| All physiologic activities of human being are dependent on outside environment conditions. Dynorphin A is one type of endogenous peptide and plays an important role in the activities of neuroendocrine system and cardiovascular modulation. Dyoirphin A level in our body keeps in dynamic balance when outside environment is stable. While the environment conditions changed, the balance of dynophin A level will be destroyed by stress. Dynorphin A is considered as one type of neuromodulator or neurotransmitter and there are great amounts of dynrophin A and its mRNA distribution in central neural system. Dynrophin A can exert effects on the activity of other neuropeptides such as CRF, ACTH and vasopressin. Dynorphin A has abroad biological effects and has been found to play important roles in several activities of central neural system. Hypothalamus is the endogenous center of animal, as well as the stress-reactivity center. It is valuable in clinical application and theory research to have a further study in the relationship between dynorphin A and hypothalamus.Hypoxia is one type of special stress. It can induce providing deficience of oxygen in animal bodies, then affect the biological activity of neuroendogenous system. The expression of dynorphin A will be altered under hypoxia. So, we will discuss the effect of hypoxia on dynorphin A expression and the possible modulating mechanism undergoing.We study the expression alteration of rat hypothalamic dynorphin A under 2km and 5km hypoxia by applying simulated altiplano hypoxia. We also applied simulated combined stress to study the effect of 2km intermittent hypoxia, 4℃ cold, restraint and their combination on rat hypothalamic dynorphin A. the technique we used to determine rat hypothalamic dynorphin A and its mRNA level is immunohistochemistry and in situ hybrization. We study the modulating mechanism of dynorphin A during hypoxia by injection CRF-R1 into rat. Results: 1) Effect of 2km and 5km continual (1, 2, 5, 10, 15 and 25 day) hypoxia ondynorphin A peptides level in rat paraventricular nucleus, supraoptic nucleus andmedian eminence.In rat paraventricular nucleus, dynorphin A level increased on 10th, 15th and 25th day under 2km continual hypoxia and increased on 15th and 25* day under 5km continual hypoxia.In rat rupraoptic nucleus, dynorphin A level increased on 5th, 10th. 15th and 25th day under 2km continual hypoxia, and increased on 2nd,5th,10lh,15th and 25th day under 5km continual hypoxia.In rat mecian eminence, immunostaining dynorphin A level was elevated in the first two day , then decreased on 10th, 15th and 25th day under both 2km and 5km continual hypoxia.2) Effect of intermittent 2km hypoxia and its combined stress with cold and restraint on rat paraventricular nucleus dynorphin A level.Immunostaining dynorphin A level in rat paraventricular nucleus increased under 4°Ccold, 4°Ccold+2km hypoxia and restrain conditions. Dynorphin A level increased obviously under restraint compared with the level under 2km intermittent hypoxia + restraint in rat paraventricular nucleus.3) Under 5km continual hypoxia for 5 day, dynorphin A peptides level increased a little in rat paraventricular nucleus and decreased a little in rat median eminence. After CP154,526 injection, dynorphin A peptides level decreased to control level in rat paraventricular nucleus and increased to control level in rat meidan eminence compared with CP 154,526 injected groups. But in all groups metioned above, there is no marked difference between each other.Otherwise, after in situ mRNA hybridization histochemistry, it showed, prodynorphin mRNA in the paraventricular increased a little (not marked) under 5km continual hypoxia for 5 day, and decreased obviously in CP 154.526 injection group compared with the hypoxia group.Our results indicate that: (1) hypoxia could stimulate the expressions of PVN and SON dynorphin A, and stimulate the expressions of ME dynorphin A in shorttime ,suppress the expressions of ME dynorphin A in long time. (2) restraint stress and cold stress had more obvious effect on PVN dynorphin A expression than intermittent 2km hypoxia; combinative stress had less influence on PVN dynorphign A level compared with single stress. (3) CRF probably plays an important role in modulating the PVN dynorphin A expression under chronic continual hypoxia condition.
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