钙调神经磷酸酶在肾血管性高血压大鼠心肌肥厚发展中的作用

本文观察了钙调神经磷酸酶(calcineurin,CaN)在肾血管性高血压大鼠肥厚心肌中的表达和活性以及CaN抑制剂——环孢菌素A(cyclosporine A,CsA)对逆转心肌肥厚的影响。利用两肾一夹肾血管性高血压大鼠心肌肥厚模型,观察大鼠心肌肥厚程度、CaN mRNA和蛋白质表达及CaN活性的改变。结果显示:大鼠左室重与胫骨长度的比值和光镜下心肌细胞横截面积在两肾一夹2月和3月组都较相应假手术组增高(P<0.05),CsA组大鼠左室重与胫骨长度比值、心肌细胞横截面积较两肾一夹2月和3月组均显著下降(P<0.05),与假手术组无显著性差异。大鼠心肌CaN mRNA和蛋白质表达及CaN活性在两肾一夹2月和3月组均高于相应假手术组(P<0.05),在CsA组低于两肾一夹2月和3月组(P<0.05)。这些结果提示,CaN参与肾血管性高血压大鼠心肌肥厚发展,抑制CaN活性可逆转心肌肥厚。     

Potential role of kinins in the effects of taurine in high-fructose-fed rats

The present work investigates the involvement of kinins in the effects of taurine in fructose-fed hypertensive rats. The effects of taurine on blood pressure, plasma glucose, insulin, and the insulin sensitivity index were determined. Angiotensin-converting enzyme (ACE) activity and nitrite content in plasma, plasma and tissue kallikrein activity, and taurine content were also investigated. The blood pressure changes in response to the coadministration of inhibitors of the synthesis of nitric oxide (NO), prostaglandins (PGs), or a kinin receptor blocker along with taurine was also evaluated. Fructose-fed rats had higher blood pressure and elevated plasma levels of glucose and insulin. Kallikrein activity, taurine, and nitrite contents were significantly lower in fructose-fed rats as compared with controls. The increases in systolic blood pressure, hyperglycemia, and hyperinsulinemia were controlled by taurine administration in fructose-fed rats. ACE activity was lower, while nitrite and taurine content and kallikrein activity were higher, in taurine-supplemented rats as compared with fructose-fed rats. A significant increase in blood pressure was observed in rats cotreated with the inhibitors Hoe 140 (a kinin receptor blocker), L-NAME (a NO synthase inhibitor), or indomethacin (a PG synthesis inhibitor) with taurine for 1 week as compared with taurine-treated fructose-fed rats. This suggests that the antihypertensive effect of taurine in fructose-fed rats was blocked by the inhibitors. Augmented kallikrein activity and, hence, increased kinin availability may be implicated in the effects of taurine in fructose-fed hypertensive rats.     

Role of spermatogonia in the stage-synchronization of the seminiferous epithelium in vitamin-A-deficient rats

After 20-day-old rats are placed on a vitamin-A-deficient diet (VAD) for a period of 10 weeks, the seminiferous tubules are found to contain only Sertoli cells and a small number of spermatogonia and spermatocytes. Retinol administration to VAD rats reinitiates spermatogenesis, but a stage-synchronization of the seminiferous epithelium throughout the testis of these rats is observed. In order to determine which cell type is responsible for this synchronization, the germ cell population has been analyzed in whole mounts of seminiferous tubules dissected from the testes of rats submitted to the following treatments. Twenty-day-old rats received a VAD diet for 10 weeks and then were divided into three groups of six rats. In group 1, all animals were sacrificed immediately; in group 2, the rats were injected once with retinol and sacrificed 3 hr later; in group 3, the rats were injected once with retinol, placed on a retinol-containing diet for 7 days and 3 hr, and then sacrificed. Three rats from each group had one testis injected with 3H-thymidine 3 hr (groups 1 and 2) or 7 days and 3 hr (group 3) before sacrifice. Three normal adult rats (approximately 100 days old) served as controls. Labeled and unlabeled germinal cells were mapped and scored in isolated seminiferous tubules. In group 1, type A1 and type A0 spermatogonia as well as some preleptotene spermatocytes were present; type A2, A3, A4, In, and B spermatogonia were completely eliminated from the testis. Neither type A1 mitotic figures nor 3H-thymidine-labeled-type A1 nuclei were seen.(ABSTRACT TRUNCATED AT 250 WORDS)     

