Brooks Belinda, Delaney-Robinson Carol, Molyneaux Lynda, Yue Dennis K
Diabetes Centre, Royal Prince Alfred Hospital, and Discipline of Medicine, The University of Sydney, Sydney, New South Wales, Australia.
J Diabetes Complications. 2008 Mar-Apr;22(2):88-95. doi: 10.1016/j.jdiacomp.2007.07.002.
This article aims to study the effects of ruboxistaurin (RBX) on skin microvascular blood flow (SkBF) and evaluate the relationship between endothelial and neural control of SkBF in patients with diabetic peripheral neuropathy (DPN).
We studied 11 placebo- and 9 RBX (32 mg/day)-treated patients who participated in a 1-year, double-masked, randomized, Phase 3 study of RBX for treatment of DPN sensory symptoms. Patients had type 1 or type 2 diabetes, a detectable sural sensory nerve action potential, and Neuropathy Total Symptom Score-6 (NTSS-6) >6 points. SkBF was measured by laser Doppler velocimetry, combined with iontophoresis of acetylcholine and sodium nitroprusside, at baseline, 3 months, and 1 year. Sensory symptoms and electrophysiology were also evaluated during the study. The relationship between endothelial and neural control of SkBF at baseline was assessed using linear regression.
No significant differences (RBX vs. placebo) were demonstrable for post-iontophoresis SkBF [fold increase from basal state (1 year): endothelium-dependent, 3.6 vs. 8.6; endothelium-independent, 3.7 vs. 2.0; C fiber-mediated, 1.7 vs. 2.0; P>.05] or sensory symptoms [NTSS-6 total score (1 year): 7.7 vs. 6.0 points; P=.4]. There were also no significant between-group differences in nerve conduction parameters, except for placebo peroneal nerve conduction velocity, which demonstrated a statistically significant improvement of unknown clinical importance (Z=2.1; P=.034). At baseline, C fiber-mediated vasodilatation correlated well with endothelium-dependent vasodilation (r=.7, P<.01) but not with endothelium-independent vasodilatation (r=-.1, P=.7).
RBX demonstrated no effect on SkBF or sensory symptoms after 1 year in this cohort. The correlation between C fiber-mediated and endothelium-dependent SkBF at baseline suggests that improving endothelial function could affect the microcirculation not only locally but also via the neurovascular arcade.
本文旨在研究鲁伯斯塔林（RBX）对皮肤微血管血流量（SkBF）的影响，并评估糖尿病周围神经病变（DPN）患者中SkBF的内皮控制与神经控制之间的关系。
我们研究了11名接受安慰剂治疗和9名接受RBX（32毫克/天）治疗的患者，这些患者参与了一项为期1年的、双盲、随机的3期研究，该研究旨在探讨RBX治疗DPN感觉症状的效果。患者患有1型或2型糖尿病，可检测到腓肠感觉神经动作电位，且神经病变总症状评分-6（NTSS-6）>6分。在基线、3个月和1年时，通过激光多普勒测速法结合乙酰胆碱和硝普钠的离子导入来测量SkBF。在研究期间还评估了感觉症状和电生理情况。使用线性回归评估基线时SkBF的内皮控制与神经控制之间的关系。
离子导入后SkBF[从基础状态增加的倍数（1年）]或感觉症状[NTSS-6总分（1年）]在RBX组与安慰剂组之间无显著差异[内皮依赖性：3.6对8.6；非内皮依赖性：3.7对2.0；C纤维介导：1.7对2.0；P>.05]或[NTSS-6总分（1年）：7.7对6.0分；P=0.4]。除安慰剂组腓总神经传导速度有统计学上显著改善（临床意义不明）（Z=2.1；P=0.034）外，神经传导参数在组间也无显著差异。在基线时，C纤维介导的血管舒张与内皮依赖性血管舒张相关性良好（r=0.7，P<0.01），但与非内皮依赖性血管舒张无相关性（r=-0.1，P=0.7）。
在该队列中，1年后RBX对SkBF或感觉症状无影响。基线时C纤维介导的SkBF与内皮依赖性SkBF之间的相关性表明，改善内皮功能不仅可局部影响微循环，还可通过神经血管连接影响微循环。
