广藿香醇对精神应激型腹泻为主型肠易激综合征的抑制作用。

AIM: To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 × 10 mol/L to 1 × 10 mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1 × 10 mol/L to 1 × 10 mol/L); (2) neurotransmitter antagonists including N-nitro-L-arginine methyl ester hydrochloride (10 μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5'-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined. RESULTS: PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 ± 3.34) was significantly decreased in the peak tension ( < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC = 0.94 μmol/L) was significantly decreased by PA (EC = 37.43 μmol/L) ( < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 μmol/L) contraction ( < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats. CONCLUSION: PA application may serve as a new therapeutic approach for IBS-D.

目的：阐明广藿香醇（PA）治疗腹泻型肠易激综合征（IBS-D）大鼠模型的作用机制。

方法：采用累积对数浓度（3×10 mol/L 至 1×10 mol/L）研究 PA 对结肠自发性运动的影响。然后，我们测定了大鼠近端和远端结肠段对以下刺激的反应：（1）乙酰胆碱（1×10 mol/L 至 1×10 mol/L）；（2）神经递质拮抗剂，包括 N-硝基-L-精氨酸甲酯盐酸盐（10 μmol/L）和（1R*，2S*）-4-[2-碘-6-（甲氨基）-9H-嘌呤-9-基]-2-（膦酸氧基）双环[3.1.0]己烷-1-甲醇二氢磷酸酯四铵盐（1 μmol/L）；（3）激动剂 α，β-亚甲基腺苷 5'-三磷酸三钠盐（100 μmol/L）；（4）单剂量 KCl（120 mmol/L）。我们还通过用 PA（100 μmol/L）预处理 1 分钟来评估拮抗剂反应的阻滞剂的作用。采用电刺激（40 V、2-30 Hz、0.5 ms 脉冲持续时间和 10 s）观察 IBS-D 大鼠结肠中的非肾上腺素能、非胆碱能神经递质释放。还测定了 Krebs 溶液中的 ATP 水平。

结果：PA 对结肠纵行平滑肌的自发性收缩呈浓度依赖性抑制作用，半数有效浓度（EC）为 41.9 μmol/L。与 KCl 处理的 IBS-D 组相比，PA+KCl 处理的 IBS-D 组（11.87±3.34）的收缩反应（mg 收缩）在峰值张力方面明显降低（<0.01）。与 CCh 处理的 IBS-D 大鼠结肠相比，PA（EC=37.43 μmol/L）明显降低了 IBS-D 大鼠结肠平滑肌的胆碱能收缩反应（EC=0.94 μmol/L）（<0.05）。应激诱导的 IBS-D 大鼠中缺乏硝化能神经递质释放，对结肠平滑肌有收缩作用。PA 预处理对 L-NAME 诱导的收缩（10 μmol/L）有抑制作用（<0.05）。ATP 可能不是 PA 引起应激诱导的 IBS-D 大鼠结肠松弛的抑制作用的主要神经递质。

结论：PA 的应用可能为 IBS-D 提供一种新的治疗方法。