The biology of NippostrongyLus brasiliensis in SPF rats

When maintained under SPF (specific pathogen free) conditions, Wistar rats had low and variable counts of adult Nippostrongylus brasiliensis. Worm counts were increased if rats were kept in solid rather than wire-bottom cages, if rats were maintained under non-SPF conditions, or if SPF rats were orally inoculated with gut contents from non-SPF rats. It is concluded that gut flora in SPF wistar rats directly or indirectly affects the numbers of larvae establishing as adult worms.     

Persistence of sialodacryoadenitis virus in athymic rats

To determine whether SDAV infection persists in athymic rats, weanling athymic rats and euthymic rats were inoculated intranasally with 10(4) TCID50 of SDAV and examined periodically for up to 90 days. Viral antigen and lesions characteristic of acute SDAV infection, including rhinotracheitis, bronchitis and sialodacryoadenitis, were detected in both groups of rats during the first week. In euthymic rats, tissues were under repair and viral antigen was undetectable by day 17, and tissues were histologically normal by day 31 except for mild focal dacryoadenitis. In athymic rats, viral antigen and chronic active inflammation of respiratory tract, salivary and lacrimal glands persisted through day 90. Inflammation and viral antigen also were observed in the transitional epithelium of the renal pelvis and urinary bladder as late as day 90. Virus was isolated from nasopharynx, lung, salivary gland and Harderian gland of athymic rats through day 90. All euthymic rats seroconverted to SDAV by day 6, whereas all athymic rats remained seronegative through day 31, and two of six were seropositive by day 90. As judged by seroconversion of contact sentinels, six of six athymic rats shed virus through 6 weeks, and five of six through 10 weeks. These results indicate that SDAV persists in athymic rats, and that normal T cell function is required for host defenses against SDAV.     

Aging Contributes to Inflammation in Upper Extremity Tendons and Declines in Forelimb Agility in a Rat Model of Upper Extremity Overuse

We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.     

Influence of diet form on the hyperphagia-promoting effect of polysaccharide in rats

Adult female rats were fed chow only, or chow plus the polysaccharide Polycose presented as a solution (32% w/v), as a powder, or as a powder mixed into the chow diet. The rats fed the Polycose solution overate and gained three times as much weight as did the control rats in the 30-day test period. The rats fed the Polycose powder or mixed diet, on the other hand, did not differ from controls in food intake or weight gain. The solution-fed rats consumed more Polycose than did the powder-fed rats, but the two groups were equivalent in their chow intake. The absolute and percent body fat of the solution-fed rats exceeded that of control rats, as well as that of powder and mixed-diet animals. The percent body fat of the powder and mixed diet groups exceeded that of the control animals. The findings demonstrate that the form of diet presentation has a major impact on the rat's feeding and body weight responses to polysaccharide diets.     

Investigation of oxidative stress during fracture healing in the rats

One of the most damaging effects of reactive oxygen species (ROS) is lipid peroxidation, the end-product of which is malondialdehyde (MDA). This study was aimed to evaluate erythrocyte MDA levels during fracture healing in rats. Thirty male rats were used and the rats were divided into two groups to serve as controls and tests. Six rats were used as a control group that was not subject to fracture. The remaining 24 rats were divided into four groups and erythrocyte MDA levels were examined on days 5, 10, 20 and 30 post fracture. The right fibulas of rats were broken by manual angulation in the experimental group. The erythrocyte malondialdehyde level was measured in the experimental and control groups. The difference between malondialdehyde levels of control and experimental groups was statistically significant (p<0.05). Oxidative stress clearly increases during fracture healing in rats.     

Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.     

