Prostaglandin E1 regulates vascular-related factors and protects microcirculatory function during the acute phase of traumatic spinal cord injury

doi:10.12307/2025.203

Abstract

Abstract: BACKGROUND: Prostaglandin E1 (PGE1) has been shown to play a regulatory role in vasodilatation, inflammation, and leukocyte migration and adhesion, but its effects on spinal cord microcirculation after traumatic spinal cord injury (SCI) remain poorly understood.
OBJECTIVE: To investigate the mechanism underlying the protective effects of PGE1 administered during the acute phase of traumatic SCI in rats on the regulation of vascular-related factors and microcirculatory function.
METHODS: Seventy-two female Sprague-Dawley rats were divided into three groups (n=24 per group): control group, SCI group, and PGE1 group. An in vivo SCI model was established using Allen’s blow method. Rats in the PGE1 group were injected with PGE1 (10 µg/kg) via the tail vein immediately after SCI. Spinal cord microcirculatory blood flow and oxygen saturation, spinal cord microvessel diameter and area, spinal cord water content, vascular function regulators (von Willebrand factor, thromboxane A2, prostacyclin, endothelin-1), and inflammatory factors (tumor necrosis factor-α, interleukin-1β) were measured at 2 and 24 hours after SCI.
RESULTS AND CONCLUSION: At 2 hours after SCI, the diameter and area of spinal cord microvessels, spinal cord microcirculatory blood flow, and oxygen saturation in the PGE1 group were higher than those in the SCI group (P < 0.05), the water content of the spinal cord was lower than that in the SCI group
(P < 0.05), and the level of plasma von Willebrand Factor, the ratio of thromboxane A2/prostacyclin of the spinal cord and the level of endothelin-1 were lower than those in the SCI group (P < 0.05). At 24 hours after SCI, the spinal cord microvessel area, blood flow, and oxygen saturation of rats in the PGE1 group were higher than those in the SCI group (P < 0.05), the spinal cord water content was lower than that in the SCI group (P < 0.05), and the levels of plasma von Willebrand factor, spinal cord tissue thromboxane A2/prostacyclin ratio and the levels of endothelin-1, tumor necrosis factor-α and interleukin-1β were lower than those in the SCI group (P < 0.05). The diameter and area of spinal cord microvessels, spinal cord microcirculatory blood flow and blood oxygen saturation of rats in the SCI group were higher than those in the SCI group at 24 hours post-injury (P < 0.05), and the levels of plasma von Willebrand factor, spinal tissue thromboxane A2/prostacyclin ratio, tumor necrosis factor-α and interleukin-1β were higher than those at 2 hours post-injury (P < 0.05), but the level of endothelin-1 in spinal cord tissue was lower than that at 2 hours (P < 0.05). The blood flow and oxygen saturation of spinal cord microcirculation in the PGE1 group rats at 24 hours post-injury were lower than those at 2 hours post-injury (P < 0.05), and the diameter and area of spinal cord microvessels and water content of the spinal cord were higher than those at 2 hours post-injury (P < 0.05). The above results indicate that intravenous administration of PGE1 in SCI rats immediately after injury can regulate vascular function regulators, inflammatory factors and improve microcirculation of the spinal cord after SCI, which provides a potential basis for the search of drugs for the treatment of acute SCI.

Key words: spinal cord injury, prostaglandin E1, spinal cord microcirculation, microcirculatory disorder, inflammatory factor, vascular function regulator

CLC Number:

Wang Rongrong, Huang Yushan, Li Xiangmiao, Bai Jinzhu. Prostaglandin E1 regulates vascular-related factors and protects microcirculatory function during the acute phase of traumatic spinal cord injury [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(5): 958-967.

