Combined administration of anisodamine and neostigmine produces anti-shock effects： involvement of a7 nicotinic acetylcholine receptors  

作　　者：Li SUN Gu-fang ZHANG Xin ZHANG Qing LIU Jian-guo LIU Ding-feng SU Chong LIU 

机构地区：[1]Department of Pharmacology,Second Military Medical University,Shanghai 200433,China

出　　处：《Acta Pharmacologica Sinica》2012年第6期761-766,共6页中国药理学报（英文版）

摘　　要：Aim： To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. Methods： Kunming mice were injected with lipopolysaccharide （LPS 30 mg/kg, ip） to induce endotoxic shock. Anisodamine （12.5, 25, and 50 mg/kg, ip） and neostigmine （12.5, 25, and 50 μg/kg, ip） were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-a and IL-113 were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in a7 nicotinic acetylcholine receptor （a7 nAChR） knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. Results： In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti- shock effect of combined anisodamine and neostigmine was abolished in （x7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective a7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. Conclusion： The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of a7 nAChRs.Aim： To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. Methods： Kunming mice were injected with lipopolysaccharide （LPS 30 mg/kg, ip） to induce endotoxic shock. Anisodamine （12.5, 25, and 50 mg/kg, ip） and neostigmine （12.5, 25, and 50 μg/kg, ip） were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-a and IL-113 were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in a7 nicotinic acetylcholine receptor （a7 nAChR） knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. Results： In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti- shock effect of combined anisodamine and neostigmine was abolished in （x7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective a7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. Conclusion： The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of a7 nAChRs.

关 键 词：ANISODAMINE NEOSTIGMINE PNU282987 a7 nicotinic acetylcholine receptor endotoxic shock hemorrhagic shock 

分 类 号：S852.32[农业科学—基础兽医学] TQ460.34[农业科学—兽医学]