Features of active control used in pharmacological studies

The effects of 5 injections of salt solution and unfractionary heparin in dose 0.36 microgram/kg (Serva, Germany 10 kDa, activity 180 U/mg) have been studied in Wistar rats. It was found that two injections of salt solution were enough to form a stable defensive state in all rats which was manifested as an expectation of pain in tail-flick testing. The defensive motivation provoked by the injections negatively influenced the learning process as saline-induced rats refused to solve a food-getting task in a problem situation. Explorative and locomotor activities were depressed in these rats and were accompanied by numerous stressful and neurotic-like manifestations. Unlike saline-rats, practically all heparinized-rats instead of 45% of intact rats were able to solve a cognitive task despite the injections. Anxiety was decreased, but sensitivity to different external factors was increased in the heparin-induced rats. Formed habit in these rats was characterized by a high organization and stability. However, the majority heparin effects in tail-flick test were discovered when comparing the heparin-induced rats with intact ones and were not observed in comparison with the saline-rats. It is suggested that the saline-control should be considered as specific control having defensive features which are necessary to take into account in interpretation of effects of other pharmacological preparations.     

Characterization of Oxidative Stress in Various Tissues of Diabetic and Galactose-fed Rats

Rats fed a galactose-rich diet have been used for several years as a model for diabetes to study, particularly in the eye, the effects of excess blood hexoses. This study sought to determine the utility of galactosemia as a model for oxidative stress in extraocular tissues by examining biomarkers of oxidative stress in galactose-fed rats and experimentally-induced diabetic rats. Sprague-Dawley rats were divided into four groups: experimental control; streptozotocin-induced diabetic; insulin-treated diabetic; and galactose-fed. The rats were maintained on these regimens for 30 days, at which point the activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase, as well as levels of lipid peroxidation and reduced and oxidized glutathione were determined in heart, liver, and kidney. This study indicates that while there are some similarities between galactosemic and diabetic rats in these measured indices of oxidative stress (hepatic catalase activity levels and hepatic and renal levels of oxidized glutathione in both diabetic and galactosemic rats were significantly decreased when compared to normal), overall the galactosemic rat model is not closely parallel to the diabetic rat model in extra-ocular tissues. In addition, several effects of diabetes (increased hepatic glutathione peroxidase activity, increased superoxide dismutase activity in kidney and heart, decreased renal and increased cardiac catalase activity) were not mimicked in galactosemic rats, and glutathione concentration in both liver and heart was affected in opposite ways in diabetic rats and galactose- fed rats. Insulin treatment reversed/prevented the activity changes in renal and cardiac superoxide dismutase, renal and cardiac catalase, and hepatic glutathione peroxidase as well as the hepatic changes in lipid peroxidation and reduced and oxidized glutathione, and the increase in cardiac glutathione. Thus, prudence should be exercised in the use of experimentally galactosemic rats as a model for diabetes until the correspondence of the models has been more fully characterized.     

Inhibition of mammary tumorigenesis in virgin rats by adoptive transfer of splenocytes from parous donors

Summary Splenocytes from parous rats have been previously found to have cytotoxic activity against mammary tumor cells in vitro. Experiments were carried out to determine if this pregnancy-induced cytotoxic nature of the splenocytes is inherent and transferable. Splenocytes from parous rats were adoptively transferred to a group of virgin rats. Another group of age-matched, virgin rats received splenocytes from virgin donors in a similar way. After a period of rest, at the age of 55 days, the rats belonging to both of the groups, received 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. A third group of untreated virgin rats were also given the chemical carcinogen the same way as above and were considered as intact controls. The rats were monitored for development and growth of mammary tumor from 60 days of DMBA administration. After 4 months of DMBA administration the rats were sacrificed and mammary glands were examined for tumors. Mammary glands with no visible tumors were taken for whole mount preparation, to be examined for microscopic lesions. The results showed that 33 of 41 intact control rats, developed tumor and 27 of the 34 rats that received spleen cells from virgin rats developed tumors. Of the rats that received spleen cells from parous rats, only 18 out of 37 rats developed tumors, indicating an inhibition of tumor induction in these rats. Growth rate of the tumors in this group was also slower than in the control groups.This research was supported by USPHS grant CA 3613906 awarded by the National Cancer Institute     

