Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats.

Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.     

Effects of naltrexone on plasma corticosterone in opiate-naive rats: A central action

We have previously reported the elevation of plasma corticosterone by i.v. naloxone HC1 (NX). This work has been extended, with the current study, showing a similar effect with naltrexone HC1 (NTX) and that this effect is due to a central action of the drug. Using opiate-naive male rats with chronic i.v. catheters, stereotaxically placed intracerebroventricular (ICV) cannula guides where necessary, and sound-attenuated one-way vision boxes, serial blood samples were obtained from conscious unrestrained animals. NTX (5.0, 10.0 or 20.0 mg/kg i.v.) resulted in a significant increase in plasma corticosterone 15 min following injection. I.V. administration of the methylbromide salts of each drug, which do not cross the blood-brain barrier, did not produce this same elevation in hormone level at several doses (0.4, 1.0, 2.0, 10.0 or 20.0 mg/kg). In contrast, ICV injection of either of the quaternary salts (50 μg/10 μl/animal) resulted in an immediate and sustained rise in plasma corticosterone. Results obtained demonstrate that NTX has a similar effect on plasma corticosterone as NX at the appropriate doses and that the effect is a central rather than a peripheral one.     

Central histaminergic stimulation of pituitary--adrenocortical response in the rat

In conscious rats histamine, the H1-receptor agonist 2-pyridylethylamine (PEA), and the H2-receptor agonists dimaprit and impromidine given intracerebroventriculary (i.c.v.) increased the hypophyseal-adrenocortical response, evaluated indirectly through the corticosterone concentration in the blood serum. On a molar basis histamine was the most potent drug whereas its agonists were less potent in inducing an increased corticosterone response. Impromidine however, was far more active than dimaprit and PEA. The effect of histamine was significantly yet not totally antagonized by either mepyramine, a H1-receptor antagonist, or cimetidine, a H2-receptor blocker. The combination of mepyramine and cimetidine caused a considerably stronger inhibition than that induced by either antagonist given separately. Mepyramine impaired the corticosterone response to PEA, and the responses to impromidine and dimaprit were significantly diminished by cimetidine. The results suggest that i.c.v. histamine increases the pituitary-adrenocortical activity via both H1- and H2-receptors, and there seems to be no significant prevalence of either of these receptors in mediating this action of histamine.     

The effect of d-fenfluramine on anterior pituitary hormone release in the rat: in vivo and in vitro studies

Administration of d-fenfluramine, a serotonin-releasing drug, to male rats induced a dose-dependent increase in both serum prolactin and corticosterone concentrations. Serum growth hormone levels increased, but not significantly, at a dose of 1.25 mg/kg i.p. and decreased significantly at higher doses. When rats were pretreated with the serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) 30 min prior to injection of d-fenfluramine (5 mg/kg i.p.), the serum prolactin response to d-fenfluramine was partially inhibited, whereas the growth hormone response was not significantly modified. Fluoxetine pretreatment increased the serum corticosterone to the same level as did d-fenfluramine. d-Fenfluramine's effect on prolactin and growth hormone release was further tested in a hypothalamic-pituitary in vitro system. The addition of d-fenfluramine (5-500 ng/mL) for 30 min to rat hypothalami resulted in an enhancement of prolactin and growth hormone-releasing activities. These were expressed as the ability of the media in which the hypothalami had been incubated to stimulate prolactin and growth hormone release by cultured pituitary cells. The data suggest that the effect of d-fenfluramine on prolactin secretion is exerted through the hypothalamus and is probably mediated, at least partially, by a serotoninergic mechanism. The mechanism of d-fenfluramine's effect on corticosterone and growth hormone release needs further evaluation.     

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.     

Effect of constitutive- and inducible-cyclooxygenase in the carbachol-induced pituitary-adrenocortical response during social stress.

