a Department of ICU , Shengli Oilfield Central Hospital , Dongying , China.
Pharm Biol. 2018 Dec;56(1):344-350. doi: 10.1080/13880209.2018.1478430.
Dihydromyricetin (DMY) has oxidation resistance, anti-inflammatory and free radical scavenging capabilities. The preventive effects of DMY for vascular hyporeactivity remain unclear.
This study investigates the preventive effects of DMY in vascular hyporeactivity.
The experimental sepsis was induced by transvenous administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. DMY-treated rats received daily administration of DMY, 5 μg/kg dissolved in DMSO through the tail vein for 7 days. The invasive mean arterial pressure (MAP) of the caudal ventral artery was measured. Dose-response curves for norepinephrine (NE, doses from 10 to 10M) were obtained in isolated thoracic aorta in a cumulative manner. The function of MaxiK and K channels were investigated using whole-cell patch clamp recording. The Elisa was adopted to measure the serum concentration of NO, MDA, 3-NT, IL-1β and TNF-α.
The increased MAP in septic rats induced by vasopressor agents was smaller than that in control rats. However, the % of increased MAP induced by vasopressor agents was raised by DMY injection (NE: 20.4 ± 8.495 vs. 15.16 ± 5.195%; AVP: 14.05 ± 2.459 vs. 9.583 ± 2.982%, p < 0.05). The vascular hyporesponsiveness to NE (10M) in vitro. was increased by 51% in LPS + DMY group compared with that in LPS + Con group (2.74 ± 0.81 vs. 1.82 ± 0.92 g, p < 0.05). Charybdotoxin (a potent MaxiK channel blocker) and glibenclamide (a K channel blocker) pretreatment, instead of 4-aminopyridine (4-AP) and BaCl, could diminish the DMY-induced improvement of vasoconstrictor hyporeactivity (ChTX: 73.2 ± 11.8 vs. 71.8 ± 13.5%; Glib: 63.1 ± 12.5 vs. 58.1 ± 13.7%, p > 0.05). DMY blunted the highly sensitized MaxiK and K channels of arterial smooth muscle cells isolated from the thoracic aorta of LPS rats. DMY decreased the serum level of NO, MDA, IL-1β and TNF-α, which had increased in LPS rats.
Our results indicate that DMY administration ameliorated the impaired contractility of the rat aorta in experimental sepsis. Such an effect is mediated by normalization of the over-excited MaxiK and K, channels possibly via oxidative stress inhibition.
二氢杨梅素（DMY）具有抗氧化、抗炎和自由基清除能力。DMY 对血管低反应性的预防作用尚不清楚。
本研究探讨 DMY 对血管低反应性的预防作用。
通过静脉内给予脂多糖（LPS）诱导 Sprague-Dawley（SD）大鼠实验性败血症。DMY 治疗组大鼠每天通过尾静脉给予 5μg/kg 的 DMY，溶于 DMSO 中，连续 7 天。测量尾腹侧动脉的侵入性平均动脉压（MAP）。采用累积方式获得离体胸主动脉中去甲肾上腺素（NE，剂量从 10 到 10M）的剂量反应曲线。使用全细胞膜片钳记录研究 MaxiK 和 K 通道的功能。采用 Elisa 法测定血清中 NO、MDA、3-NT、IL-1β 和 TNF-α 的浓度。
与对照组相比，败血症大鼠对血管加压剂诱导的 MAP 升高较小。然而，DMY 注射后，血管加压剂诱导的 MAP 升高百分比升高（NE：20.4±8.495%比 15.16±5.195%；AVP：14.05±2.459%比 9.583±2.982%，p<0.05）。体外 NE（10M）对血管的低反应性增加了 51%，与 LPS+Con 组相比，LPS+DMY 组增加了 2.74±0.81 比 1.82±0.92g（p<0.05）。与 4-氨基吡啶（4-AP）和 BaCl 相比，Charybdotoxin（一种强效的 MaxiK 通道阻断剂）和格列本脲（一种 K 通道阻断剂）预处理可减少 DMY 诱导的血管收缩低反应性改善（ChTX：73.2±11.8%比 71.8±13.5%；Glib：63.1±12.5%比 58.1±13.7%，p>0.05）。DMY 使 LPS 大鼠胸主动脉分离的动脉平滑肌细胞中高度敏化的 MaxiK 和 K 通道失活。DMY 降低了 LPS 大鼠血清中升高的 NO、MDA、IL-1β 和 TNF-α 的水平。
我们的结果表明，DMY 给药改善了实验性败血症大鼠主动脉收缩功能障碍。这种作用是通过抑制氧化应激来调节过度兴奋的 MaxiK 和 K 通道来实现的。