Sympathetic Regulation of Circadian Rhythm of Serotonin N-Acetyltransferase Activity in Pineal Gland of Infant Rat

Abstract: The circadian rhythms of serotonin N -acetyltransferase activity in the pineal glands of infant and adult rats were compared. The nighttime increase of N -acetyltransferase activity in the pineals of infant rats was blocked by removal of superior cervical ganglion or by pretreatment with reserpine, l -propranolol, and cycloheximide. Injection of isoproterenol to infant rats markedly elevated pineal N -acetyltransferase activity. When the pineal glands of infant rats were organ-cultured, N -acetyltransferase activity spontaneously increased 7–12 h after the rats were killed. When infant rats were previously denervated or pretreated with reserpine and their pineals were cultured, this spontaneous elevation of N -acetyltransferase activity was abolished, indicating that the transient increase of the enzyme activity in organ culture was due to a liberation of catecholamine from degenerating nerve endings. Additional illumination until midnight prevented the nighttime increase of N -acetyltransferase activity in intact infant rats but not in blinded infant rats. These observations are taken to indicate that N -acetyltransferase rhythm in immature rat pineals is regulated by the sympathetic nerves in the same manner as in adult rat pineals, that the immature rat pineal does not contain a time-keeping system, and that there is no extraretinal light perception in infant rats as far as N -acetyltransferase rhythm is concerned.     

Effect of ethanol administration on metabolism of lipids in heart and aorta in isoproterenol induced myocardial infarction in rats

Effect of ethanol administration on the severity of myocardial infarction induced by isoproterenol in rats was studied. Even though serum CPK and GOT levels as well as the extent of myocardial damage as revealed by histopathological studies, were similar, the survival rate was higher in rats administered ethanol. Concentration of cholesterol and triglycerides in the serum and heart in rats given ethanol and isoproterenol seems to be the additive effect caused individually by ethanol and isoproterenol. Myocardial alcohol dehydrogenase and aldehyde dehydrogenase both showed increased activity in rats treated with ethanol. The rate of recovery from myocardial infarction however, was slower in rats treated with ethanol as judged from the serum CPK value.     

Studies of 5'-deiodinase activity in rats differing in hepatic lipogenic activity

Studies of the relationship of hepatic 5'-deiodinase activity to hepatic lipogenic capacity were conducted. Rats of the Zucker, BHE, and Sprague-Dawley strains were used. BHE and Sprague-Dawley rats were starved and refed a 65% glucose diet, whereas lean and obese Zucker rats were fed a stock diet; the rats were thus different in hepatic lipogenic capacity. After hepatic 5'-deiodinase activity was determined, we found that rats genetically predisposed to increased hepatic lipogenesis had less deiodinase activity than rats without this genetic feature. The role of the interaction between the thyroid hormones and glucocorticoid in the activity of hepatic deiodinase was also studied. Adrenalectomized (ADX) or intact BHE and Sprague-Dawley rats were injected with saline, thyroxine, or triiodothyronine and either saline or glucocorticoid. The normal Sprague-Dawley rats made predictable adjustments to their deiodinase activity when their hormonal status was manipulated, whereas the BHE rats responded as though these manipulations were corrections rather than additions or deletions.     

Effect of glycine in streptozotocin-induced diabetic rats

Inadequate utilization of glucose in diabetes mellitus favors diverse metabolic alterations that play a relevant role in the physio-pathology of chronic complications of this disease. Streptozotocin-induced diabetic rats were treated daily with glycine (130 mM as optimal concentration) or taurine (40 mM) for six months. Groups of diabetic rats without treatment were used as controls. Glucose, total cholesterol, triacylglycerol, and glycated hemoglobin were determined periodically after inducing diabetes. Rats were killed after 6 months of treatment and histological analyses were performed. Diabetic groups that received glycine or taurine showed significant lower concentrations of glucose, total cholesterol, triacylglycerol, and glycated hemoglobin than diabetic control rats (P<0.05) after 6 months treatment. Histological analyses of diabetic rats showed pancreatic atrophy and necrosis, vacuolization, decrease of beta cells, and diffuse glomerulosclerosis. Diabetic rats treated with glycine or taurine showed less enlargement of the glomerular basal membrane than control diabetic rats. Our results suggest that glycine and taurine reduced the alterations induced by hyperglycemia in streptozotocin-induced diabetic rats probably due to inhibition of oxidative processes.     

