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1.
3-nitropropionic acid (3-NPA) is a toxin sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neurological disorders when consumed by humans. In vitro, 3-NPA irreversibly inactivates SDH, a Complex II respiratory enzyme required for mitochondrial energy production. A single dose of 3-NPA (30 mg/kg S.C.) was given to singly-caged adult male Sprague-Dawley rats. Rectal temperature was measured after dosing as a potential biomarker of exposure to 3-NPA, and animals were sacrificed at various times after 3-NPA exposure for histochemical visualization of SDH activity. 3-NPA-treated rats experienced a progressive hypothermia, which reached a loss of 3°C or more in core body temperature by 3 hours after dosing. The optical density of the SDH stain in brain was reduced according to a similar time-course, most prominently in the cerebellum and least sharply in the thalamus. The caudate nucleus had the greatest density of SDH staining that we measured in brain; it also has been reported to be the region most consistently lesioned by 3-NPA. However, within other areas of brain such as subdivisions of the hippocampus, neither endogenous SDH activity nor its sensitivity to inhibition by 3-NPA could predict the susceptibility to neurodegenerative changes. Although SDH activity remained significantly reduced in most areas of brain (except thalamus) for up to 5 days after dosing, core temperatures had returned to control values by 5 days suggesting that animals can utilize an alternate method of heat production to withstand insult by 3-NPA. 相似文献
2.
C W Burger T Korsen H van Kessel P A van Dop F J Caron J Schoemaker 《The Journal of clinical endocrinology and metabolism》1985,61(6):1126-1132
To characterize the oscillations of plasma LH in normally cycling and amenorrheic women, three groups of women were studied: I, normal women during the follicular phase of the cycle (n = 9); II, women with polycystic ovarian disease (PCOD; n = 11); and III, women with non-PCOD secondary amenorrhea (n = 12). Blood samples were obtained at 10-min intervals for 6 h on 2 separate days. A pulse was defined as an increase in LH at least 20% over the preceding lowest value (nadir). Since LHRH release immediately follows the nadir of the LH levels, the nadir interval (NI) was used for analysis. For analysis, the results from 1 day were selected at random from each subject, and from each day, the same number of NIs also were randomly selected. When two NIs from each patient were selected, the median NI was 75 min in group I, 45 min in group II, and 45 min in group III. When three or four NIs were chosen, the median NI was 60 min in group I, 50 min in group II, and 40 min in group III. The differences between the groups were statistically significant. When three NIs were selected, the mean of the corresponding LH amplitudes was 2.8 U/liter in group I, 6.0 U/liter in group II, and 1.5 U/liter in group III. The differences between these groups were statistically significant. Thus, the NI in PCOD patients was shorter than that during the follicular phase of the cycle, but this short NI is not unique for PCOD, since the NI in non-PCOD secondary amenorrhea patients was even smaller. The LH amplitude was higher in PCOD and lower in non-PCOD secondary amenorrhea compared to that during the follicular phase of the cycle. The decrease in NI in PCOD and/or non-PCOD secondary amenorrhea vs. the NI of the follicular phase could be explained by either a higher frequency of LHRH pulses from the hypothalamus or an increased sensitivity of the pituitary leading to a greater response of the pituitary to LHRH pulses. 相似文献
3.
AIM We have discovered that Limonene modulates interdigestive myoelectrical complexes (IMCs) ofgastrointestinal tract in rats. In this research we will elucidate weather limonene affects acetylcholine M-receptor in caudate nucleus.METHODS Changes of IMCs were studied after limonene and/or atropine were microinjected into caudatenucleus. IMCs were recorded by a RM-6200 four-channel recorder and then delivered to Maclab and PowerMacintosh.RESULTS The active phases of IMCs occupied about 40% of total cycle in average. After microinjection oflimonene into caudate nucleus, the active phases were significantly shortened, while the cycle time of IMCswere not changed significantly. The inhibitory effects of limonene were abolished by pretreatment withatropine, whilst the atropine has no effect on IMCs.CONCLUSION It is suggested that limonene inhabits the gastrointestinal IMCs by affecting M-receptor incaudate nucleus. 相似文献
4.