Acetylcholine potently stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Cholinergic receptor agonist carbachol, given intraperitoneally (i.p.) or into the lateral cerebral ventricle (i.c.v.) to non-anesthetized rats acts via multiple pathways to stimulate the HPA axis. The present study sought to determine 1) the functional selectivity of carbachol for cholinergic muscarinic and/or nicotinic receptors involved in the stimulation of HPA axis; 2) the involvement of prostaglandins (PGs) generated by constitutive and inducible cyclooxygenase (COX-1 and COX-2) in the carbachol-induced ACTH and corticosterone secretion in non-stressed rats and animals exposed to social crowding stress for 7 days (24 per a cage for 6). Carbachol was given i.c.v. or i.p. and cholinergic receptor antagonists or cyclooxygenase isoenzyme antagonists were given by the same routes 15 min earlier. One hour after the last injection trunk blood was taken for ACTH and corticosterone determinations. Atropine (0.1 microg i.c.v.), a cholinergic receptor antagonist, totally abolished the carbachol (2 microg i.c.v.)-induced ACTH and corticosterone secretion and mecamylamine (20 microg i.c.v.), a selective nicotinic receptor antagonist, did not affect this secretion. This finding indicates that carbachol functions as a selective central cholinergic muscarinic receptor agonist for the HPA axis stimulation. Crowding stress significantly diminished the carbachol (0.2 mg/kg i.p.)-induced plasma ACTH and corticosterone levels measured 1 hr after administration. Pretreatment with indomethacin (2 mg/kg i.p.), a non-selective cyclooxygenase inhibitor, significantly diminished the ACTH and corticosterone responses to carbachol (0.2 mg/kg i.p.) in control rats and moderately decreased these responses in stressed rats. Piroxicam (0.2 and 2.0 mg/kg i.p.), a COX-1 inhibitor, considerably impaired the carbachol-induced ACTH and corticosterone responses in control rats and markedly diminished these responses in stressed rats. A selective COX-2 blocker, compound NS-398 (0.2 and 2.0 mg/kg i.p.), substantially decreased the carbachol-induced hormones secretion in control rats but did not markedly alter this secretion in stressed rats. These results indicate that in the carbachol-induced HPA axis activation PGs generated by COX-1 are considerably and to a much greater extent involved than PGs generated by COX-2. Social stress markedly diminishes the mediation of PGs generated by COX-1 but PGs synthesized by COX-2 do not substantially participate in the carbachol-induced HPA response.     

MDL-646, a new synthetic E1-prostaglandin with local protective effects on the gastric mucosa

The gastric protection, diarrheogenic and arterial hypotensive effects of MDL-646, a PGE1 derivative, have been studied in rats. The compound administered p.o. or i.v. was able to inhibit the macroscopic damage to gastric mucosa produced by noxious stimuli (ethanol and indomethacin). In the stomach perfusion test with the anesthetized rat, intravenously administered MDL-646 reduced histamine- or pentagastrin-stimulated gastric secretion. After intraduodenal administration (i.d.) doses at least 40-50 times greater were necessary for an antisecretory effect. In conscious rats with chronic gastric fistulas, intragastrically administered (i.g.) MDL-646 affected both acid concentration and volume of unstimulated gastric secretion. In experimental models for gastric lesions, MDL-646 was much more potent after oral (p.o.) (15-30 times) than after i.v. administration. (ED50 micrograms/kg: vs. alcohol lesions, 0.05 p.o. and 0.7 i.v.; vs. indomethacin ulcers, 7.0 p.o. and 195 i.v.). Our data would fit the hypothesis that it was a local effect on the gastric mucosa. The mechanism of this effect is not known. The supposed local activity coupled with the antisecretory effects and the good tolerability make it interesting to test MDL-646 as an anti-ulcer agent in man.     

Enhanced serum glucocorticoid levels mediate the reduction of serosal mast cell numbers in diabetic rats.

Rats turned diabetic by treatment with alloxan exhibit a significant reduction in serosal mast cell numbersin parallel with decreased insulin levels in the plasma. Our aim was to investigate the putative involvement of endogenous glucocorticoid hormone in this phenomenon. The findings indicated that rats treated with alloxan responded with an increase in levels of serum corticosterone concomitantly with decreased mast cell numbers in the pleural space. We found that either surgical bilateral adrenalectomy or pretreatment with the steroid antagonist RU 486 (20 mg/kg, i.p.) impaired the drop in pleural mast cell counts in alloxinated rats. Administration of insulin (15 U/kg) prevented the increase in corticosterone levels and restored pleural mast cell levels in diabetic animals. In addition, treatment of naive rats with corticosterone (0.5 mg/kg, s.c.) or dexamethasone (0.1 mg/kg, s.c.), for 3 consecutive days, led to a reduction in the number of mast cells recovered from the pleural cavity as noted in diabetic animals. In contrast, insulin reduced serum corticosterone levels and induced a significant elevation in pleural mast cell numbers in naive rats. We conclude that there is a causative relationship between increased levels of glucocorticoids and down-regulation of mast cell numbers associated with the diabetic state, both phenomena clearly sensitive to insulin.     