Figures/Tables 7

2.1 实验动物数量分析 72只雌性 SD 大鼠随机分为假手术组、脊髓损伤组、前列腺素E1组，每组 24 只。所有大鼠均未死亡，全部进入结果分析。 2.2 前列腺素E1增加微血管直径及面积，改善脊髓微循环血流量和血氧饱和度为了评估各组大鼠的脊髓微循环血流动力学，此次研究利用激光多普勒血流仪检测脊髓损伤后2，24 h时的脊髓微循环血流量(图2A)及血氧饱和度(图2B)。与对照组大鼠比较，脊髓损伤组大鼠脊髓微循环血流量及血氧饱和度在损伤后显著下降(P < 0.001)；在脊髓损伤组内比较发现，与损伤后2 h相比，损伤后24 h脊髓微循环血流量及血氧饱和度更高(P < 0.001)。说明脊髓损伤降低脊髓微循环血流量及血氧饱和度，且脊髓损伤后脊髓微循环血流量及血氧饱和度在24 h有一定程度的自行恢复。与脊髓损伤组大鼠比较，前列腺素E1组大鼠脊髓微循环血流量及血氧饱和度在损伤后2，24 h均有部分恢复(P < 0.001)；在前列腺素E1组内比较发现，与损伤后2 h相比，损伤后24 h脊髓微循环血流量及血氧饱和度降低(P < 0.001)。说明脊髓损伤后即刻尾静脉注射前列腺素E1可改善脊髓微循环血流量及血氧饱和度，但药效会随着时间延长减弱。为了评估各组大鼠脊髓微循环的血管形态学，此次研究利用单宁酸-氯化铁染色测定脊髓损伤后2，24 h时的脊髓微循环血管直径及面积(图2C-E)。与假手术组比较，脊髓微循环血管直径在脊髓损伤后2 h(P < 0.001)和24 h(P < 0.01)明显下降，血管面积在脊髓损伤后2，24 h显著降低(P < 0.001)；在脊髓损伤组内比较发现，与损伤后2 h比较，损伤后24 h时血管直径和面积有所增加(P < 0.001)。表明脊髓损伤后脊髓微循环的血管直径及面积减小，但是在脊髓损伤后24 h时血管直径和面积有一定恢复。与脊髓损伤组大鼠比较，前列腺素E1组大鼠在损伤后2 h脊髓微循环血管直径(P < 0.001)和面积(P < 0.001)增加，但在损伤后24 h血管直径无统计学差异(P > 0.05)，血管面积有所增加(P < 0.001)；在前列腺素E1组内比较发现，与损伤后2 h时比较，损伤后24 h时的血管直径(P < 0.05)及面积(P < 0.01)更大。见表1。"

2.3 前列腺素E1减轻脊髓水肿，减少脊髓组织结构的损伤用干/湿重比法评估脊髓损伤及前列腺素E1对脊髓水肿的影响(图3A)。结果表明，脊髓损伤组含水量在损伤后2，24 h均高于假手术组(2 h：P < 0.01；24 h：P < 0.001)；但在脊髓损伤组内比较发现，损伤后2，24 h两个时间点的含水量没有差异(P > 0.05)。静脉注射前列腺素E1可减轻脊髓损伤后脊髓水肿，降低脊髓含水量(2 h：P < 0.01；24 h：P < 0.01)；在前列腺素E1组内比较发现，与损伤后2 h时比较，损伤后24 h时脊髓含水量更高(P < 0.05)。组织病理学检查显示，对照组脊髓结构完整，没有出血、坏死或者炎症浸润；而脊髓损伤组大鼠损伤2 h后，脊髓结构破坏，神经元损伤，灰质发生出血，血管的周围组织有炎症细胞浸润现象；24 h后，脊髓灰质出血严重，部分神经元坏死，血管周围组织的炎症细胞浸润现象加重。脊髓损伤后使用前列腺素E1干预，相对于脊髓损伤组，出血、神经元损伤和炎症有所减轻。见图3B。 2.4 前列腺素E1下调血浆血管性血友病因子、脊髓组织中内皮素1的表达及血栓素A2/前列环素比值为了评估脊髓损伤后血管调节因子变化及前列腺素E1对血管调节因子的影响，此次研究利用ELISA法定量测定脊髓损伤后2，24 h时的血管调节因子含量变化(表2)。ELISA检测结果显示，与对照组大鼠比较，脊髓损伤组大鼠血浆血管性血友病因子(2 h：P < 0.001；24 h：P < 0.05)、脊髓组织中内皮素1(2 h： P < 0.001；24 h：P < 0.001)及血栓素A2/ 前列环素比值(2 h：P < 0.05；24 h：P < 0.01)在损伤后2，24 h时显著增加。在脊髓损伤组内比较发现，与损伤后2 h比较，损伤后24 h血浆血管性血友病因子含量(P < 0.05)及脊髓组织中血栓素A2/ 前列环素比值(P < 0.01)更高，而脊髓组织中内皮素1含量下降(P < 0.01)。与脊髓损伤组大鼠比较，前列腺素E1组大鼠在损伤后2，24 h血浆血管性血友病因子(2 h：P < 0.05；24 h：P < 0.05)、脊髓组织中内皮素1表达(2 h：P < 0.001；24 h：P < 0.05)及血栓素A2/ 前列环素比值(2 h：P < 0.01；24 h：P < 0.05)降低。在前列腺素E1组内比较发现，2个时间点的血浆血管性血友病因子含量(P > 0.05)、脊髓组织内皮素1含量(P > 0.05)及血栓素A2/ 前列环素比值(P > 0.05)均无统计学差异。"

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