Dietary sodium restriction and the development of two-kidney, one-clip hypertension in young versus adult rats.

To determine the effects of moderate versus severe dietary sodium restriction on the development of 2-kidney, 1-clip (2K,1C) hypertension, young male Wistar rats were placed on diets containing 9, 26, or 101 (control) mumol sodium/g food. Three days later, a solid silver clip (i.d. 0.20 mm) was placed on the left renal artery and diets were continued up to 6 weeks. Adult rats received a 0.25-mm clip. In young clipped rats receiving the 101 mumol/g diet, blood pressure (BP), plasma renin activity (PRA), and BP response to captopril were increased as early as 1 week after clipping and increased further over time. Moderate sodium restriction (26 mumol sodium/g) led to only a slight delay in the development of hypertension; the levels of BP and PRA, the BP response to captopril, and the extent of cardiac hypertrophy achieved by 6 weeks were not different between the 2K, 1C rats receiving 26 or 101 mumol sodium/g. Sodium restriction to 9 mumol/g decreased rate of growth and completely prevented the rise in BP and in left ventricular weight. At 3 and 6 weeks the severely sodium-restricted rats had significantly higher PRA levels than the 2K, 1C control group. However, the BP response to captopril was attenuated relative to the other hypertensive groups. In adult rats, this level of sodium restriction had a small, but significant effect on body weight, but still prevented the increase in BP and in left ventricular weight. In conclusion, dietary sodium restriction can prevent the development of 2K,1C hypertension in both young and adult rats, but only if the restriction is severe. This effect may relate to a marked reduction in the pressor effectiveness of the renin-angiotensin system by low sodium intake per se or by associated metabolic or other changes.     

Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats

ABSTRACT: BACKGROUND: Astaxanthin (ASTA) is a fat-soluble xanthophyll with powerful antioxidant functions. It is extracted from e.g. salmon, an important food source for certain human populations known to have a reduced risk of tumor development. It is possible that ASTA plays a role in cancer chemoprevention in such populations. The purpose of this study was to investigate the effects of dietary ASTA on chemically induced mammary tumorigenesis using N-methyl-N-nitroso-urea (MNU) in immature Wistar rats. METHODS: Thirty-six 37 days old juvenile female Wistar rats were at random allocated to 4 groups of which Groups 1 and 2 received a single dose of 55 mg MNU/kg body weight. The effects of ASTA was evaluated by giving rats of Groups 2 and 4 a dose of 50 mg ASTA/kg/day for the entire duration of the study. Group 3 rats received feed added alimentary oil.Necropsy and histopathological examinations were carried out on each rat 14 months after the administration of MNU. Haematological values and antioxidative status were determined. Oxidative stress was evaluated by monitoring superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in hepatic tissue. Lipid peroxidation and carbonylation of proteins was determined in protein extracts from the liver. RESULTS: Tumor development occurred only in rats of Groups 1 and 2, i.e. MNU exposed animals. Frequency of tumor development in general and average number of tumors per animal were insignificant between these two groups. Mammary gland tumors developed in equal frequencies in Group 1 and 2 rats, respectively. Although only rather few tumors were found in the mammary glands, a substantial number of other tumors were found in Group 1 and 2 rats, but at equal rates.Biochemical analyses showed significant higher levels of GPx, malondialdehyde and dinitrophenylhydrazine in Group 1 rats that for rats in all other groups thus indicating protective effects of ASTA on MNU induced hepatic oxidative stress. CONCLUSIONS: Supplementation with ASTA did not reduce tumorigenesis induced by MNU in Wistar rats. However, supplementation with ASTA seemed to have anti-inflammatory effects.     

Activity of Porphyridium sp. polysaccharide against herpes simplex viruses in vitro and in vivo.

The cell wall sulfated polysaccharide of the red microalga Porphyridium sp. exhibited impressive antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and -2) both in vitro (cell culture) and in vivo (rats and rabbits). Depending on the concentration, this polysaccharide completely inhibited or slowed down the development of the cytopathic effect in HSV-infected cells, but did not show any cytotoxic effects on vero cells even when a concentration as high as 250 μg/ml was used. There was indirect evidence for a strong interaction between the polysaccharide and HSV and a weak interaction with the cell surface. When tested in vivo, Porphyridium sp. polysaccharide conferred significant and efficient protection against HSV-1 infection: at a concentration as low as 100 μg/ml, it prevented the appearance and development of symptoms of HSV-1 infection in rats and rabbits. The polysaccharide did not exhibit any cytotoxic effects at a concentration of 2 mg/ml in vivo.     

