异丙肾上腺素对心内神经节中肽能递质VIP影响

异丙肾上腺素是临床常用的心脏骤停的抢救药物。为了研究该药对心内神经节中肽能递质的影响,本文在大鼠皮下注射异丙肾上腺素５ｍｇ／ｋｇ,连续三天,后固定取心房后壁,用免疫组化结合图像分析,观察心内神经节中肽能递质ＶＩＰ的变化。对照组大鼠心内神经节中含有ＶＩＰ免疫反应（ＶＩＰ－ＩＲ）阳性神经纤维和胞体;实验组大鼠心内神经节中含有ＶＩＰ－ＩＲ阳性神经纤维和胞体呈不同程度增多。其中ＶＩＰ－ＩＲ阳性神经纤维积分光密度较对照组增加２５．３％,而神经胞体积分光密度只增加８．１％。结果提示：１．大鼠心内神经节中ＶＩＰ－ＩＲ阳性神经纤维可能有两个来源：即心内ＶＩＰ－ＩＲ阳性神经节细胞和心外副交感神经元;２．异丙肾上腺素对心脏的作用并非单一的直接作用,其中部分是通过影响心内神经节中肽能递质的变化而发挥间接作用。     

肾上腺素能神经纤维的化学介质——去甲肾上腺素

神经冲动的化学传递是生理学中一个重要问题。在植物性神经系统中,胆碱能纤维末梢通过释放乙酰胆碱而起作用,但交感神经节后肾上腺素能纤维末梢释放的化学介质究竟是什么,直至近十余年才逐渐阐明。根据研究资料,可以肯定肾上腺素能神经纤维的化学介质主要是去甲肾上腺素(noradrenaline)。去甲肾上腺素的化学构造式为     

异丙肾上腺素对大鼠心内神经节中生长抑素(SS)影响的研究

研究异丙肾上腺对心内神经节中肽能神经递质 SS的影响 ,本文在大鼠皮下注射异丙肾上腺素 5 m g/ kg,连续三天 ,固定后取心房后壁 ,用免疫组织化学结合图像分析方法观察大鼠心内神经节中肽能递质 SS的变化。对照组大鼠心内神经节中含有 SS免疫反应 (SS- IR)阳性神经纤维和细胞 ;实验组大鼠心内神经节中 SS- IR阳性神经纤维和神经元的积分光密度均明显减低。结果说明异丙肾上腺素可降低心内神经节中 SS含量 ,提示 ,异丙肾上腺素的正性变时和变力作用可能通过降低 SS的含量来实现。     

异丙肾上腺素对大鼠心骨神经节中生长抑素（SS）影响的研究

研究异丙肾上腺对心内神经节中肽能神经递质SS的影响。本在大鼠皮下注射异丙肾上腺素5mg/kg,连续三天,固定后取心房后壁,用免疫组织化学结合图像分析方法观察大鼠心骨神经节中肽能递质SS的变化,对照组大鼠心内神经节中含有SS免疫反应（SS－IR）性神经纤维和细胞,实验组大鼠心内神经节中SS－IR阳性神经纤维和神经元的积分光密度均明显减低。结果说明异丙肾上腺素可降低心内神经节中SS含量,提示,异丙肾上腺素的正性变时和变力作用可能通过降低SS的含量来实现。     

嘌呤能神经假说

1898年,Langley 注意到,刺激迷走神经可引起胃舒张,用阿托品阻断胆碱能神经后,表现更明显。此后,又有报道,胃肠道和膀胱也有类似现象。最初认为,这是走行于迷走神经中的肾上腺素能神经纤维的作用;但后来用溴苄胺和胍乙啶阻断肾上腺素能神经,这种舒张反应仍存在,因此,用肾上腺素能神经已不能解释此现象。1962年,Burnstock 等在用     

豚鼠胆囊SP免疫组织化学反应特点及电镜观察

研究采用ABC免疫组化方法及电镜观察发现;豚鼠胆囊含有SP免疫反应的神经元,神经纤维及肥大细胞,这些神经纤维束是被神经膜细胞完全或不完全包裹的无髓神经纤维。其神经纤维内含有的突触小泡形态大小不一。电镜下分可为3种类型;（1）以小型无芯小泡为主以及少量大型有芯小泡。（2）以小型有芯小泡为主以及少量无芯小泡和大型有芯小泡。（3）以大型有芯小泡为主以及少量小型无芯小泡。用SP免疫电镜组化方法观察。豚鼠胆囊的SP免疫反应阳性神经纤维内散在分布的突触小泡多为第3种。但在血管,淋巴管周围SP免疫反应阳性神经纤维内的突触小泡多为小型有芯小泡,胆囊除了受肾上腺素能神经支配外,尚受SP等肽能神经的支配。本研究对豚鼠胆囊SP免疫组织化学反应阳性神经纤维分布特点及神经纤维内突触小泡的超微结构特点进行了研究。     

