| Objective To investigate the protective effect of cholinergic anti-inflammatory pathway (CAP) via the M1 receptor agonist,the M2 receptor antagonist and the nAChR7 agonist during cerebral ischemia-reperfusion injury in rats.Methods 25 male healthy Sprague-Daewley rats were randomly divided into five equal groups: sham operation (SHAM) group, ischemia reperfusion (I/R) group, Methoctramine (MET) group, McN-A-343(MA343) group and Choline(CHO) group. Rats were subjected to four-vessel occlusion (4-VO) global cerebral ischemia by electrocauterization of the bilateral vertebral arteries, except SHAM group.15min before ischemia-reperfusion, we administered intracerebroventricularly (i.c.v.) Methoctramine(500ng/kg,10μl),McN-A-343(500ng/kg,10μl)and Choline(500ng/kg,10μl) to MET group, MA343 group and CHO group, other groups receiving saline (0.9%). Then forebrain ischemia was induced by tightening of the clasps that around the common carotid arteries for 20 minutes, except SHAM group.Blood and tissue samples were collected after reperfusion for 6h in all groups. The levels of TNF-αand IL-1βin hippocampus, heart, liver, lung, kidney and plasma were measured by radio-immunoassay(RIA).Apoptosis was detected by terminal deoxynucleotidyl-trallsferase meiated dUTP nick end labeling(TUNEL).Results Methoctramine and McN-A-343 could markedly inhibit the increase of TNF-αand IL-1βcontent in hippocampus, heart, liver, kidney and plasma after ischemia .Choline could also attenuated TNF-αand IL-1βexpression in hippocampus but could not inhibit them in heart, liver, kidney and serum. TNF-αand IL-1βlevels in lung could not be suppressed by Methoctramine , McN-A-343 or Choline. Compared with I/R group, the apoptotic cells in MET group, MA343 group and CHO group were significantly decreased.Conclusion It is indicated that CAP plays a potential role in alleviating local and systemic inflammatory response during cerebral ischemia-reperfusion injury, and it also can inhibit the effect of apoptosis inderectly. The mechanisms of anti-inflammatory were likely to suppress the expression of TNF-αand IL-1β. |
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