MDL-646, a new synthetic E1-prostaglandin with local protective effects on the gastric mucosa

The gastric protection, diarrheogenic and arterial hypotensive effects of MDL-646, a PGE₁ derivative, have been studied in rats. The compound administered p.o. or i.v. was able to inhibit the maroscopic damage to gastric mucosa produced by noxious stimuli (ethanol and indomethacin). In the stomach perfusion test with the anesthetized rat, intravenously administered MDL-646 reduced histamine- or pentagastrin-stimulated gastric secretion. After intraduodenal administration (i.d.) doses at least 40–50 times greater were necessary for an antisecretory effect. In conscious rats with chronic gastric fistulas, intragastrically administered (i.g.) MDL-646 affected both acid concentration and volume of unstimulated gastric secretion. In experimental models for gastric lesions, DML-646 was much more potent after oral (p.o.) (15–30 times) than after i.v. administration. (ED₅₀ μg/kg: vs. alcohol lesions, 0.05 p.o. and 0.7 i.v.; vs. indomethacin ulcers, 7.0 p.o. and 195 i.v.). Our data would fit the hypothesis that it was a local effect on the gastric mucosa. The mechanism of this effect is not known. The supposed local activity coupled with the antisecretory effects and the good tolerability make it interesting to test MDL-646 as an anti-ulcer agent in man.     

Effect of subdiaphragmatic vagotomy and cholinergic agents in the hypothalamic-pituitary-adrenal axis activity.

In the present study, we examined whether the vagus nerve is involved in mediating the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic and nicotinic agonists, carbachol and nicotine. The site of HPA axis muscarinic stimulation was determined using peripheral (i.p.) and intracerebroventricular (i.c.v.) administration of carbachol, atropine sulphate (AtrS) and atropine hydrobromide (AtrBr). The i.p. carbachol-(0.5 mg/kg)-induced corticosterone response was significantly reduced by i.p. pretreatment with AtrBr (0.1 mg/kg), but was not diminished by i.c.v. AtrS (0.1 mug). The increase in corticosterone secretion induced by i.c.v. carbachol (2 microg) was totally abolished by i.c.v. pretreatment with AtrS (0.1 microg) but was not altered by i.p. AtrBr. Subdiaphragmatic vagotomy performed 2 weeks earlier substantially decreased the i.p. carbachol (0.2 mg/kg)-induced ACTH response and markedly augmented ACTH and corticosterone response to a higher dose of carbachol (0.5 mg/kg) in comparison with the responses in sham operated rats. Vagotomy abolished the stimulatory effect of i.p. nicotine in a low dose (1 mg/kg) on ACTH and corticosterone secretion; the ACTH response to higher dose (2.5 mg/kg) was considerably reduced, while corticosterone response remained unaffected. These results suggest that carbachol given i.c.v. evokes considerable corticosterone response by stimulation of central cholinergic muscarinic receptors. A major part of the i.p. carbachol-induced corticosterone secretion results from peripheral cholinergic muscarinic receptor stimulation. Subdiaphragmatic vagotomy moderately intensified the carbachol-induced ACTH and corticosterone secretion. Vagotomy significantly reduced the nicotine-induced ACTH secretion, possibly by the involvement of vagal afferents. The nicotine-induced corticosterone secretion is not exclusively regulated by circulating ACTH but by various intra-adrenal regulatory components.     

Effects of naloxone on plasma corticosterone in the opiate-naive rat

Naloxone HCl (NX) has long been considered to be a pure narcotic antagonist, having an effect only subsequent to pretreatment with a narcotic. Characteristically, low doses of NX have been used to antagonize the effects of analgesic doses of narcotics and to precipitate withdrawal in chronically treated animals. In this study, the effects of high doses of NX (2.0–20.0 mg/kg) on changes in plasma corticosterone were examined in the opiate-naive animal. Using male rats with chronic intravenous catheters and one-way vision boxes, injections were made and serial blood samples were obtained in the conscious, unrestrained animal. The acute administration of NX to the opiate-naive animal produced a dose-related increase in plasma corticosterone with respect to both amplitude and duration. NX (10.0 mg/kg i.v.) produced a significant elevation in hormone level at 15 and 30 minutes. With NX (20.0 mg/kg i.v.) the duration of the response was extended to 60 minutes. To examine whether short-term tolerance to this effect could be produced, animals were given a single pretreatment with either NX (10.0 mg/kg) or saline i.v. Two hours later NX produced a similar elevation in hormone level in both groups. The effect of chronic injection of NX was also studied. Animals pretreated with either NX (10.0 mg/kg) or saline s.c. once daily for 7 days did not show a significant difference following the subsequent administration of NX. In both cases, a significant elevation of plasma corticosterone resulted. The results suggest that NX may have a direct effect on opiate receptors resulting in an elevation of plasma hormone levels or NX may be disrupting an endogenous opiate-receptor interaction producing a stress response.     