BACKGROUND: In this study, we tested the hypothesis that long-term Rho-kinase inhibition would reverse nitro-L-arginine methyl ester-exacerbated nephrosclerosis in spontaneously hypertensive rats and attempted to elucidate the mechanism involved. METHODS: Five groups (each n = 8) were studied: untreated spontaneously hypertensive rats; nitro-L-arginine methyl ester (50 mg/l in drinking water, for 3 weeks)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester with fasudil (10 mg/kg/day)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester for 3 weeks followed by fasudil for 3 weeks-treated spontaneously hypertensive rats (same doses), and nitro-L-arginine methyl ester for 3 weeks followed by untreated for 3 weeks. We examined renal function, blood pressure, histological features, oxidative stress markers, and mRNA expression in the renal cortex. RESULTS: Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats had higher blood pressure, proteinuria, and serum creatinine and lower creatinine clearance, urinary NO3/NO2 ratio, and urinary cGMP excretion compared with control spontaneously hypertensive rats (all Ps < 0.05). Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats also had increased free radical metabolites and abnormal morphological findings with increased nicotinamide adenine dinucleotide phosphate oxidase activity, phosphorylation of myosin phosphatase targeting subunit-1, and mRNA expression of RhoA, RhoB, RhoC, collagen I and III, transforming growth factor-beta, nicotinamide adenine dinucleotide phosphate subunit, endothelial nitric oxide synthase, plasminogen activator inhibitor, and intercellular adhesion molecule-1 in the renal cortex compared with control spontaneously hypertensive rats. Long-term co-treatment with fasudil slightly improved these indices, but most of them were not statistically significant. Late fasudil treatment significantly improved kidney function, morphological changes, and alterations of mRNA expression in the renal cortex, although late untreated controls did not show any improvement. CONCLUSION: These results suggest that Rho-kinase inhibition partly reverses hypertensive glomerulosclerosis. The renoprotective effect of the Rho-kinase inhibitor may have multiple mechanisms including inhibition of extracellular matrix production, oxidative stress, adhesion molecule production, and antifibrinolysis. 相似文献
5.
OBJECTIVE: To identify the preservation of peritubular capillaries conferred by ramipril or valsartan treatment as an additional mechanism for their renoprotection. METHODS: The effect of ramipril or valsartan on peritubular capillaries was investigated in a remnant kidney model using male Sprague-Dawley rats sacrificed post-operatively at 3, 6 and 12 weeks respectively. Peritubular capillaries and tubulointerstitial hypoxia in untreated remnant kidney rats (n = 26), remnant kidney rats treated with ramipril (n = 22, 0.5 mg/kg/day), valsartan (n = 22, 30 mg/kg/day) or amlodipine (n = 22, 30 mg/kg/day) and sham-operated rats (n = 22) were assessed by CD141 and HIF-1alpha staining. RESULTS: Ramipril or valsartan significantly preserved the peritubular capillaries as well as renal function (p < 0.01). Tubulointerstitial hypoxia and tubular TGF-beta expression were noted well before the development of tubulointerstitial damage. The gentler slope of the relationship between HIF-1alpha scores and peritubular capillary density in individual rats was noted in both ramipril-treated and valsartan-treated groups compared to the untreated remnant kidney group (p < 0.05). CONCLUSIONS: Amelioration of peritubular capillary loss and subsequent tubular hypoxia by ramipril or valsartan treatment should be interpreted as an alternative type of their renoprotection, one which also implies a novel focus for clinical intervention. 相似文献
6.
目的探讨采用经额部入路2次注射自体动脉血的立体定向手术方法,改进大鼠尾状核脑出血模型的可行性。方法 SD大鼠16只,分为经额部入路组(8只)和经顶部入路组(8只)。2组分别在立体定向仪辅助下,自大鼠额部以及顶部入路进针至左侧尾状核中心,取股动脉血50μl分2次注入尾状核,观察比较2种不同方法所致血肿的形态及容量,并进行统计分析。结果所有大鼠左侧尾状核内均可见血肿形成。经额部入路组大鼠平均血肿容量(25.1±0.4)μl,明显多于经顶部入路组(24.2±1.0)μl,差异有统计学意义(P0.05)。2组血肿容量离散度分别为1.4%和4.2%。经额部入路组大鼠血肿形态较规则,优于经预部入路组。结论经额部入路2次注射自体动脉血技术是构建稳定大鼠尾状核脑出血模型的有效手段。 相似文献
7.
Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: characterization and localization of receptor binding sites in rat and human brain. 总被引:6,自引:2,他引:4
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J A Javitch G R Uhl S H Snyder 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(14):4591-4595
N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. [3H]MPTP binds with high affinity (Kd = 28 X 10(-9) M) to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity. Autoradiographic studies in human brain show very high receptor densities in the caudate, substantia nigra, and locus coeruleus, which may explain the neurotoxic and neurochemical sequelae of MPTP administration. In contrast to the human, rat substantia nigra and caudate display only moderate receptor concentrations. This species difference may explain the difficulty in producing selective nigrostriatal degeneration in rats. Sites densely labeled in rat brain include the locus coeruleus, interpeduncular nucleus, arcuate and periventricular hypothalamic nuclei, and the subfornical organ. 相似文献
8.
Fernandez-Ruiz J Wang J Aigner TG Mishkin M 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(7):4196-4201
Visual habit formation in monkeys, assessed by concurrent visual discrimination learning with 24-h intertrial intervals (ITI), was found earlier to be impaired by removal of the inferior temporal visual area (TE) but not by removal of either the medial temporal lobe or inferior prefrontal convexity, two of TE's major projection targets. To assess the role in this form of learning of another pair of structures to which TE projects, namely the rostral portion of the tail of the caudate nucleus and the overlying ventrocaudal putamen, we injected a neurotoxin into this neostriatal region of several monkeys and tested them on the 24-h ITI task as well as on a test of visual recognition memory. Compared with unoperated monkeys, the experimental animals were unaffected on the recognition test but showed an impairment on the 24-h ITI task that was highly correlated with the extent of their neostriatal damage. The findings suggest that TE and its projection areas in the ventrocaudal neostriatum form part of a circuit that selectively mediates visual habit formation. 相似文献
9.
The present study investigated the anatomical distribution of progestin target cells throughout the forebrain and midbrain regions of the 8-day postnatal female mouse. Female ICR mice were sc injected with 100 micrograms/100 g BW estradiol valerate on postnatal day 5 (birth = day 0). On postnatal day 8, treated mice were sc injected with 0.32 micrograms/100 g BW (Z)-17 beta-hydroxy-17 alpha-(2-[125I]iodovinyl)4-estren-3-one ([125I] progestin). For competition, additional estrogen-treated mice were each injected with 320 micrograms R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione; a potent synthetic progestin), 320 micrograms dihydrotestosterone, or 32, 160, or 320 micrograms corticosterone 1 h before [125I]progestin to show the specificity of [125I]progestin for the progestin receptor. Two hours after injection of [125I]progestin, the brains were removed, frozen, and processed for high resolution thaw-mount autoradiography. After 8-60 days of exposure, nuclear uptake and retention of [125I]progestin were detected in many brain regions, including the septum; bed nucleus of the stria terminalis; and preoptic area, periventricular nucleus, ventromedial nucleus, arcuate nucleus, and dorsomedial nucleus of the hypothalamus. In addition, labeling was seen in the cerebral cortex, caudate putamen, hippocampus, amygdala, and substantia nigra. Competition studies showed that excess R5020 prevented nuclear concentration of ligand, while dihydrotestosterone and corticosterone did not. The results indicate that the distribution of progestin target cells in extrahypothalamic regions of the developing brain is more extensive than that in the adult, while a similar topography was seen in the preoptic area and hypothalamus. The results further suggest that progestin action during brain development may influence the growth and development of target cells not only in the hypothalamus but also in regions of the brain previously not considered to be sites of hormone action. 相似文献
10.