Decreased ketonaemia in the monosodium glutamate-induced obese rats

Plasma concentrations of total ketone bodies, acetoacetate (AcAc) and 3-hydroxybutyrate (3-OHBA) in monosodium glutamate (MSG)-induced obese rats were measured. MSG-treated rats showed higher Lee's indices, shorter naso-anal and tail length, and a more marked intraperitoneal fat deposition than control rats. Plasma concentrations of glucose, free fatty acid, triglyceride and phospholipids were significantly increased in the MSG-treated rats as compared to the control rats (24 weeks-old). Plasma levels of total ketone bodies, AcAc and 3-OHBA were all decreased in the MSG-treated rats as compared to control rats. The ratio, 3-OHBA/AcAc in the MSG-treated rats were not different from those in the control rats.     

Occurrence of Yersinia enterocolitica in house rats.

From July 1976 to May 1977, 270 rats (259 Rattus norvegicus and R. rattus) in Sapporo were examined for the presence of Yersinia enterocolitica in house rats. The organism was isolated in 55 rats (54 R. norvegicus and 1 R. rattus). Isolated strains were determined as O group (O)3, biovar 4; O4, biovar 1; O5A, biovar 1; and O6, biovar 1. The isolation of O3, biovar 4 strains from R. norvegicus is the first in the world, as far as we know. The organism was isolated from the duodenum in 3 rats, the jejunum in 7 rats, the ileum in 8 rats, the cecum in 34 rats, the colon in 23 rats, the rectum in 16 rats, and the mesenteric lymph nodes in 5 rats. The organism was not isolated from liver, spleen, and kidneys. Isolation of the organism from the mesenteric lymph nodes was made in 1 out of 2 O3-positive rats, 1 out of 7 O5A-positive ones, and 3 out of 29 O6-positive ones. A high agglutinin titer was recorded in the two O3-positive rats and in one O6-positive animal.     

Changes in rhythmicities of ambulatory and drinking activities after hypophysectomy in rats.

Effects of hypophysectomy on circadian rhythms of ambulatory and drinking activities in adult male rats were automatically recorded and investigated with a Gundai-type ambulodrinkometer. The rats were maintained under LL conditions following an LD condition. When free-running rhythms had stabilized, the rats were hypophysectomized. The rhythmicities of both activities became indistinct over the 2-4 weeks following surgery, and then gradually recovered. At this time phase shifts (phase advance) were observed in the hypophysectomized rats, while these changes were not observed in sham-operated rats. All rats entrained to lighting when kept under LD conditions again. These results suggest that the pituitary does not play an essential role in maintaining circadian rhythms, but does function as an important subordinal oscillator.     

Downregulation of prolactin-releasing peptide gene expression in the hypothalamus and brainstem of diabetic rats

We investigated the prolactin-releasing peptide (PrRP) mRNA levels in the hypothalamus and brainstem of streptozotocin (STZ)-induced diabetic rats and fa/fa Zucker diabetic rats, using in situ hybridization histochemistry. PrRP mRNA levels in the hypothalamus and brainstem of STZ-induced diabetic rats were significantly reduced in comparison with those of control rats. PrRP mRNA levels in the diabetic rats were reversed by both insulin and leptin. PrRP mRNA levels in the fa/fa diabetic rats were significantly reduced in comparison with those of Fa/? rats. PrRP mRNA levels in the fa/fa diabetic rats were significantly increased by insulin-treatment, but did not reach control levels in the Fa/? rats. We also investigated the effect of restraint stress on PrRP mRNA levels in STZ-induced diabetic rats. The PrRP mRNA levels in the control and the STZ-induced diabetic rats increased significantly after restraint stress. The diabetic condition and insulin-treatment may affect the regulation of PrRP gene expression via leptin and other factors, such as plasma glucose level. The diabetic condition may not impair the role of PrRP as a stress mediator.