Effects of Lupeol on Intestinal Anastomosis After Experimental Intestinal Ischemia-Reperfusion Injury in Rats.

IF 5.1 2区 医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S501289
Cem Kaya, Alparslan Kapisiz, Sibel Eryilmaz, Ramazan Karabulut, Zafer Turkyilmaz, Mehmet Arda Inan, Gizem Yaz Aydin, Mert Alperen Celik, Kaan Sonmez
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Abstract

Background: Intestinal ischemia/reperfusion (I/R) injury can occur in a wide variety of diseases and surgeries. If necessary, the blood flow should be restored, including re-anastomosis by removing the intestines with impaired circulation. In this process, anastomotic strength is as important as inflammatory responses and oxidative stress. Therefore, we conducted the study to investigate the effects of lupeol on intestinal ischemia-reperfusion injury, not only biochemically and histopathologically but also on anastomotic strength and miRNAs.

Methods: Female rats were randomly divided into six groups. While only laparotomy was performed in the control group (Group C), anastomosis was performed in the sham group (Group S). In the other groups, the superior mesenteric artery was clamped for 45 minutes. In the groups I/R1 and L1, the intestine was transected, and end-to-end anastomosis was performed at the 1st hour of reperfusion. In the groups I/R24 and L24, this procedure was performed at the 24th hour of reperfusion. In addition, lupeol treatment was given before reperfusion and for the following 4 days in the groups L1 and L24. All rats, except the control group, bursting pressure was measured on the 5th day of anastomosis, and then all rats including the control group were sacrificed. TNF-α, IL-6 levels in blood samples and MDA, GSH, caspase-3, miR-29b-3p, miR-34a-5p, miR-495-3p levels in intestinal tissues were measured, and intestinal histopathology was also examined.

Results: Lupeol treatment, which was statistically significant in some parameters, demonstrated positive effects by decreasing TNF, IL-6, MDA, caspase-3, histopathological damage levels and increasing GSH and bursting pressure. In addition, lupeol decreased miR-34a-5p expression and increased miR-29b-3p and miR-495-3p expression.

Conclusion: Lupeol protected the intestines from I/R damage with its antioxidant and anti-inflammatory effects. Besides, it reduced the histopathological damage and increased the anastomotic strength. Additionally, miR-29b-3p, miR-34a-5p, miR-495-3p expressions were altered by lupeol.

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芦皮醇对实验性肠缺血再灌注损伤大鼠肠吻合的影响。
背景:肠缺血/再灌注(I/R)损伤可发生在多种疾病和手术中。如有必要,应恢复血流,包括通过切除循环受损的肠道进行再吻合。在这个过程中,吻合口的强度与炎症反应和氧化应激同样重要。因此,我们通过生物化学和组织病理学研究芦皮醇对肠缺血再灌注损伤的影响,以及对吻合口强度和mirna的影响。方法:雌性大鼠随机分为6组。对照组(C组)仅开腹,假手术组(S组)吻合术,其余各组夹持肠系膜上动脉45分钟。I/R1组和L1组在再灌注1 h时切开肠,端对端吻合。在I/R24组和L24组,在再灌注24小时进行该手术。此外,L1组和L24组在再灌注前和再灌注后4 d给予鲁皮酮治疗。除对照组外,所有大鼠均于吻合后第5天测定破裂压力,并处死,对照组除外。检测血液样本中TNF-α、IL-6水平,肠组织中MDA、GSH、caspase-3、miR-29b-3p、miR-34a-5p、miR-495-3p水平,并检测肠道组织病理学。结果:芦皮醇治疗可降低TNF、IL-6、MDA、caspase-3及组织病理损伤水平,增加GSH和破裂压力,部分参数有统计学意义。此外,lupeol降低miR-34a-5p表达,升高miR-29b-3p和miR-495-3p表达。结论:芦皮醇具有抗氧化和抗炎作用,可保护肠道免受I/R损伤。减少了组织病理损伤,增加了吻合口强度。此外,lupeol可改变miR-29b-3p、miR-34a-5p、miR-495-3p的表达。
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来源期刊
Drug Design, Development and Therapy
Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY
CiteScore
9.00
自引率
0.00%
发文量
382
审稿时长
>12 weeks
期刊介绍: Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.
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