Effect of cholinergic anti-inflammatory pathway on cerebral ischemia-reperfusion injury in the rat

doi:10.3969/j.issn.1006-7795.2017.03.003

Abstract

Abstract: 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 Twenty-five male healthy Sprague-Dawley 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. 15 min before ischemia-reperfusion, we administered intracerebroventricularly (i.c.v.) Methoctramine(500 ng/kg,10 μL), McN-A-343(500 ng/kg,10 μL) and Choline(500 ng/kg,10 μL) 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 6 h in all groups. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels of 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-α and IL-1βcontent in hippocampus, heart, liver, kidney and plasma after ischemia.Choline could also attenuated TNF-α and IL-1βexpression in hippocampus but could not inhibit them in heart, liver, kidney and serum. TNF-α and IL-1β levels in lung could not be suppressed by methoctramine, McN-A-343 or choline. Compared with I/R, 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. The mechanisms of anti-inflammatory were likely to suppress the expression of TNF-α and IL-1β.

Key words: cholinergic anti-inflammatory pathway, vagus nerve, cerebal ischemia-reperfusion, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), methoctramine, McN-A-343, choline

CLC Number:

R743.31

Wang Xiao, Su Yue, Li Tianzuo, Zhao Binjiang. Effect of cholinergic anti-inflammatory pathway on cerebral ischemia-reperfusion injury in the rat[J]. Journal of Capital Medical University, 2017, 38(3): 342-347.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2017.03.003

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2017/V38/I3/342

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