体—MR和GR的表达变化可能是引发海马功能降低的重要因素之一。     

丹参对鼠缺血后残肝酶组织化学的影响

研究观察鼠缺血后肝再生时酶组织化学的变化。结果表明缺血后肝再生时肝细胞ＳＤＨ、Ｇ６Ｐａｓｅ和Ｍｇ２＋ＡＴＰａｓｅ活性及ＰＡＳ反应均在不同程度上低于对照组,而ＬＤＨ、ＡＣＰ活性较对照组有不同程度升高。丹参组酶活性及ＰＡＳ反应基本处于缺血组与对照之间,说明丹参对保护某些酶活性,促进肝再生有一定的作用     

H3受体在5-羟色胺诱导大鼠瘙痒初级传入通路中作用

目的观察H3受体激动剂（R-α-甲基组胺）和拮抗剂（噻普酰胺）对5-羟色胺（5-HT）诱导大鼠搔抓行为的影响,并探讨H3受体在大鼠瘙痒初级传入通路中的作用。方法29只SD大鼠随机分为4组,分别在颈背部皮内注射生理盐水（生理盐水组）、2%5-HT（5-HT组）、R-α-甲基组胺＋5-HT（甲基组胺组）、噻普酰胺＋5-HT（噻普酰胺组）,摄像并计数注射后1 h内搔抓次数。取大鼠C3-C5及其相应节段的背根神经节（DRG）作H3R免疫组化染色。结果5-HT组大鼠的搔抓次数明显多于生理盐水组（P〈0.01）,而R-α-甲基组胺或噻普酰胺预处理可分别减少或增加大鼠搔抓次数（P〈0.01）。5-HT组大鼠脊髓后角浅层中H3受体表达与生理盐水组相比差异无显著性（P〉0.05）,而R-α-甲基组胺或噻普酰胺预处理可分别减少或增加H3受体表达（P〈0.01-0.05）。各组动物DRG内,H3受体阳性中、小型神经细胞的比值差异无统计学意义（P〉0.05）。结论在5-HT诱导大鼠急性瘙痒模型中,脊髓背角胶状质区内H3受体激活可减弱瘙痒,但DRG内中、小型神经细胞上H3受体表达可能不参与瘙痒信号的传导。     

L-NNA对大鼠急性脊髓损伤的影响

实验采用雌性 Wistar大鼠 41只 ,分为正常对照组、生理盐水对照组和 L - NNA治疗组 ,后两组制成不完全性(2 18克厘米力 )急性脊髓 (第 10胸髓 )损伤模型 ,于术后每天一次腹腔注射 L - NNA (2 0 m g/ kg)或等量生理盐水 ,连续四周 ,然后处死动物 ,行脊髓 NOS染色和超微结构观察。结果显示 ,L - NNA治疗组脊髓 NOS阳性神经元染色较生理盐水对照组浅 ,两组光密度比较 P<0 .0 5 ;超微结构观察 ,生理盐水对照组脊髓神经元胞质呈空泡样变 ,线粒体等细胞器变性 ,髓鞘严重变形 ,少数髓鞘呈线团状改变 ,常伴有高电子密度的块状沉积物。但 L - NNA治疗组脊髓神经元及大部分神经纤维的髓鞘结构清晰。因此我们认为 ,大鼠急性脊髓损伤可诱导神经元 NOS表达 ,L - NNA对其损伤修复起促进作用。     

性激素对大白鼠胃粘液分泌的影响

通过雄、雌性大鼠去势,怀孕鼠,以及肌肉注射性激素的方法,观察内,外源性激素对胃粘液分泌的影响,采用Ａｌｃｉａｎ ｂｌｕｅ与胃液和胃壁粘液中糖蛋白结合的方法进行胃粘液测定,结果表明：雄、雌鼠胃粘液分泌无性别差异,去势夺雄、雌鼠胃粘液分泌无明显影响;怀孕鼠胃粘液分泌增加,丙酶睾酮对去势雄、雌鼠胃粘液分泌无影响,而戊酸雌二醇和孕酮可增加胃粘液分泌,提示：怀孕鼠胃粘液分泌的增加可能与雌激素和孕激素分泌增多     

