胆碱能抗炎通路对失血性休克大鼠保护作用的研究
李建国 胡正芳 杜朝晖 周青 贾宝辉 彭周荃 叶小丰 李蓓【摘要】 目的 探讨胆碱能抗炎通路的抗休克作用及其可能的机制。方法 采用改良Wiggers法复制失血性休克动物模型。30只成年雄性SD大鼠随机分为假失血组(假Hem组)、失血性休克组(Hem组)、迷走神经切断组(VGX组)、迷走神经电刺激组(STM组)、胆碱酯酶抑制组(THA组)和N受体拮抗组(α-BGT组)。将左迷走神经远端连接刺激电极，于制模成功后即刻行电刺激(5 V、2 ms、1 Hz)12 min。颈总动脉置管连续监测平均动脉压(MAP)，模型稳定后45 min测定各组动物血浆肿瘤坏死因子-α(TNF-α)和肝组织核因子-κB(NF-κB)含量。结果 失血性休克动物的MAP持续处于低水平状态。与假Hem组比较，Hem组血浆TNF-α含量明显升高(P<0.01)，肝组织NF-κB表达明显增强。迷走神经电刺激组动物MAP迅速升高，血浆TNF-α含量较Hem组显著降低(P均<0.01)，肝组织NF-κB表达减弱。迷走神经离断后静脉注射胆碱酯酶抑制剂四氢氨基丫啶(THA)可产生与电刺激迷走神经类似的作用，但电刺激前静脉注射N胆碱能受体α7亚单位阻断剂(α-BGT)，则可消除电刺激迷走神经的抗休克效应。结论胆碱能抗炎通路具有潜在的抗失血性休克作用，其机制可能是通过抑制休克病程中过度的全身性炎性反应而实现的。
【关键词】 休克，失血性； 迷走神经; 电刺激; 乙酰胆碱； 肿瘤坏死因子-α; 核因子-κB
Protective effect of the cholinergic anti-inflammatory pathway against hemorrhagic shock in rats
LI Jian-guo, HU Zheng-fang, DU Zhao-hui, ZHOU Qing, JIA Bao-hui, PENG Zhou-quan, YE Xiao-feng, LI Bei.
Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, China
【Abstract】Objective To investigate the effect of the cholinergic anti-inflammatory pathway on hemodynamics in hemorrhaged rats. Methods Hemorrhagic shock was induced by modified Wiggers method until mean arterial pressure (MAP) was stabilized within the range of 35 to 40 mm Hg (1 mm Hg=0.133 kPa). Thirty male Sprague-Dawley rats were randomly divided into six groups: sham group, hemorrhagic shock(Hem) group, vagotomy (VGX) group, vagus stimulation(STM) group, cholinergic inhibitor (THA) group and N receptor inhibitor (α-BGT) group. The distal end of the left vagus nerve trunk was placed on bipolar platinum electrode connected to a stimulation module and controlled by an acquisition system. Stimuli with constant voltage (5 V, 2 ms, 1 Hz) were applied to nerve for 12 minutes, starting 5 minutes after MAP stabilized at a level of 35 to 40 mm Hg. Before stimulation a blood pressure transducer was implanted in the common carotid artery for continuous registration of MAP. Blood samples and liver samples were collected from animals of all groups after stimulation. Serum levels of tumor necrosis factor-α(TNF-α) and liver nuclear factor kappa-B (NF-κB) were determined. Results MAP was markedly lowered at the end of bleeding, and the levels of serum TNF-α and liver NF-κB markedly increased 45 minutes after the bleeding was discontinued. Bilateral cervical vagotomy did not significantly modify the changes in serum TNF-α, but slightly increased liver NF-κB activation. Application of constant electric current to the distal end of the vagus trunk significantly reduced serum TNF-α and blunted liver NF-κB activation. Tetrahydroamino-acridine(THA,1.5 mg/kg, intravenous drip administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNF-α and liver NF-κB amounts, but α-bungarotoxin(1.0 μg/kg intravenous drip) pretreatment reverted the inhibitory effects of vagal stimulation. Conclusion The results suggest that direct electrial stimulation of the vagus nerve and its transmitter can significantly attenuate peak serum TNF-α amounts, inhibit the expression of liver NF-κB, and prevent the development of hypotension, thus it might produce a potential protective effect on hemorrhaged rats through acetylcholine(Ach) binds N Ach receptor α7 subunit which exists in the macrophage. ......
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