Dietary conjugated linoleic acid has limited effects on tissue protein anabolism in sedentary and exercising adult rats

The effects of conjugated linoleic acid isomers (CLA) and endurance training on lean body mass are expected to result from their action on tissue protein metabolism. The aim of this study was to analyze their effects on protein metabolism in 2 muscles, the small intestine and liver of adult rats. Four-month-old male Wistar rats were fed diets containing either no CLA, cis-9, trans-11 CLA isomer (1 g.100 g(-1)), trans-10, cis-12 CLA isomer (1 g.100 g(-1)) or both isomers (1 g.100 g(-1) each) for 6 weeks. Half of the rats were subjected to endurance training by running on a treadmill. At the end of this period, the rats were injected with a flooding dose of (13)C-valine to determine protein synthesis rates in the post-absorptive (experiment 1) and in the post-prandial (experiment 2) states. No effect of CLA or endurance training were detected in the small intestine. Training reduced food intake and protein synthesis rates in the liver but no effect was found on the protein synthesis rates in muscles. In the post-absorptive state, protein synthesis rate was increased by feeding the trans-10, cis-12 CLA isomer alone in the liver (+9%) or in combination with the cis-9, trans-11 isomer in the gastrocnemius (+30%), mostly in sedentary rats. In the post-prandial state, the cis-9, trans-11 CLA isomer tended to reduce the protein synthesis rate in the gastrocnemius muscle. However, no effect of CLA was found on muscle protein amounts. In conclusion, CLA isomers would have limited but differential effects on tissue protein metabolism in adult rats.     

The display of sexual behaviors by female rats administered ICI 182,780

ICI 182,780 (ICI) is a pure antiestrogen that when administered systemically does not cross the blood-brain barrier, thus its actions are limited to the periphery. Four experiments were conducted to test the effects of ICI on the display of sexual behaviors in ovariectomized rats. Experiment 1 examined the effects of three doses of ICI (250, 500, and 750 μg/rat) on sexual receptivity and paced mating behavior in rats primed with estradiol benzoate (EB) in combination with progesterone (P). Experiments 2 and 3 compared the display of sexual behaviors in rats primed with EB+P or EB alone and administered either 250 μg ICI (Experiment 2) or 500 μg ICI (Experiment 3). Experiment 4 tested the effects of ICI (250 and 500 μg) on the expression of estrogen-induced progestin receptors in the uterus. ICI did not affect the display of sexual receptivity in any experiment. In rats primed with EB+P, paced mating behavior was altered by the 500 and 750 μg, but not the 250 μg, doses of ICI. The lowest (250 μg) dose of ICI did alter paced mating behavior in rats primed with EB alone. The effects of ICI on paced mating behavior were manifested by a substantial lengthening of contact-return latencies following intromissions and ejaculations. The percentage of exits were not affected by ICI. Estrogen stimulation of uterine weight and induction of uterine progestin receptors was suppressed by ICI (250 and 500 μg). ICI effects on paced mating behavior in hormone-primed female rats are likely to reflect antiestrogenic actions in the periphery, including interference with the estrogen induction of progestin receptors.     

Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides.

Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long-lasting increase of the low-affinity dopamine (DA) uptake capacity in S1-fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress.     

Hexavalent chromium effects on motor activity and some metabolic aspects of Wistar albino rats

The effects of hexavalent chromium on the motor activity and some metabolic aspects of albino rats were studied. 0.07 g Cr(VI)/l administered in drinking water produced no effects on the motor activity of rats, at least over 28 days of treatment. 0.7 g Cr(VI)/l in drinking water and 2 mg Cr(VI)/kg body wt injected i.p. significantly decreased the motor activity of rats after 7 days and 1 day, respectively. The treated rats showed a metabolic disadvantage in relation to the controls. The effects caused by Cr(VI) on the motor activity in rats could be an indication of the neurotoxicity of this metal.     

1,25(OH)2D3 alters growth plate maturation and bone architecture in young rats with normal renal function

Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH)(2)D(3), the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH)(2)D(3) is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD) and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH)(2)D(3) treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 μg/kg 1,25(OH)(2)D(3) for one week, or intermittent 3 μg/kg 1,25(OH)(2)D(3) for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH)(2)D(3)-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH)(2)D(3) increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25(OH)(2)D(3) lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH)(2)D(3)-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH)(2)D(3) on intracortical bone formation. This study shows negative effects of 1,25(OH)(2)D(3) on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients.     

