Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences69825410.7868/S2658655X25110062EXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleA Comparison of Changes in the Portal Vein and Hepatic Artery during Portal Hypertension Induced by Common Bile Duct Ligation in MiceСРАВНЕНИЕ ИЗМЕНЕНИЙ В ПОРТАЛЬНОЙ ВЕНЕ И ПЕЧЕНОЧНОЙ АРТЕРИИ У МЫШЕЙ ПРИ ПОРТАЛЬНОЙ ГИПЕРТЕНЗИИ, ВЫЗВАННОЙ ПЕРЕВЯЗКОЙ ОБЩЕГО ЖЕЛЧНОГО ПРОТОКАPechkovaM. GПечковаМ. Гmarta.peckovva@gmail.comKiryukhinaO. OКирюхинаО. ОBorzykhA. AБорзыхА. АTarasovaO. SТарасоваО. СInstitute of Biomedical Problems, Russian Academy of SciencesИнститут медико-биологических проблем РАНKharkevich Institute for Information Transmission Problems, Russian Academy of SciencesИнститут проблем передачи информации им. А.А. Харкевича РАНLomonosov Moscow State UniversityМосковский государственный университет имени М.В. Ломоносова1511202511111VOL 111, NO11 (2025)ТОМ 111, №11 (2025)1780179609122025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/698254

Portal hypertension (PH) develops in various liver diseases and is associated with impaired hepatic blood flow. The aim of this study was to compare the effects of PH on changes in the blood vessels supplying the liver – the portal vein and hepatic artery. In male C57Bl/61 mice, PH was induced by common bile duct ligation, while the control group underwent a sham operation. Three weeks later, the animals were euthanized, their organs (liver and spleen) were weighed, and samples of blood (for biochemical analysis) and liver tissue (for gene expression analysis using quantitative PCR) were collected. Additionally, the portal vein and hepatic artery were isolated for functional studies using an isometric wire myograph or for gene expression analysis. Liver pathology was confirmed by an increase in liver weight relative to body weight, alterations in blood biochemical parameters (elevated ALT and alkaline phosphatase activity, increased levels of total bilirubin, direct bilirubin, and total cholesterol), and upregulation of fibrosis-associated genes (Acta2 and Mmp9). Spleen weight was increased in bile duct-ligated mice compared to the control group, which is typical of PH. The portal vein in PH mice showed an increased maximal contractile response to U46619 (a thromboxane A2 receptor agonist), along with decreased sensitivity to this agonist, reduced acetylcholine-induced relaxation, and enhanced sensitivity to nitric oxide. Furthermore, ATP-induced contractile responses were attenuated, which was accompanied by an increase in the expression of genes involved in purinergic signaling (Panx1, P2rx1, P2rx4, and Nt5e). No significant functional changes were observed in the hepatic artery of PH mice. These findings suggest that the portal vein is predominantly affected at the early stages of PH and underscore its central role in the vascular dysfunction associated with liver pathology.

Портальная гипертензия (ПГ) развивается при различных заболеваниях печени и сопровождается нарушениями кровоснабжения этого органа. Целью данной работы стало сравнение влияния ПГ на изменения сосудов, которые приносят кровь в печень – портальной вены и печеночной артерии. У самцов мышей C57Bl/бJ моделировали ПГ путем перевязки общего желчного протока, в контрольной группе проводили ложную операцию. Спустя три недели животных подвергали эвтаназии, взвешивали органы (печень и селезенку), брали образцы крови (для биохимических анализов) и печени (для исследования экспрессии генов методом количественной ПЦР). Кроме того, выделяли портальную вену и печеночную артерию для исследования реакций в изометрическом миографе или анализа экспрессии генов. Развитие печеночной патологии было подтверждено по увеличению массы печени (относительно массы тела), изменениям показателей биохимии крови (увеличение активности АЛТ и щелочной фосфатазы, содержания общего билирубина, прямого билирубина и общего холестерина) и повышению экспрессии генов-маркеров фиброза ткани (Acta2 и Mmp9). Масса селезенки у мышей с перевязкой желчного протока была увеличена по сравнению с контрольной группой, что характерно для ПГ. Портальная вена мышей с ПГ демонстрировала увеличение максимального сократительного ответа на U46619 (агонист рецепторов тромбоксана А2) и одновременно снижение чувствительности к этому агонисту, уменьшение ацетилхолин-опосредованного расслабления и повышение чувствительности к оксиду азота. Также наблюдалось снижение сократительных ответов вены на АТФ, которое сопровождалось повышением экспрессии генов, кодирующих белки пуринергической сигнальной системы (Panx1, P2rx1, P2rx4 и Nt5e). В печеночной артерии мышей с ПГ значимых функциональных изменений выявлено не было. Полученные данные свидетельствуют о преимущественном вовлечении портальной вены на ранних стадиях ПГ и подчеркивают ее ключевую роль в сосудистой дисфункции при патологиях печени.

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