Effect of gamma-hydroxybutyric acid receptor on focal cerebral ischemia-reperfusion injury in rats.
- Author:
Rong JIN
1
;
Xin-Ying JIANG
;
Xing MA
;
Shu-Ling GU
;
Ti-Jun DAI
Author Information
1. Department of Pharmacology, Xuzhou Medical College, Xuzhou 221002, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Benzocycloheptenes;
pharmacology;
Calcium;
metabolism;
Cerebral Cortex;
metabolism;
Cerebral Infarction;
pathology;
Cyclic GMP;
metabolism;
Infarction, Middle Cerebral Artery;
complications;
Male;
Neuroprotective Agents;
pharmacology;
Nitric Oxide;
metabolism;
Nitric Oxide Synthase;
metabolism;
Nitric Oxide Synthase Type II;
metabolism;
Random Allocation;
Rats;
Rats, Sprague-Dawley;
Receptors, Cell Surface;
agonists;
antagonists & inhibitors;
metabolism;
Reperfusion Injury;
etiology;
metabolism;
pathology
- From:
Acta Pharmaceutica Sinica
2007;42(8):838-842
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the effect of gamma-hydroxybutyric acid receptor (GHBR) on focal cerebral ischemia-reperfusion injury in rats and its mechanism. NCS-356 (the agonist of GHBR) and NCS-382 (the antagonist of GHBR) were adopted as the tool medicine. The ripe male Sprague-Dawley rats weighing 240 - 280 g were randomly divided into seven groups: sham operation group (sham), ischemia-reperfusion group (Isc/R), NCS-356 160 microg x kg(-1) group (N1), NCS-356 320 microg x kg(-1) group (N2), NCS-356 640 microg x kg(-1) group (N3), NCS-382 640 microg x kg(-1) + NCS-356 640 microg x kg(-1) group (NCS-382 + N3), and nimodipine (Nim) 600 microg x kg(-1) group. The middle cerebral artery occlusion (MCAO) model referring to Longa's method with modifications was adopted. The effect of GHBR on behavioral consequence of MCAO rats was studied after 2 h of ischemia-reperfusion. After 24 h of ischemia-reperfusion, part of animals were used to measure the cerebral infarction volume by TTC staining; ischemic cortex of another part of animals were used to measure the content of intracellular free calcium by flow cytometry, the tNOS, iNOS activity and the content of NO by spectrophotometric method, the content of cGMP by radioimmunoassay. The neurological function score and infarction volume rate in Isc/R group rats increased significantly than that in sham group; The content of intracellular calcium ([Ca2+]) of cortex neuron and cGMP, the activities of tNOS and iNOS, and the content of NO in Isc/R group were higher than that in sham group obviously (P < 0.01); These consequence we mentioned of N1, N2, N3 and Nim group were lower than that of Isc/R. NCS-382 + N3 group could significantly antagonize the above effect of N3. Thus, NCS-356 has protective effects against ischemia-reperfusion brain injury by activating GHBR. The neuroprotective effect of GHBR is related with decreasing the content of [Ca2+]i, NO, cGMP and tNOS, iNOS activity in MCAO rats.