Adrenocortical stimulation by a cholecystokinin preparation in the rat

The effect of a cholecystokinin (CCK) preparation on the secretion of corticosterone when injected intraperitoneally and intraventricularly was studied in the rat. Both routes of injections produced pronounced elevation of plasma corticosterone levels, but the minimum effective dose by intraventricular injection was 10 mU/rat and that by intraperitoneal injection 2 U/100 g, or approximately 5 U/rat. Although the effect was observed in vagotomized rats, CCK did not affect the pituitary gland itself. It was inferred that CCK acts directly or indirectly on CRF neurones in the brain. Since CCK preparation used in the present experiments was contaminated with motilin, the effect of synthetic motilin on the adrenocortical secretion was also examined. However, no stimulatory effect was found following intraventricular injection of this peptide.     

Brain histamine-plasma corticosterone interactions

Significant elevation in plasma corticosterone of rats achieved by intraperitoneal (i.p.) administration of corticosterone (2.4 mg/kg) was associated with a rapid (2.5 min) and significant increase in hypothalamic histamine (HA) levels which persisted for 60 min. Midbrain and cortical HA concentrations were not affected. Significant and prolonged elevation of hypothalamic, midbrain and cortical HA levels was achieved by L-histidine administration (500 mg/kg i.p.). The most significant increase was noted in the hypothalamus and persisted for 10 hours. The elevated brain HA levels were associated with significant increase in plasma corticosterone levels which lasted for 120 mins. Present data supports the involvement of central HA in endocrine function.     

Role of noradrenergic neurons in ethanol-induced elevation of free fatty acids and corticosterone

The effects of ethanol (2 or 3 g/kg) on plasma corticosterone and free fatty acids were examined in rats with bilateral electrolytic lesions of locus coeruleus or pretreated with the noradrenergic neurotoxin DSP 4 (50 mg/kg). Both lesions and DSP 4 significantly attenuated ethanol induced elevation of free fatty acids. No changes in basal levels of free fatty acids or corticosterone were observed nor did either treatment alter the elevating effect of ethanol on corticosterone. The results indicate that ethanol alters plasma free fatty acids through mechanisms involving noradrenergic neurons in the central nervous system.     

Effects of caffeine and bombesin on ethanol and food intake

The methylxanthine caffeine and ethyl alcohol are widely used and powerful psychotropic drugs, but their interactions are not well understood. Bombesin is a brain-gut neuropeptide which is thought to function as a neurochemical factor in the inhibitory control of voluntary alcohol ingestion. We assessed the effects of combinations of intraperitoneal (i.p.) doses of caffeine (CAF, 0.1-50 mg/kg) and bombesin (BBS, 1-10 micrograms/kg) on 5% w/v ethanol solution and food intake in deprived rats. Deprived male and female Wistar rats received access to 5% ethanol or Purina chow for 30 minutes after i.p. injections. In single doses, CAF and BBS significantly decreased both ethanol and food consumption, at 50 mg/kg and 10 micrograms/kg, respectively. CAF and BBS combinations produced infra-additive, or less-than-expected inhibitory effects on ethanol intake, but simple additive inhibitory effects on food intake. This experimental evidence suggests a reciprocal blocking of effects of CAF and BBS on ethanol intake but not food intake. Caffeine, when interacting with bombesin, increases alcohol consumption beyond expected values. Caffeine could affect the operation of endogenous satiety signals for alcohol consumption.     

The effect of amperozide, a new antipsychotic drug, on plasma corticosterone concentration in the rat.