细胞外基质对神经纤维生长的作用

近几年研究细胞外基质促进神经纤维生长的作用有惊人的发展。施旺细胞、未分化的神经胶质细胞,以及胚胎非神经细胞和神经细胞所形成细胞外基质中,层粘连蛋白分子(或它的亚单位、或它与其他分子结合的复合物等不溶性物质)与生长锥相互作用的结果对刺激和诱导神经纤维的生长起重要的作用。其他分子或可溶性物质对纤维生长也有一定的作用。以基膜形式存在的细胞外基质是促神经纤维生长最好的基底,并为脑损伤修复提供了应用前景。     

肾上腺素受体对心血管细胞生长和凋亡的影响

肾上腺素受体广泛存在于心血管系统。心肌肥厚,心衰,心动粥样硬化等病理过程往往伴有心血管细胞的异常生长和凋亡,研究表明儿茶酚胺可经不同的肾上腺素受体通过不同的信号转导途径,如α－肾上腺素受体主要通过磷酯磷Ｃ／蛋白激酶Ｃ途径,β－肾上腺素受体则主要通过蛋白激酶Ａ／ｃＡＭＰ途径或激活钙通道对心肌细胞,血管平滑肌细胞,内皮细胞等的生长与凋亡产生影响,探讨肾上腺素受体对心血管细胞生长和凋亡的作用机制,具有重     

大鼠脑内血管的单胺能神经分布——免疫组织化学法研究

本实验应用ABC免疫过氧化物酶法,以酪氨酸羟化酶(TH)作为标记物,观察了10只Wistar大鼠脑实质内血管的中枢去甲肾上腺素能神经分布。脑实质内血管壁明显可见免疫反应阳性去甲肾上腺素能神经纤维。对端脑皮质、海马、下丘脑、脑桥、延髓各部位血管的神经形态进行了描述。皮质血管的阳性纤维数量较多,纤维较细,相互交织成网,膨体可见;髓质内血管的阳性纤维较稀,似线样结构。讨论了中枢去甲肾上腺素能神经对脑实质内血管以及局部脑循环的作用。     

不同基底对培养鸡胚视网膜神经纤维生长作用的计算机辅助定量研究~*

以天然的细胞外基质——鸡胚视网膜基膜作为培养基底,用层粘连蛋白、纤维粘连蛋白、多聚赖氨酸和鼠尾胶等物质包被的表面为人工培养基底,比较了孵育10天的鸡胚视网膜条在这些不同培养基底上神经纤维生长的图像。第一次尝试用计算机对多根神经纤维的生长图像进行辅助定量分析。选择的四个参数是每根神经纤维平均总长度(L)、平均偏转角度(Q)、平均弯曲度(R)和平均分支点数(B)。结果表明,纤维生长图像的各个参数值和培养基底密切相关。     

小鼠颌下腺内交感神经末梢变性时程的性差异

外源性神经生长因子(NGF)对周边交感系统的营养性影响已有广泛的研究(Black,1978;Purves等,1978)。但是,内源性NGF是否同样行使这种影响,至今还没有被人证实(Nja等,1978)。1979年,Carstairs等人利用丙酸睾酮慢性处理,提高小鼠颌下腺内NGF含量以后,观察到颈上神经节(SCG)中有部分神经元肥大,但其它交感神经节不受影响。作者认为SCG内肥大的神经元就是支配颌下腺的那部分交感神经元。由于雄性小鼠颌下腺内的NGF含量是雌性小鼠的92倍(Hirata等,1979),我们实验室直接检查了小鼠颌下腺和虹膜的交感神经支配,发现成年雄性小鼠颌下腺的荧光基丛索远较雌性小鼠的     

在给利血平后的恢复中小鼠颌下腺的去甲肾上腺素含量与神经生长因子水平的关系

给ICR/JCL品系的成年小鼠1次注射利血平(2mg/kg体重)后24小时,其颌下腺(SMG)的去甲肾上腺素(NA)贮存能够被耗竭。在注射后第12天,NA 含量恢复到利血平处理以前的水平。在恢复过程中,雄性腺体的 NA 含量均为雌性的2倍左右。切断颈上神经节(SCG)的节前神经,雌雄腺体的 NA 含量都下降至对照侧的80%左右。消除节前神经的影响以后,在 NA 的恢复过程中,雄性腺体的 NA 含量仍然是雌性的2倍左右。利用神经生长因子(NGF)生物测定法,我们测得本品系成年雄性小鼠 SMG 的 NGF 含量为雌性小鼠的94倍左右。正如外源性 NGF 能选择性地提高交感神经元内的酪氨酸羟化酶活力与 SMG 的 NA 含量一样,在利血平处理后的恢复过程中,雄性腺体比雌性腺体具有较高的 NA 含量可能是由于内源性 NGF 对交感神经元内酪氨酸羟化酶产生效应的结果。     

Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 microgram of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay, SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P less than 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P less than 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 micrograms/d) of adult mice, SMG weight in NH mice increased significantly (P less than 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mouse epidermal growth factor concentrations are altered by gonadectomy and treatments with estradiol and progesterone

In adult male and female mice we compared the epidermal growth factor (EGF) concentrations after gonadectomy and studied the effects of postgonadectomy treatments with estradiol and progesterone. In gonadectomized mice the mean concentration of EGF in the submandibular salivary gland (SMG) was (7-fold) higher in the females than the males. In the kidneys the males had (1.3-fold) higher levels of EGF than the females. Yet, gonadectomized males had higher plasma EGF levels and females higher urinary EGF concentrations. Estradiol treatment clearly decreased the EGF concentration in the SMG and increased it in urine and kidneys. Progesterone decreased male kidney EGF. Combined treatment with estradiol and progesterone increased the EGF concentration in the male urine and SMG, and decreased it in male kidneys.     

海马内移植颈上神经节组织改善穹窿－海马伞横切大鼠的记忆功能

３８只Ｗｉｓｔａｒ大鼠双侧穹窿－海马伞损伤后．以被动回避反应为指标观察到记忆明显受损,与损伤前相比,有记忆动物自６５．３％降至１３．６％,两者差别非常显著。于穹窿－海马伞损伤后记忆丧失动物（ｎ＝１５）自体一侧分离出颈上神经节（ＳＣＧ）,切为２－３块并在室温下孵育于２０—５０μｇ／ｍｌ２．５ｓＮＧＦ中１—２ｈ,而后移植于自体双侧海马背侧,移植４周后观察到动物记忆明显恢复,恢复记忆的动物数占７３．３％。在行为实验基础上应用荧光组化方法检查了移植细胞成活情况并测量了海马内去甲肾上腺素（ＮＡ）的含量。移植后２周海马内ＮＡ含量比损伤组有明显上升。移植后一个月,可见部分移植细胞成活并有神经纤维生长。实验表明．穹窿－海马伞损伤大鼠海马内自体移植ＳＣＧ,通过神经递质的局部补充对动物丧失的记忆能力具有一定改善作用。     

Tissue-specific regulation of the expression of rat kallikrein gene family members by thyroid hormone.

We have altered the thyroid hormonal status of both male and female rats and examined the expression of six functional members of the rat kallikrein gene family (PS, S1, S2, S3, K1 and P1) in the submandibular gland (SMG), kidney, prostate, testis and anterior pituitary gland (AP) of these animals. On Northern-blot analysis with gene-specific oligonucleotide probes, the steady-state mRNA levels of S1, S2, S3, K1 and P1 were all dramatically altered in the SMG of male and female rats treated with propylthiouracil (PTU; 100 mg/litre of drinking water) or thyroxine (T4; 10 micrograms/100 mg body wt.) for 3 weeks. The SMG mRNA levels of these five genes were all lowered (30-90%) in hypothyroid (PTU-treated) male and female rats and elevated (1.4-4-fold, male; 1.5-11-fold, female) in the hyperthyroid (T4-treated) and PTU/T4-treated animals. In contrast, PS (true kallikrein) mRNA levels in the male or female SMG or kidney were essentially unchanged. K1 mRNA levels in the kidney were considerably less responsive to thyroid status than those in the SMG. Changes in S3 and P1 mRNA levels in the prostate were also variable, but essentially unaffected by these treatments. AP PS mRNA levels were also unaffected by changes in thyroid-hormonal status, as were levels of a novel P1-like mRNA in the testis. In summary, these studies demonstrate that the same kallikrein gene family member(s) may be differentially regulated by thyroid hormones in the rat SMG, kidney, prostate and pituitary, and thus further extend the concept of tissue-specific expression and hormonal regulation of the kallikrein gene family in the rat.     

Molecular mechanism of tissue-specific regulation of mouse renin gene expression by cAMP. Identification of an inhibitory protein that binds nuclear transcriptional factor.