Pilz B Shagdarsuren E Wellner M Fiebeler A Dechend R Gratze P Meiners S Feldman DL Webb RL Garrelds IM Jan Danser AH Luft FC Müller DN 《Hypertension》2005,46(3):569-576
We tested the hypothesis that the renin inhibitor aliskiren ameliorates organ damage in rats transgenic for human renin and angiotensinogen genes (double transgenic rat [dTGR]). Six-week-old dTGR were matched by albuminuria (2 mg per day) and divided into 5 groups. Untreated dTGR were compared with aliskiren (3 and 0.3 mg/kg per day)-treated and valsartan (Val; 10 and 1 mg/kg per day)-treated rats. Treatment was from week 6 through week 9. At week 6, all groups had elevated systolic blood pressure (BP). Untreated dTGR showed increased BP (202+/-4 mm Hg), serum creatinine, and albuminuria (34+/-5.7 mg per day) at week 7. At week 9, both doses of aliskiren lowered BP (115+/-6 and 139+/-5 mm Hg) and albuminuria (0.4+/-0.1 and 1.6+/-0.6 mg per day) and normalized serum creatinine. Although high-dose Val lowered BP (148+/-4 mm Hg) and albuminuria (2.1+/-0.7 mg per day), low-dose Val reduced BP (182+/-3 mm Hg) and albuminuria (24+/-3.8 mg per day) to a lesser extent. Mortality was 100% in untreated dTGR and 26% in Val (1 mg/kg per day) treated rats, whereas in all other groups, survival was 100%. dTGR treated with low-dose Val had cardiac hypertrophy (4.4+/-0.1 mg/g), increased left ventricular (LV) wall thickness, and diastolic dysfunction. LV atrial natriuretic peptide and beta-myosin heavy chain mRNA, albuminuria, fibrosis, and cell infiltration were also increased. In contrast, both aliskiren doses and the high-dose Val lowered BP to a similar extent and more effectively than low-dose Val. We conclude that in dTGR, equieffective antihypertensive doses of Val or aliskiren attenuated end-organ damage. Thus, renin inhibition compares favorably to angiotensin receptor blockade in reversing organ damage in dTGR. 相似文献
11.
V Paspaliaris S J Vargas M T Gillespie E D Williams J A Danks J M Moseley M E Story J N Pennefather D D Leaver T J Martin 《The Journal of endocrinology》1992,134(3):415-425
Classical pharmacological studies have shown that oestrogen dominance in humans and other animals can increase the responsiveness of the uterus to many locally acting peptides. Parathyroid hormone-related protein (PTHrP) has been shown to be expressed in the pregnant and non-pregnant rat uterus and exogenous PTHrP is known to relax uterine contraction in vitro. We investigated whether oestrogen dominance can influence the responsiveness of the uterine horn to PTHrP, and further studied the localization of PTHrP mRNA and protein in the rat uterine horn using in-situ hybridization and immunohistochemistry. Exogenous PTHrP(1-34) inhibited spontaneous and electrically induced contractions in uteri isolated from non-cycling rats. Pretreatment of non-cycling rats with oestradiol-17 beta increased uterine sensitivity to PTHrP: EC50 values for inhibition of spontaneous contractions by PTHrP were 0.33 nmol/l, 1.1 nmol/l, 2.6 nmol/l and 7800 nmol/l in uteri from animals treated for 2 days with oestradiol-17 beta alone, 2 days with oestradiol-17 beta + 1 day progesterone, 1 day with oestradiol-17 beta alone and in untreated rats respectively. Similar EC50 values were obtained for electrically stimulated uteri. In agreement with these findings, uterine horns from cycling rats in pro-oestrous and oestrous phases of the cycle showed a higher responsiveness to PTHrP(1-34) when compared with uterine horns taken from rats in metoestrus and dioestrus. PTHrP mRNA and protein were detected in the endometrial epithelium lining of the lumen and the endometrial glands, as well as in the myometrium of rats which were either pretreated for 2 days with oestradiol-17 beta or untreated. This study suggests that PTHrP may act in an autocrine and/or paracrine manner to modulate uterine motility and function. 相似文献
12.
