Effects Of The Goat Combined Anaesthetic On NO Signal Transduction Pathway In Cental Nervous System In Goats

Objective: Many disadvantage factors were emerged during clinical anesthesia process because of the physiology feature of ruminant. At present, simple combined anesthesia could not satisfy the clinic request and the utility way to solve this problem must be compatibility drugs of different anaesthetic mechanism. The impacts of combined anaesthetic and its key components on signal transduction system in goats were researched to approach the molecule mechanism of anaesthetic, and to authenticate the rationality and scientific of the anaesthetic composition, providing data and rationale basic for compatibility anaesthetic reasonably and efficiently in clinical anesthesia.Method: Goats were divided into 4 groups randomly: control group which intramuscular injected by normal sodium; xylazine group which intramuscular injected by xylazine(12.8mg/kg) and midazolam group which intramuscular injected by midazolam(14mg/kg); and composition group which intramuscular injected by composition(1.31mL/kg).The changes of ethology were observed and the brain tissues were took in different anaesthetic periods. The activity of ATPase, NOS and the content of NO were determined by absorption spectrometry and the concentration of cGMP and cAMP were determined by ELISA.Results:1. The activities of Na⁺-K⁺-ATPase in cerebrum and thalamus of goats were obviously decreased at anesthetic stage in xylazine group. The activities of Na⁺-K⁺-ATPase in cerebrum, hippocamp, thalamus and brainstem were obviously decreased at anesthetic stage in composition group. These change tendencies above were consistent with the ethology changes in goats.2.The activities of Ca²⁺-Mg²⁺-ATPase in cerebrum, thalamus, cerebellum and brainstem were obviously decreased at anesthetic stage in xylazine, midazolam and composition groups. The activities of Ca²⁺-Mg²⁺-ATPase in hippocamp was obviously decreased at anesthetic stage in xylazine and composition groups, and these indexes above were increased at convalescence stage. These change tendencies above were consistent with the ethology changes in goats.3.The concentrations of cAMP in cerebrum, hippocamp, cerebellum and brainstem were obviously raised at anesthetic stage in xylazine, midazolam and composition groups. The concentration of cAMP in thalamus was obviously raised at anesthetic stage in xylazine and midazolam groups, and these indexes above were restored to normal level at convalescence stage. These change tendencies above were consistent with the ethology changes in goats.4.The activities of NOS, the contents of NO and cGMP in cerebrum, hippocamp, thalamus, cerebellum and brainstem were obviously decreased at anesthetic stage in xylazine, midazolam and composition groups, and they were restored to normal level at convalescence stage . These change tendencies of the indexes above were consistent with the ethology changes in goats.Conclusion:1.Na⁺-K⁺-ATPase in cerebrum and thalamus one of effect target sites of xylazine; Na⁺-K⁺-ATPase in cerebrum, hippocamp, thalamus and brainstem one of effect target sites of the combined anesthetic. The mechanism relate with depressing the activity of Na⁺,K⁺-ATPase.2.Ca²⁺-Mg²⁺-ATPase in cerebrum, thalamus, cerebellum and brainstem one of effect target sites of midazolam; Ca²⁺-Mg²⁺-ATPase in cerebrum, hippocamp, thalamus, cerebellum and brainstem one of effect target sites of xylazine and the combined anesthetic. The mechanism relate with depressing the activity of Ca²⁺-Mg²⁺-ATPase.3.The general anesthesia effect of xylazine and midazolam correlate with the signal transduction system of cAMP which was activated in cerebrum, hippocamp, thalamus, cerebellum and brainstem in goats. The signal transduction system of cAMP in cerebrum, hippocamp, cerebellum and brainstem participate in the regulation of mechanism in general anesthesia of the combined anesthetic.4.There are some dependablity between the effect of general anesthesia of xylazine, midazolam and the combined anesthetic and inhibited the signal transduction system of NO/cGMP in the encephalic regions discussed above.5. The inhibitory effects of the combined in activity of Na⁺,K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase and signal transduction system of NO/cGMP was stronger than xylazine and midazolam, and the activation effect of combined in signal transduction system of cAMP was weaker than xylazine and midazolam.