Renin gene expression in the mouse kidney and submandibular gland (SMG) are differentially regulated by cAMP. In this study, we examined the potential molecular mechanism responsible for this tissue-specific regulation. 32P end-labeled synthetic oligonucleotide containing mouse renin cAMP-responsive element (CRE) was incubated with kidney nuclear extracts from either control or cAMP-treated mice and analyzed by gel mobility shift assay. Our results demonstrated that cAMP induced a nuclear protein which complexed with the CRE oligonucleotide in a specific manner. This nuclear protein-DNA binding was competed effectively by the oligonucleotide containing human chorionic gonadotropin alpha-subunit CRE but not by the mouse renin DNA fragment from which the CRE was deleted by site-directed mutagenesis. In contrast, no DNA-protein complex formation could be detected when this [32P]CRE oligonucleotide was incubated with the SMG nuclear extract from control or cAMP-treated mice. However, CRE-binding protein complex formation was demonstrated in the SMG nuclear extract when the incubation was performed in the presence of 0.8% sodium deoxycholate and 1.2% Nonidet P-40, detergents that dissociate protein-protein complexes. Furthermore, in the absence of deoxycholate, we observed that SMG nuclear extract attenuated the binding of the kidney CRE-binding protein to mouse renin CRE in a dose-dependent manner and this inhibitory effect of SMG nuclear extract disappeared in the presence of sodium deoxycholate. This inhibitory nuclear protein in SMG is specific for CRE-binding protein since it does not affect nuclear protein binding to synthetic DNA oligonucleotides of human collagenase AP-1 and human metallothionein AP-2. Our data further suggest that inhibitory nuclear protein is present in lower quantities in other extrarenal tissues, i.e. testes, liver, brain, heart, but is not detectable in the kidney. Taken together, these results suggest that the SMG and certain extrarenal tissues contain nuclear trans-acting factor(s) that interact with CRE-binding protein, thereby interfering with its binding to mouse renin CRE. The presence of this inhibitory protein in the mouse SMG nucleus may contribute to the tissue-specific regulation of the renin gene expression by cAMP.     

Histopathologic findings and establishment of novel tumor lines from spontaneous tumors in FVB/N mice

The inbred FVB mouse strain is used extensively in cancer research. Transgenic mice with an FVB/N background in which the expression of green fluorescent protein is under the control of various promoters have been used widely for the last decade. However, little is known about the incidence and characteristics of spontaneous tumors in these mice. In addition, only a few tumor lines have been established for use in this particular mouse strain. Our aim was to initiate a database of spontaneous tumors in our retired FVB/N breeders, analyze the histopathologic characteristics of these tumors, and establish novel tumor lines in vivo and in vitro. A total of 234 (40 male, 194 female) breeder mice were observed during their natural lifespans. The incidence of spontaneous tumors was 45.0% in male mice and 52.8% in female mice. All tumors in male mice were lung alveolar-bronchiolar (AB) neoplasms, except for 1 testis interstitial cell tumor. In female mice, histopathologic examination revealed 48 lung AB tumors, 27 mammary gland tumors, 13 ovarian tumors, and 14 other tumors. Several of these spontaneous tumors have been transplanted into FVB/N mice. One mammary adenocarcinoma (MCaP0008) and 1 lung AB carcinoma (LAP0297) were successfully transplanted subcutaneously and passaged serially in vivo. Subsequently, we established cell lines from both tumors, which were maintained in monolayer in vitro. Both of the grafted tumors and cell lines are tumorigenic in VEGF(P)-GFP/FVB and Tie2(P)-GFP/FVB mice. Establishment of these novel tumor lines will benefit both in vivo and in vitro studies on the pathophysiology of cancer in this relatively new but widely used mouse strain.     

Regulation of nerve growth factor synthesis in mouse submaxillary glands by testosterone.

—It has long been known that the activity of nerve growth factor (NGF) in extracts obtained from the male mouse submaxillary gland is higher than in extracts from the female gland, and that the activity present in female glands can be increased by testosterone treatment. This communication presents a study of the mechanism of the testosterone effect. Of several different steroids administered to female Swiss–Webster mice only testosterone propionate led to increased gland NGF activity. The increase did not appear to be due to an enhancement of the activity of pre-existing molecules on sympathetic nerve fiber outgrowth, or due to an altered affinity for the specific antibodies used in the estimation of NGF content, but appeared rather to be due to an accumulation of NFG molecules. The kinetics of change in the male gland NGF content upon castration and secondary testosterone propionate stimulation was analyzed by application of the plateau principle. The rate of loss of NGF from this organ was not measureably different between the castrate and testosterone propionate stimulated state. On the other hand, there was estimated to be a 10-fold difference in the rate of input between the basal and steroid stimulated state. Tracer amounts of radioiodine labelled NGF administered i.v. was not accumulated by the gland, and there is no evidence for uptake of this protein from the circulation. We, therefore, infer that the increased NGF concentration in male submaxillary glands is due to a 10-fold increase in the rate constant of synthesis.