Fetal Alcohol Exposure Alters the Induction of Immediate Early Gene mRNA in the Rat Prefrontal Cortex after an Alternation Task 总被引:2,自引:0,他引:2
Alan H. Nagahara Robert J. Handa 《Alcoholism, clinical and experimental research》1995,19(6):1389-1397
The present study examined fetal alcohol effects (FAE) on the induction of the immediate early genes (IEGs) c-fos, jun B, c-jun, and zif268 mRNAs in the prefrontal cortex, hippocampus, and other brain regions after testing in an alternation task. Subjects were female offspring of Sprague-Dawley rats fed either a 35% ethanol-derived calorie diet, pair-fed with sucrose, or control-fed with laboratory chow during the last week of gestation. At 75–85 days of age, rats were food-deprived and trained in a t-maze for food reward. Then rats were tested at 5-sec, 30-sec, or 60-sec delays on each of 6 days. On the day of killing, a subset of rats was tested at the 60-sec delay for 12 trials and killed 30 min after testing. The remaining animals were killed from their home cage and acted as controls. Expression of the four IEG mRNAs was examined in the brains of these animals using in situ hybridization. FAE rats showed a memory deficit at the 60-sec delay ( p < 0.05), but not at the 0-sec or 30-sec delays. Testing in the alternation task induced a significant elevation of c-fos, c-jun, jun B, and zif268 mRNA expression in the prefrontal cortex, hippocampal subfields CA1 and CA3, and several cortical areas. However, FAE rats showed a significantly smaller elevation of both c-fos and jun B mRNA levels in the orbital, prelimbic, and anterior cingulate regions of the prefrontal cortex ( p < 0.05). FAE animals also showed a lower expression of jun B mRNA in the caudate nucleus. Significant correlations between the mean performance at the 60-sec delay and mRNA expression of c-fos, jun B, and zif268 in the prefrontal cortical regions ( p < 0.05) were observed. These findings suggest that fetal alcohol exposure produces changes in the adult prefrontal cortex that may contribute to the behavioral deficit in the alternation task. 相似文献
13.
Treatment of normal rats with diphenylhydantoin (DPH) decreases serum thyroxine (T4) and triiodothyronine (T3) levels without the anticipated rise in serum thyrotropin (TSH). The present work has studied the intrapituitary conversion of T4 to T3 in male Wistar rats, 200-250 g body weight (BW), treated with DPH 5 mg/100 g BW/day for 8 days. A tracer dose of 3',5'-[125I]T4 (150 microCi) was injected intravenously, and 2 h later hypophyses were removed and homogenized individually at 4 degrees C in ice-cold PBS buffer (pH 7.4). T4 and T3 were extracted in 400 microliters n-butanol:2 N HCl (9:1) and chromatographed in tertiary amyl alcohol:hexane: 1 N ammonia (5:1:6). In 11 untreated control rats, [125I]T3 generated from [125I]T4 deiodination was 35 +/- 6% and intact [125I]T4 was 49 +/- 9% of total chromatographic radioactivity. In 11 DPH-treated rats [125I]T3 increased (p < 0.001) and [125I]T4 decreased (p < 0.02). The DPH effect was blocked in rats treated for 2 days with iopanoic acid 10 mg/100 g BW, though blocking was not seen in rats treated with half the dose of iopanoic acid. In normal rats receiving supplemental doses of T4 (2 micrograms/100 g BW/day for 8 days), DPH similarly increased pituitary 5'-deiodination. Administration of propylthiouracil (PTU) to T4-supplemented rats had no effect on pituitary 5'-deiodination of T4, whereas the addition of DPH to PTU treatment increased [125I]T3 production (p < 0.01). Serum T4 (p < 0.001) and T3 (p < 0.01) were decreased after DPH therapy, while serum and pituitary TSH were not altered.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
14.
目的探讨大鼠脑出血后蛋白激酶C同工酶表达及细胞凋亡程度,以及水蛭素对二者的影响。方法采用未抗凝新鲜自体股动脉血注入大鼠尾状核建立脑出血动物模型,75只大鼠随机分为对照组、脑出血组及水蛭素组。用免疫组织化学法及原位末端标记法分别测定脑出血后6 h、1天、3天、6天、10天等时间点血肿周围组织蛋白激酶C同工酶的表达和细胞凋亡程度,以及水蛭素对二者的影响。结果与对照组比较,血肿周围组织中蛋白激酶C同工酶水平及凋亡细胞数在脑出血后6 h升高(P<0.05),第3天达高峰(P<0.001),此后下降,10天时的表达接近正常,差异无显著性(P>0.05);水蛭素能够降低各个时间点蛋白激酶C同工酶水平及凋亡细胞的表达。结论脑出血后血肿周围蛋白激酶C同工酶水平及凋亡细胞的表达均上调,而水蛭素能够抑制细胞凋亡,其机制可能与抑制蛋白激酶C同工酶的表达有关。 相似文献
15.