Effects of high salt intake on brain AT1 receptor densities in Dahl rats

To assess effects of dietary salt on brain AT1 receptor densities, 4-wk-old Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats were fed a regular (101 mumol Na/g) or high (1,370 mumol Na/g)-salt diet for 1, 2, or 4 wk. AT1 receptors were assessed by quantitative in vitro autoradiography. AT1 receptor densities did not differ significantly between strains on the regular salt diet. The high-salt diet for 1 or 2 wk increased AT1 receptor binding by 21-64% in the Dahl S rats in the subfornical organ, median preoptic nucleus, paraventricular nucleus, and suprachiasmatic nucleus. No changes were noted in the Dahl R rats. After 4 wk on a high-salt diet, increases in AT1 receptor binding persisted in Dahl S rats but were now also noted in the paraventricular nucleus, median preoptic nucleus, and suprachiasmatic nucleus of Dahl R rats. At 4 wk on the diet, intracerebroventricular captopril caused clear decreases in blood pressure only in the Dahl S on the high-salt diet but caused largely similar relative increases in brain AT1 receptor densities in Dahl S and R on the high-salt diet versus regular salt diet. These data demonstrate that high salt intake rapidly (within 1 wk) increases AT1 receptor densities in specific brain nuclei in Dahl S and later (by 4 wk) also in Dahl R rats. Because the brain renin-angiotensin system only contributes to salt-induced hypertension in Dahl S rats, further studies are needed to determine which of the salt-induced increases in brain AT1 receptor densities contribute to the hypertension and which to other aspects of body homeostasis.     

Effects of maternal blood loss on embryonic and placental development in the rat.

The effects of acute loss of maternal blood on embryonic and placental development was examined in 50 rats on Days 8 or 9 of gestation. Blood was withdrawn from conscious, cannulated rats over a 1-min period at 1-0 or 2-0 ml/100 g body weight. These degrees of blood loss were expected to produce a mild (about 50%) and severe (about 80%) reduction in uterine blood flow, respectively, for at least 15 min. There was no evidence that loss of blood affected either fetal survival and malformation rates or fetal weights and sex ratios. The anaemia resulting from haemorrhage lasted no longer than 6 days. Placental weights were 11% higher in rats losing 2-0 ml blood/100 g than in controls (P less than 0-05). It appears that the 8- or 9- day rat embryo is highly resistant to the partial reduction in uterine blood flow, maternal anaemia and other possible challenges induced by maternal loss of blood at levels sufficient to affect the mothers.     

Mounting and receptive behavior in the ovariectomized female rat: Influence of estradiol,dihydrotestosterone, and genital anesthetization

Two experiments were performed with ovariectomized female rats in an attempt to determine whether estradiol and dihydrotestosterone work synergistically in the brain to activate mounting behavior. In Expt 1, performed in Göteborg, it was found that females treated daily with 2 μg estradiol benzoate (EB) combined with 500 μg dihydrotestosterone (DHT) displayed significantly more mounts with pelvic thrusting than other females treated with the oil vehicle, 500 μg DHT, or 2 μg EB. The behavior of rats receiving EB + DHT was indistinguishable from that of yet another group of females which received 200 μg testosterone propionate (TP). In Expt 2, performed in Rotterdam, it was found that ovariectomized female rats treated with either 200 μg TP or 2 μg EB + 200 μg dihydrotestosterone propionate (DHTP) mounted significantly more than females treated with 2 μg EB. Both clitoral size and the growth of cornified papillae on the glans clitoris were stimulated by the administration of TP or EB + DHTP. However, in no group was the frequency of mounting affected by anesthetization of the clitoris and external vagina with lidocaine paste. Lordosis quotients of females treated with EB + DHTP were significantly lower than in rats receiving either EB or TP, again regardless of whether or not the genital region was anesthetized. It is concluded that the effects of DHT on estradiol-induced mounting and receptivity most likely result from the action of this androgen on the brain, and not from the stimulatory effect which DHT may exert on genital sensory receptors.     

Development of sensory motor reflexes in 2 G exposed rats

During gestation and early postnatal development, the animal's size and weight rapidly increase. Within that period, gravity affects sensory and motor development. We studied age-dependent modifications of several types of motor reflexes in 5 groups of rats conceived, born and reared in hypergravity (HG; 2 g). These rats were transferred to normal gravity (NG; 1 g) at various postnatal days, and their behavioral reflexes were compared with a control group which was constantly kept under NG. HG induced a retarded development of vestibular dependent reflexes. Other types of motor behavior were not delayed.     

Activation of rat liver branched-chain 2-oxo acid dehydrogenase in vivo by glucagon and adrenaline.

