半胱胺通过增强细胞内硫醇活性减轻肠系膜动脉闭塞引起的肠再灌注损伤。

IF 1.7 Q3 PHARMACOLOGY & PHARMACY Drug Research Pub Date : 2023-03-01 DOI:10.1055/a-1974-9132
Babatunde Alabi, Olugbenga Iwalewa, Temidayo Omobowale, Adeolu Adedapo, Opeyemi Hammed, Richard Ajike, Oladele Afolabi
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引用次数: 1

摘要

背景:已有报道称,缺血/再灌注可进一步损害肠再灌注损伤(IRI),并通过氧化应激、炎症和细胞凋亡引起多远端脏器功能障碍。已知半胱胺可抑制氧化应激、炎症细胞因子和细胞凋亡。方法:将32只Wistar大鼠分为4组:假手术组、肠再灌注损伤组、50 mg/kg和100 mg/kg半胱胺治疗IRI组。取回肠末端5cm段沿肠系膜顺时针旋转360°45分钟,诱导缺血后扭转。腐烂4小时后保存组织进行生化评价和组织学检查。测定GPx、GSH、蛋白和非蛋白硫醇、H2O2、MDA的活性。测定血清亚硝酸盐、MPO、ALT、AST、tnf - α和IL-6的浓度。免疫组织化学检测Caspase 3和bax。50和100 mg/kg半胱胺可逆转IRI大鼠GPx、GSH、蛋白硫醇和非蛋白硫醇的降低,但p2O2、MDA和亚硝酸盐均有统计学意义。血清MPO、TNF-α、il - 6、AST和ALT在IRI中显著升高,而半胱胺处理大鼠在IRI中显著降低(p结论:半胱胺通过增强细胞内抗氧化防御系统,抑制炎症介质和肠组织促凋亡蛋白的表达来减轻IRI。
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Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.

Background: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H2O2, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H2O2, MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers.

Conclusion: Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.

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来源期刊
Drug Research
Drug Research PHARMACOLOGY & PHARMACY-
CiteScore
3.50
自引率
0.00%
发文量
67
期刊介绍: Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.
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