E Schlenker 《Respiration physiology》1999,116(2-3):133-143
This study evaluated the effect of microinjection of the non-N-methyl-D-aspartate (NMDA) receptor antagonist, cyano, 3-dihydro-7-nitrogluinoxaline-2, 3-dione (CNQX), into the arcuate nucleus of the hypothalamus on ventilation in male and female rats. Conscious rats received saline or 50, 100, or 200 pmol concentrations of CNQX on separate days. Significant interactions between dose and gender were observed on frequency, inspiratory (TI) and expiratory (TE) time, and tidal volume. CNQX depressed frequency, but increased tidal volume in female rats. Effects of CNQX in males on these ventilatory parameters were considerably less. In CNQX-treated females the decrease in frequency of breathing was primarily due to an increase in TI. Exposure of CNQX-treated female rats to hypercapnia, but not to hypoxia transiently decreased TI. No effect of CNQX was noted on oxygen consumption or body temperature. Thus, non-NMDA receptors in the arcuate nucleus are involved in modulating ventilatory patterns in a gender-specific manner independent of its effects on oxygen consumption or body temperature. 相似文献
16.
Huber R Ditfurth AV Amann F Güthlin C Rostock M Trittler R Kümmerer K Merfort I 《Journal of clinical gastroenterology》2007,41(9):834-838
BACKGROUND: Tormentil extracts (TE) have antioxidative properties and are used as a complementary therapy for chronic inflammatory bowel disease. In individual patients with ulcerative colitis (UC) positive effects have been observed. GOALS: To assess the safety, pharmacology, and clinical effects of different doses of TE in patients with active UC. STUDY: Sixteen patients with active UC [clinical activity index (CAI) >/=5] received TE in escalating doses of 1200, 1800, 2400 and 3000 mg/d for 3 weeks each. Each treatment phase was followed by a 4-week washout phase. The outcome parameters were side effects, CAI, C-reactive protein, and tannin levels in patient sera. RESULTS: Mild upper abdominal discomfort was experienced by 6 patients (38%), but did not require discontinuation of the medication. During therapy with 2400 mg TE per day, median CAI and C-reactive protein improved from 8 (6 to 10.75) and 8 (3 to 17.75) mg/L at baseline to 4.5 (1.75 to 6) and 3 (3 to 6) mg/L, respectively. During therapy, the CAI decreased in all patients, whereas it increased during the washout phase. Neither undegraded nor metabolized tannins could be detected by liquid-mass spectrometry (LC-MS) in patient sera. CONCLUSIONS: TE appeared safe up to 3000 mg/d. Tannins from TE are not systemically absorbed. The efficacy in patients with UC should be further evaluated. 相似文献
17.
Regression of Chronic Hypoxia-Induced Pulmonary Hypertension, Right Ventricular Hypertrophy, and Fibrosis: Effect of Enalapril 总被引:6,自引:0,他引:6
V. Pelouch F. Kolář B. Ošt'ádal M. Milerová R. Čihák J. Widimský 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1997,11(2):177-185
Chronic hypoxia induces pulmonary hypertension and right ventricular hypertrophy. These changes are completely reversible, except for persistent myocardial fibrosis. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can reduce the ventricular collagen content in animals recovering from chronic hypoxia. Adult male Wistar rats were exposed to intermittent high-altitude hypoxia simulated in a barochamber (7000 m, 8 hr/day, 5 days a week, 24 exposures), then transferred to normoxia and divided into two groups: (a) treated with enalapril (0.1 g/kg/day for 60 days) and (b) without treatment. The corresponding control groups were kept under normoxic conditions. Enalapril significantly decreased the heart rate, systemic arterial pressure, and absolute left and right ventricular weights in both hypoxic and control rats; on the other hand, the pulmonary blood pressure was unchanged. The content and concentration of collagen was reduced in both ventricles of enalapril-treated hypoxic and control animals by 10–26% compared with the corresponding untreated groups. These data suggest that the partial regression of cardiac fibrosis due to enalapril may be independent of the pressure load. 相似文献
18.