The activity of liver branched-chain 2-oxo acid dehydrogenase complex was measured in rats fed on low-protein diets and given adrenaline, glucagon, insulin or dibutyryl cyclic AMP in vivo. Administration of glucagon or adrenaline (200 micrograms/100 g body wt.) resulted in a 4-fold increase in the percentage of active complex. As with glucagon and adrenaline, treatment of rats with cyclic AMP (5 mg/100 g body wt.) resulted in marked activation of branched-chain 2-oxo acid dehydrogenase. Insulin administration (1 unit/100 g body wt.) also resulted in activation of enzyme; however, these effects were less than those observed with glucagon and adrenaline. In contrast with the results obtained with low-protein-fed rats, administration of adrenaline (200 micrograms/100 g body wt.) to rats fed with an adequate amount of protein resulted in only a modest (14%) increase in the activity of the complex. The extent to which these hormones activate branched-chain 2-oxo acid dehydrogenase appears to be correlated with their ability to stimulate amino acid uptake into liver.     

5-Hydroxytryptamine : A modulator of food composition but not quantity?

After a meal of protein, in contrast to a meal of carbohydrate (CHO) at 1915 hr, rats allowed to choose from high carbohydrate and high protein diets during 2000-2100 hr prefer CHO (1). Thus the hypothesis that this regulation of macronutrient selection involves brain 5-hydroxytryptamine (5-HT) metabolism was tested. Compared to three baseline days during which rats (250- 300g ) consumed 1 g CHO, rats fed tryptophan (TRP, 5-HT precursor; 15 mg in 1 g CHO) selected meals higher in protein concentration (35.4% vs 46.6%, F (1,12) = 20.05, p less than 0.001) from 10% and 60% casein diets during 2000-2100 hr. Associated with the higher protein selection was an elevated brain 5-HT turnover in rats killed 30 minutes after consuming CHO + TRP. Pretreating rats with p-chlorophenylalanine, an inhibitor of TRP hydroxylase, blocked this effect of TRP (36.3% vs 37.0%). Fenfluramine (1 and 2 mg/kg i.p. at 1945 hr), which transiently enhances neuronal 5-HT release, increased the rat's relative preference for protein from 28.8% to 37.5% (2 mg/kg, t = 3.21, p less than 0.025) during 2000-2100 hr. These rats, also exhibited a selective preference for CHO between 3-12 hrs post injection which paralleled the known subsequent depletion of 5-HT by fenfluramine. We conclude that the relative proportion of protein and carbohydrate selected in a meal is controlled, at least in part, by prior food effects on brain 5-HT metabolism.     

Effect of various ACTH analogs on lordosis behavior in the female rat

The effect of ACTH and various related analogs on lordosis behavior in female rats was compared with that produced by α-MSH. Ovariectomized rats received 2 μg estradiol benzoate on Day 1 and Day 3 either 0.1 or 0.2 mg progesterone. Four hours later the females were placed with sexually experienced male rats and the lordosis quotient (LQ) noted. These particular doses of progesterone were chosen because they were sub-maximal and produced a proportion of both nonreceptive (LQ less than 50%) and receptive (LQ greater than 50%) rats. Treatment with 20 μg α-MSH on Day 2 stimulated lordosis in nonreceptive rats but inhibited lordosis in the receptive rats.Of the other peptides tested only ACTH4–10 was as effective as α-MSH in facilitating and inhibiting lordosis behavior. ACTH1–24 and ACTH4–9 also produced both effects. ACTH1–39 and ACTH1–16, on the other hand, had neither effect but were both effective in stimulating and inhibiting lordosis when administered on Days 1, 2 and 3. It is suggested that ACTH4–10 may contain the essential sequence for these facilitatory and inhibitory effects on female sexual receptivity and that elongation of the peptide chain beyond ACTH 1–13 (α-MSH) may decrease this activity.     

Effects of cytidine 5'-diphosphocholine on plasma homocysteine levels in rat

We have investigated the effects of cytidine 5'-diphosphocholine (CDP-choline) on total plasma homocysteine concentration in male Sprague-Dawley rats of 2 months of age (young rats) or 15 months of age (old rats). Oral administration of 0.35 or 1 g/kg of CDP-choline to young rats significantly increased homocysteine, by 19 and 47%, respectively (P<0.05) in plasma obtained 25 min after treatment. This effect was transient for the administration of 0.35 g/kg and increased up to 64% (P<0.05) after 150 min for the administration of 1 g/kg. However, treatment through a supplemented diet resulting in an average daily intake of 0.35 g/kg of CDP-choline for up to 60 days did not significantly alter homocysteine concentration. Old rats showed a significantly (P<0.05) lower homocysteine level (25%) than control young animals, even after 60 days of treatment with the supplemented diet. Thus, when rats are used in experimental studies on the beneficial effects of CDP-choline, it has to be considered that administration of high doses of CDP-choline will not affect the plasma levels of the risk factor homocysteine as long as the compound is not administered as a single bolus.     