Amperozide is an atypical antipsychotic drug with high affinity for the serotonin 5-HT2 receptor but with low affinity for the dopamine D1 and D2 receptors. Amperozide dose-dependently increased the level of plasma corticocorticosterone in the rat. The effect of amperozide on plasma corticosterone was not inhibited by pretreatment with the 5-HT1A receptor antagonist pindolol or the 5-HT2 receptor antagonist ritanserin. Nor was it inhibited by the dopamine D2 receptor antagonist haloperidol. In contrast to ritanserin, amperozide did not antagonize plasma corticosterone elevation elicited by the serotonin receptor agonist MK-212. Similar to the serotonin uptake inhibitor fluoxetine, amperozide (0.5 mg/kg) significantly (p < 0.05) blocked p-chloroamphetamine (PCA) induced corticosterone release 4 and 16 hrs after amperozide administration. However, amperozide significantly increased the plasma corticosterone concentration also in rats pretreated with parachlorophenylalanine (PCPA). These data suggest that other mechanisms than a 5-HT uptake inhibitory effect are involved in the acute stimulation of corticosterone by amperozide.     

Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation

The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.     

Atrial natriuretic factor is unlikely to be involved in the reduced aldosterone production in the Brattleboro rat

We have previously reported that basal and stimulated aldosterone production in Brattleboro rat (DI) lacking hypothalamic arginine vasopressin is lower than that observed in control Long-Evans rat (LE). In the present study, we investigated the secretion under various experimental conditions, adrenal binding sites, and the aldosterone-inhibiting effect of atrial natriuretic factor (ANF). In the conscious resting state, the plasma ANF concentration was similar between LE and DI rats. Pentobarbital anaesthesia (5 mg/100 g body wt.) reduced the plasma ANF concentration equally in both groups, with or without captopril pretreatment. Morphine (10 mg/100 g body wt.) increased ANF secretion dramatically and equally in the two groups of pentobarbital anaesthetized (2 mg/100 g body wt.) rats. In dexamethasone pretreated-pentobarbital anaesthetized rats, a concurrent i.v. ANF infusion (50 ng/min) did not change significantly the corticosterone response to ACTH (1-24) (1 mI.U./100 g body wt.) but steeply depressed ACTH-induced aldosterone production to a similar extent between DI and LE rats. A single class of adrenal ANF receptor sites was found with a similarity in high affinity and maximum binding capacity between the two groups of rats. Taken together, these results suggest that the reduced aldosterone production by Brattleboro rat adrenals is unlikely to be related to the inhibitory effect of ANF.     

Carbaryl-induced elevation of corticosterone level and cholinergic mechanism

Administration of a single dose (200 mg/kg, p.o.) of carbaryl to rats produced a significant rise in adrenal and plasma corticosterone levels and an increase of tyrosine alpha-ketoglutarate transaminase activity in the liver cytosol. Synaptosomal acetylcholinesterase activity of the hypothalamic and the striatal regions of rat brain was decreased by carbaryl treatment under similar conditions. Pretreatment (0.5 h) with atropine sulphate (10 mg/kg, i.p.) failed to counteract the carbaryl-induced elevation of adrenal and plasma corticosterone levels and hence the liver tyrosine alpha-ketoglutarate transaminase activity. Present results suggest that the carbaryl-induced rise in the corticosterone level in the adrenal gland and plasma is not due to a cholinergic mechanism.     

CCK-8对内毒素休克大鼠肺脏细胞因子的抑制效应

观察八肽胆囊收缩素(cholecystokinin-octapeptide,CCK-8）改善脂多糖(lipopolysaccharide,LPS）引起的大鼠内毒素性休克（endotoxic shock,ES）过程中血清及肺脏细胞因子的变化,探讨p38比裂素活化蛋白激酶（p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入LPS(p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入 LPS（8mg/kg i.v.）复制的SD大鼠ES模型、LPS注入前10min尾静脉注入CCK-8(40ug/kg i.v.）、单独注入CCK-8(40Uug/kg i.v.）或生理盐水（对照）的四组大鼠平均动脉血压（MAP）的改变,应用ELISA试剂盒检测血清和肺脏中炎性细胞因子（TNF-a、IL-1β和IL-6）的变化。用Western blot检测肺脏p38 MAPK的表达。结果显示：CCK-8可改善LPS引起的大鼠MAP的下降。与对照组相比,LPS可显著增加血清和肺脏TNF-a、IL-1β和IL-6含量;CCK-8可显著抑制LPS诱导的血清和肺脏TNF-a、IL-1β和IL-6的增加。CCK-8可增加ES大鼠肺脏磷酸化p38 MAPK的表达。结果提示CCK-8可改善ES大鼠MAP的降低,并对肺脏促炎性细胞因子过量产生有抑制作用,p38MAPK可能参与了其信号转导机制。