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Abstract <p>Metabolic imbalance in diabetes mellitus is a major causeof vascular complications leading to the development of hypoxia,which is one of the pathogenetic factors of neurodegenerative diseasesand diabetic encephalopathy. Disorders in gut–brain relationshipare thought to be an important aspect in the development of thispathology. In this context, correcting intestinal function via oraladministration of a sorbent may influence the functional state ofthe brain and the development of neurodegeneration. The aim of thisstudy was to identify the effect of a composite sorbent based onaluminum oxide and polydimethylsiloxane (Al<sub>2</sub>O<sub>3</sub>-PDMS)on the morphofunctional state of Virchow–Robin spaces and the expressionlevel of the lymphatic vessel endothelial hyaluronan 1 (LYVE-1)receptor, which are indicators of the glymphatic system status,as well as on the expression of hypoxia-inducible factor 1-alpha(HIF-1α) as one of the indicators of hypoxia development, in thebrain of <i>db</i>/<i>db</i> mice—a genetic model of type 2diabetes mellitus. The sorbent (0.665 g/kg in 200 µL of distilledwater) was administered intragastrically (i.g.) to 14-week-old female <i>db</i>/<i>db</i> micevia a gavage once daily for 7 days. The comparison groups consistedof female placebo (200 µL of water daily for 7 days, i.g.) and intactanimals. LYVE-1 and HIF-1α were detected immunohistochemically usingthe indirect avidin-biotin peroxidase method. It was found thati.g. Al<sub>2</sub>O<sub>3</sub>-PDMS administrationled to a reduction in edema of Virchow–Robin spaces in the brain’sglymphatic system around pre- and postcapillary microvessels, as wellas to a decrease in the relative areas of LYVE-1 expression (comparedto controls) and HIF-1α expression (compared to placebo) in braincells. Thus, oral administration of the Al<sub>2</sub>O<sub>3</sub>-PDMSsorbent exerts an anti-hypoxic effect on the brain cells of <i>db</i>/<i>db</i> mice,as evidenced by the decreased expression of HIF-1α, and promotesnormalization of fluid homeostasis in the brain, as indicated bythe narrowing of Virchow–Robin spaces around pre- and postcapillarymicrovessels and the depletion of the pool of LYVE-1-positive perivascularmacrophages.</p>

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Effect of Aluminum Oxide-Polydimethylsiloxane Composite Sorbent on LYVE-1 and HIF-1α Expression in the Brain of db/db Mice

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • S. V. Michurina,
  • A. E. Serykh,
  • I. Yu. Ishchenko,
  • S. A. Arkhipov,
  • A. Y. Letyagin,
  • M. A. Korolev,
  • L. N. Rachkovskaya,
  • E. L. Zavyalov

摘要

Abstract

Metabolic imbalance in diabetes mellitus is a major causeof vascular complications leading to the development of hypoxia,which is one of the pathogenetic factors of neurodegenerative diseasesand diabetic encephalopathy. Disorders in gut–brain relationshipare thought to be an important aspect in the development of thispathology. In this context, correcting intestinal function via oraladministration of a sorbent may influence the functional state ofthe brain and the development of neurodegeneration. The aim of thisstudy was to identify the effect of a composite sorbent based onaluminum oxide and polydimethylsiloxane (Al2O3-PDMS)on the morphofunctional state of Virchow–Robin spaces and the expressionlevel of the lymphatic vessel endothelial hyaluronan 1 (LYVE-1)receptor, which are indicators of the glymphatic system status,as well as on the expression of hypoxia-inducible factor 1-alpha(HIF-1α) as one of the indicators of hypoxia development, in thebrain of db/db mice—a genetic model of type 2diabetes mellitus. The sorbent (0.665 g/kg in 200 µL of distilledwater) was administered intragastrically (i.g.) to 14-week-old female db/db micevia a gavage once daily for 7 days. The comparison groups consistedof female placebo (200 µL of water daily for 7 days, i.g.) and intactanimals. LYVE-1 and HIF-1α were detected immunohistochemically usingthe indirect avidin-biotin peroxidase method. It was found thati.g. Al2O3-PDMS administrationled to a reduction in edema of Virchow–Robin spaces in the brain’sglymphatic system around pre- and postcapillary microvessels, as wellas to a decrease in the relative areas of LYVE-1 expression (comparedto controls) and HIF-1α expression (compared to placebo) in braincells. Thus, oral administration of the Al2O3-PDMSsorbent exerts an anti-hypoxic effect on the brain cells of db/db mice,as evidenced by the decreased expression of HIF-1α, and promotesnormalization of fluid homeostasis in the brain, as indicated bythe narrowing of Virchow–Robin spaces around pre- and postcapillarymicrovessels and the depletion of the pool of LYVE-1-positive perivascularmacrophages.