饥饿对大鼠胰岛素分泌的影响及其机制的分析

本工作探讨了大鼠饥饿时胰岛素分泌减少的机制。大鼠连续饥饿1至4d,其血浆胰岛素水平的变化不与血糖平行,二者虽均于饥饿第1天即显著下降,但胰岛素在饥饿期间一直维持于低水平。而血糖则于饥饿第3天开始回升,第4天接近正常水平。在离体实验中发现,禁食3d大鼠的离体灌流胰腺对精氨酸的胰岛素分泌反应明显地低于正常摄食大鼠。看来,饥饿时胰岛素分泌的减少似不是由于营养物质对胰岛β细胞刺激作用的减弱,而可能是由于局部抑制性影响加强所致。 我们进一步观察了胰内生长抑素的作用,发现饥饿3d的大鼠,在胰岛素分泌减少的同时,胰腺生长抑素的含量增高,如预先给动物注射半胱胺以耗竭内源性生长抑素,则使饥饿大鼠胰岛素分泌的抑制现象明显减轻。在离体实验中也发现,预先注射半胱胺的饥饿大鼠,其离体灌流的胰腺对精氨酸的反应恢复正常。这些结果提示,胰内生长抑素对β细胞局部抑制作用的增强,可能是饥饿引起胰岛素分泌减少的机制之一。     

实验性高血压大鼠室旁核加压素分泌的免疫细胞化学研究

精氨酸加压素（AVP）主要是由下丘脑室旁核（PVN）和视上核（SON）的加压素能神经元合成分泌。近年来的研究表明,AVP作为一种血管活性肽与高血压的发病有关。本文采用二肾一夹法制成高血压模型。应用光、电镜技术、免疫细胞化不技术和图象分析技术对实验性高血压大鼠PVN加压素神经元进行了研究,并与SON加压素神经元及正常大鼠进行比较,研究结果表明,实验性高血压大鼠PVN和SON内AVP阳性细胞中分泌颗粒密集呈棕黄色,正常大鼠组染色浅谈。图象分析检测两组PVN和SON中AVP阳性细胞平均灰度值,所得数据分别经统计学处理,实验组和正常组AVP神经元在PVN有显著性差异。在SON也有显著性差异。但在实验组内的PVN和SON之间无显著性差异,正常大鼠组PVN和SON之间亦无显著性差异。结果表明, 高血压大鼠在血压升高时,PVN和SON内加压素神经元的分泌增强。     

电针对局灶性脑缺血大鼠脑内神经生长因子受体trkA的影响

神经生长因子对神经元凋亡有拮抗作用,其作用方式是通过特异性受体——ｔｒｋＡ实现。为了探讨针刺对内源性抗凋亡因素的调节作用。本研究用大鼠局灶性脑缺血再灌注模型,应用免疫组织化学方法观察缺血再灌注时ｔｒｋＡ的变化及针刺对ｔｒｋＡ的影响。结果发现：缺血组对照侧大脑皮层偶见散在ｔｒｋＡ免疫阳性神经元,缺血侧大脑皮层ｔｒｋＡ阳性神经元与对照侧相比,显微镜下见无显著性差异。电针组缺血侧大脑皮层见大量ｔｒｋＡ免疫反应阳性神经元,主要分布于半影区,与对照侧及未电针的缺血侧相比,显微镜下见阳性神经元数目有差异。结果提示：电针可以诱导脑缺血时神经营养因子受体表达,调动机体内抗凋亡因素的作用。     

大鼠脊髓损伤后表皮生长因子受体在脊髓的表达特点

目的研究大鼠脊髓损伤(spinal cord injury,SCI)后表皮生长因子受体(epidermal growth factor re-ceptor,EGFR)在脊髓的表达特点及意义。方法健康成年雄性SD大鼠,随机分为4组(每组10只):假手术组,SCI术后3 d、7 d和14 d组。应用Basso Beattie Bresnahan(BBB)评分观察大鼠行为学改变;逆转录-聚合酶链反应(RT-PCR)检测损伤段脊髓组织中EGFR mRNA表达水平;免疫组织化学方法观察损伤段脊髓灰质中EGFR蛋白表达情况;并对EGFRmRNA及蛋白表达情况与BBB评分进行相关性分析。结果行为学观察发现大鼠脊髓损伤后下肢神经功能逐步恢复;RT-PCR结果显示EGFR mRNA在假手术组大鼠脊髓中微量表达,SCI术后3 d表达显著升高,随后趋于下降,14 d时仍高于假手术组(P<0.01);免疫组织化学染色显示损伤段脊髓灰质中EGFR阳性细胞数在损伤后3 d显著高于假手术组(P<0.01),随后趋于下降,但14 d时仍高于假手术组(P<0.01);EGFR mRNA及蛋白的表达均与BBB评分呈显著负相关(r=-0.956,P<0.05;r=-0.966,P<0.05)。结论EGFR在大鼠脊髓损伤后具有时相分布特点,且与动物行为呈负相关,提示其表达可能阻碍损伤后的神经功能恢复。     

雌激素和孕激素对切除卵巢大鼠血清胃泌素水平和胃酸分泌的影响

卵巢切除两周后大鼠血清胃泌素水平升高和胃酸分泌增加;给予苯甲酸雌二醇(10μg/d)可完全阻止这两种变化,但补充黄体酮(0.2mg/d)对卵巢切除大鼠的血清胃泌素水平无影响,仅明显减少胃酸分泌。本实验结果提示,雌激素对于雌性大鼠的胃泌素释放和胃酸分泌具有抑制作用,孕激素也有抑制胃酸分泌的作用,这些作用不是摄食量改变的结果.     