目的 观察脑出血大鼠脑血肿周围组织细胞凋亡及其与胱冬酶-3和程序性细胞死亡分子-5(programmed cell death-5,PDCD-5)蛋白表达之间的关系,探讨脑出血后的损伤机制.方法 54只雄性wistar大鼠,随机分为假手术组和脑出血组,后者又分为3 h、6 h、12 h、1 d、2 d、3 d、5 d和7 d等8个亚组,每组6只.自体尾动脉不凝血50μl注入尾状核区建立脑出血模型,TUNEL法检测细胞凋亡,免疫组化法观察胱冬酶-3和PDCD-5蛋白表达.结果 脑出血大鼠血肿周围组织3 h出现凋亡细胞,2~3 d达高峰,3 d后凋亡细胞数量开始下降.血肿周围组织3 h可见胱冬酶-3和PDCD-5蛋白阳性细胞,1~2 d达高峰,3 d后逐渐减少.脑出血大鼠血肿周围组织胱冬酶-3(r=0.971,P<0.01)和PDCD-5(r=0.334,P<0.01)阳性细胞数量与凋亡细胞数量呈正相关.结论 脑出血大鼠血肿周围组织存在细胞凋亡,且与胱冬酶-3和PDCD-5蛋白表达一致,胱冬酶-3和PDCD-5蛋白可能促进脑出血后血肿周围组织细胞凋亡. 相似文献
19.
Effects of thyroxine on oestrogen receptor concentrations in anterior pituitary and hypothalamus of hypothyroid rats 总被引:1,自引:0,他引:1
L R Altschuler J A Ceppi M N Ritta R S Calandra A A Zaninovich 《The Journal of endocrinology》1988,119(3):383-387
The effects of thyroxine (T4) were studied on the concentration of oestrogen receptors in the anterior pituitary gland and hypothalamus of ovariectomized euthyroid and hypothyroid rats. A group of rats was made hypothyroid by the administration of 131I. Seven days after ovariectomy, animals were separated into five groups: I, euthyroid controls; II, hypothyroid controls; III, hypothyroid and injected with oestradiol benzoate (10 micrograms/day for 10 days); IV, hypothyroid and injected with T4 (4 micrograms/day for 10 days) and V, hypothyroid and injected with both oestradiol and T4 as described above. In group I, oestrogen receptor levels in pituitary cytosol were 44.4 +/- 3.4 (S.D.) fmol/mg protein and in the nucleus 47.7 +/- 4.0 fmol/mg DNA. In group II the respective values were 12.8 +/- 1.7 fmol/mg protein (P less than 0.01) and 12.7 +/- 1.7 fmol/mg DNA (P less than 0.01 compared with group I). In group III, cytosolic receptor concentrations decreased when compared with those in group II (P less than 0.05), whereas nuclear receptor concentrations rose significantly (P less than 0.01). Group IV had both pituitary cytosolic and nuclear receptors increased (P less than 0.01 compared with group II). In group V there were no changes in cytosolic receptor concentrations but a significant (P less than 0.01) rise in nuclear receptors as compared with group II. Hypothalamic oestrogen receptors in untreated hypothyroid rats (group II) were unchanged in the cytosol and diminished (P less than 0.01) in the nucleus in relation to euthyroid controls (group I). Thyroxine, but not oestrogen, was effective in increasing the concentration of cytosolic receptors (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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3-硝基丙酸预处理对大鼠局灶性脑缺血caspase-3活性和神经细胞凋亡的影响 总被引:2,自引:0,他引:2
目的 探讨小剂量线粒体毒素3-硝基丙酸(3-NPA)预处理对大鼠局灶性脑缺血脑梗死体积、脑缺血半暗带半胱天冬酶一3(caspase-3)活性和神经细胞凋亡的影响。方法 大鼠腹腔注射3-NPA 3d后制作大脑中动脉闭塞模型,采用TTC染色、TuNEL法、流式细胞术和荧光测定法,观察3-NPA预处理对缺血2h再灌注24h脑梗死体积、神经细胞凋亡和caspase-3活性的影响。结果 缺血2h再灌注24h,3-NPA预处理组脑梗死体积减小22.3%,caspase-3活性降低13.9%,TUNEL阳性细胞数和细胞凋亡百分率分别减少47.0%和43.9%,与对照组比较差异有显著性。结论 3-NPA预处理可以诱导脑缺血耐受,降低caspase-3活性,抑制神经细胞凋亡可能是其机制之一。 相似文献