Role of intrarenal alpha(2)-adrenoceptors in the renal responses to xylazine in rats

This study examined the contribution of intrarenal alpha(2)-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (U(Na)V) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the alpha(2)-adrenoceptor antagonist yohimbine (5 microg) significantly decreased V from 58 +/- 8 to 35 +/- 7 microl. min(-1). g kidney wt(-1) and U(Na)V from 2.8 +/- 0.4 to 2.1 +/- 0.4 microeq. min(-1). g kidney wt(-1) without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 microg) significantly reduced left and right kidney V, with no effects on U(Na)V. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 +/- 9 to 13 +/- 2 microl. min(-1). g kidney wt(-1 )and U(Na)V from 4.5 +/- 0.5 to 1.1 +/- 0.1 microeq. min(-1). g kidney wt(-1). In RDNX rats, this dose of yohimbine reduced V and U(Na)V, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and U(Na)V to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamine-anesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic alpha(2)-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.     

Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys

The use of indomethacin in preterm newborn infants with symptomatic patent ductus arteriosus is associated with compromised renal function. Ibuprofen has been shown to be as effective as indomethacin with fewer renal side effects. We examined the hypothesis that early postnatal ibuprofen has less adverse effects on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than indomethacin. Newborn rats received IP injections of human therapeutic doses of ibuprofen or indomethacin on the first 3 days of life. Control rats were treated with equivalent volume saline. Kidneys were assessed in suckling and weanling rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats, indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha), whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was sustained in weanling rats with indomethacin. Our findings demonstrate that indomethacin exhibits more potent suppressive effects on renal COX-2 and vasodilator prostanoids which are important regulators of renal development and function. These long-term, sustained effects may explain in part, why indomethacin exerts more severe adverse renal effects than ibuprofen, when administered during early postnatal life.     

Morphine inhibits TRH-induced intestinal transit increases

The current study examined the effects of intraperitoneal (IP) and intracisternal (IC) administration of the opiate agonist, morphine, and an opioid, central beta-endorphin, on thyrotropin releasing hormone (TRH)-induced small intestinal transit increases. Anesthetized rats, 14-day and older, were studied to determine age-related differences. Results showed that in all age groups IP morphine (2 mg/kg) blocked TRH (15 μg)-induced increases in transit of a charcoal bolus. Morphine 1 μg and beta-endorphin 1 μg administered IC in 0.6 μl failed to block TRH (10 μg)-induced increases in intestinal transit in 14-day-old rats. However, both morphine and beta-endorphin 1 μg IC blocked TRH-induced increases in adult rats. Dose-response studies demonstrated that higher doses (> 1 μg) of morphine IC were required to block TRH-induced increases in preweaning rats.     

甘西鼠尾草对大鼠高原肺动脉高压的干预作用及机制*

目的:探讨甘西鼠尾草(SPM)对大鼠高原肺动脉高压(HAPH)的干预作用及可能的机制。方法:将雄性SD大鼠随机分成对照组、缺氧组、SPM(0.5 g/kg、1 g/kg、2 g/kg)剂量组,每组14只,对照组饲养于西宁(海拔约2260 m),其余组均饲养于玛多县人民医院(海拔约4260 m)。SPM剂量组灌胃不同浓度的SPM(1 ml/100 g),浓度分别为0.5 g/kg、1 g/kg、2 g/kg,对照组和缺氧组灌胃等体积蒸馏水,每日一次,连续4周后,测定大鼠平均肺动脉压(mPAP)并取相同部位肺组织置液氮保存备用。采用RT-PCR法测定每组大鼠肺组织中的细胞增殖核抗原(PCNA)、细胞周期素依赖激酶(CDK4)、细胞周期蛋白D(CyclinD1)、RhoA(Ras同源基因家族成员A)、ROCK1、ROCK2的mRNA表达水平。结果:与对照组比较,缺氧组大鼠mPAP、肺组织中PCNA、CDK4、CyclinD1、RhoA、ROCK1、ROCK2的mRNA表达水平均明显升高(P＜0.01)。与缺氧组比较,SPM剂量组大鼠的mPAP、肺组织中PCNA、CDK4、CyclinD1、RhoA、ROCK1、ROCK2的mRNA表达水平均明显降低(P＜0.05或P＜0.01)。结论:SPM对大鼠HAPH具有一定的预防作用,其机制可能与抑制肺动脉平滑肌细胞过度增殖和RhoA/Rho激酶(ROCK)信号通路过度激活有关。