第三脑室注射组织胺增强五肽促胃液素诱导的胃酸分泌的作用机制

本文探讨中枢组织胺增强胃酸分泌的作用机制。雄性ＳＤ大鼠重２００－３００ｇ,用３７℃生理盐水做恒速,连续胃灌流。膈下迷走神经切除后,观察第三脑室或外周给药对五肽促胃激素诱导的胃酸分泌及对血交涉以质酮水平的影响。结果如下：１．第三脑室注射１．０μｇ组织胺增强Ｇ－５诱导的胃酸分泌,这作用可为预先肌肉注射苯海拉明８．０μｇ听阻断。２．脑注射促肾上腺皮质激素释放因子增强因酸分泌,且呈量效关系。３．脑室注射组     

EFFECTS OF UTERINE DISTENSION AND OESTRADIOL ON CELL KINETICS IN THE ENDOMETRIAL EPITHELIUM OF OVARIECTOMIZED RATS

Cell kinetics in the uterine epithelium of ovariectomized rats were studied after uterine distension and/or an oestradiol injection, by cumulative ³H-TdR labelling and percentage of labelled mitoses (PLM). With both methods it was found that distension shortens the total cell cycle at the expense of G₁ more than does oestradiol. Both treatments act in a cumulative manner since the greatest reduction in T_c is observed after distension plus oestradiol. PLM curves showed that distension and/or oestradiol induce a 30% reduction in S phase duration. The evolution of percentages of labelled cells and colchicine-blocked mitoses after these treatments confirms their additive effects and indicates that the mitogenic action of oestradiol is delayed compared to that of distension. It is suggested that these factors stimulate epithelial cell division in the uterus through partly different metabolic channels.     

缩胆囊素、胃泌素及丙谷胺对大鼠胆汁分泌的影响

本文旨在研究五肽胃泌素(P-Gas)、缩胆囊素(CCK)与其受体拮抗剂丙谷胺(PGM)单独静脉输注或联合应用对大鼠胆汁流量及胆汁成分排泌量的影响。结果表明:(1)P-Gas无利胆作用;(2)CCK-8仅少量增加胆汁及 HCO_3~-的分泌量;(3)PGM 明显地增加胆汁及胆汁中 HCO_3~-和 CI~-的排泌量,但胆酸分泌量不增加;(4)当 CCK-8 2.3μg/(kg·h)静脉灌注与 PGM 200mg 灌胃联合应用时,胆汁、HCO_3~-和 CI~-的排泌量进一步增加,但P-Gas 2μg/(kg·h)与 PGM 联合应用时的胆汁排泌量低于单独应用 PGM 组。以上结果证明:PGM 有明显的促胆汁分泌作用,其机制属于非胆酸依赖性利胆、而CCK-8只是胆汁分泌的微弱刺激剂,P-Gas 则无利胆作用。在 CCK-8与 PGM 二组间,似有促胆汁分泌的协同作用;但表现在 P-Gas 与 PGM 二组间的作用,似为一种拮抗作用。     

酪氨酸对大鼠子宫胞浆雌,孕激素受体的影响

采用放射受体分析法,测定了动情周期不同阶段及去卵巢大鼠子宫胞浆雌二醇和孕酮受体含量,并观察了子宫腔内注射酪、丝、苏三种氨基酸对子宫胞浆雌。醇、孕酮受体含量的影响。结果表明：（１）Ｌ－酪氨酸对动情前期、动情期、间情期大鼠子宫胞浆雌二醇和孕酮受体都具有明显的降低作用。（２）Ｌ－酪氨酸也降低去卵巢大鼠子宫胞浆雌二醇和孕酮含量,即这一作用不是通过影响卵巢激素分泌实现的。（３）Ｌ－苏氨酸仅可降低动情期和间情期大鼠子宫胞浆孕酮受体含量,而对相应周期雌二醇受体没有明显作用。（４）Ｌ－丝氨酸和Ｌ－苏氨酸对去卵巢大鼠子宫胞浆雌二醇和孕酮受体均无影响。