Endoplasmic reticulum stress contributes to ischemia-reperfusion (I/R) injury in rodent and cell models. However, the contribution of endoplasmic reticulum stress in the pathogenesis of endothelial I/R injury in humans is unknown. We tested the hypothesis that compared with placebo, inhibition of endoplasmic reticulum stress via ingestion of tauroursodeoxycholic acid would prevent the attenuation of endothelium-dependent vasodilation following I/R injury. Twelve young adults (six women) were studied following ingestion of a placebo or 1,500 mg tauroursodeoxycholic acid (TUDCA). Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasonography) before and after I/R injury, which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Endothelium-independent vasodilation (glyceryl trinitrate-mediated vasodilation) was also assessed after I/R injury. Compared with placebo, TUDCA ingestion increased circulating plasma concentrations by 145 ± 90 ng ml^-1 and increased concentrations of the taurine unconjugated form, ursodeoxycholic acid by 560 ± 156 ng ml^-1 (both P < 0.01). Ischemia-reperfusion injury attenuated endothelium-dependent vasodilation, an effect that did not differ between placebo (pre-I/R, 5.0 ± 2.1% vs. post-I/R 3.5 ± 2.2%) and TUDCA (pre-I/R, 5.6 ± 2.1% vs. post-I/R 3.9 ± 2.1%; P = 0.8) conditions. Similarly, endothelium-independent vasodilation did not differ between conditions (placebo, 19.6 ± 4.8% vs. TUDCA, 19.7 ± 6.1%; P = 0.9). Taken together, endoplasmic reticulum stress does not appear to contribute to endothelial I/R injury in healthy young adults.

中文翻译：

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内质网应激对人内皮缺血再灌注损伤的影响

内质网应激有助于啮齿动物和细胞模型的缺血再灌注 (I/R) 损伤。然而，内质网应激在人类内皮 I/R 损伤发病机制中的作用尚不清楚。我们测试了这样一个假设，即与安慰剂相比，通过摄入牛磺熊去氧胆酸抑制内质网应激将防止 I/R 损伤后内皮依赖性血管舒张的减弱。在摄入安慰剂或 1,500 毫克牛磺熊去氧胆酸 (TUDCA) 后，对 12 名年轻成人（6 名女性）进行了研究。在 I/R 损伤之前和之后，通过肱动脉血流介导的扩张（双工超声检查）评估内皮依赖性血管舒张，其由 20 分钟的手臂缺血和 20 分钟的再灌注诱导。I/R 损伤后还评估了不依赖于内皮的血管舒张（三硝酸甘油酯介导的血管舒张）。与安慰剂相比，TUDCA 摄入使循环血浆浓度增加了 145 ± 90 ng ml^-1并且牛磺酸未结合形式熊去氧胆酸的浓度增加了 560 ± 156 ng ml ^-1（均 P < 0.01）。缺血再灌注损伤减弱了内皮依赖性血管舒张，这种作用在安慰剂（I/R 前，5.0 ± 2.1% 与 I/R 后 3.5 ± 2.2%）和 TUDCA（I/R 前， 5.6 ± 2.1% 与 I/R 后 3.9 ± 2.1%；P = 0.8) 条件。同样，内皮非依赖性血管舒张在不同条件下也没有差异（安慰剂，19.6 ± 4.8% 与 TUDCA，19.7 ± 6.1%；P = 0.9）。总之，内质网应激似乎不会导致健康年轻人的内皮 I/R 损伤。