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利用间充质干细胞分泌组改善脓毒症急性肾损伤小鼠的肾功能

Improvement of renal functions in mice with septic acute kidney injury using secretome of mesenchymal stem cells.

作者信息

Arifin Arifin, Purwanto Bambang, Indarto Dono, Wasita Brian, Sumanjar Tatar, Pamungkasari Eti Poncorini, Soetrisno Soetrisno

机构信息

Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir Sutami No 36A, Kentingan, Jebres, Surakarta 57126, Indonesia.

Department of Internal Medicine, Faculty of Medicine, Universitas Sebelas Maret/General Hospital Dr. Moewardi, Jl. Kolonel Sutarto No. 132, Jebres, Surakarta 57126, Indonesia.

出版信息

Saudi J Biol Sci. 2024 Mar;31(3):103931. doi: 10.1016/j.sjbs.2024.103931. Epub 2024 Jan 13.

Abstract

BACKGROUND

A potentially fatal complication of sepsis is septic acute kidney injury. Stem cell therapy is a potential new method of treating sepsis and has been applied to treat some human diseases.

OBJECTIVES

This study investigated the effects of secretome-MSCs on NGAL, CRP, NF-κB, and MMP-9 proteins, and histopathology in mice with septic AKI.

METHODS

A post-test-only group design was conducted in 30 Balb/C male mice, which were randomly assigned to five groups: the control group was intraperitoneally injected with 0.5 ml of 0.9 % NaCl, the septic AKI, and the treatment groups (T1, T2, and T3) were intraperitoneally injected with 0.5 ml of 0.9 % NaCl and 0.3 mg/kg BW LPS single dose for three days. Three-day treatments of 150, 300, and 600 µl secretome-MSCs were administered intraperitoneally into the treatment groups. Furthermore, kidney and blood samples were collected for biochemical and histopathological analyses.

RESULTS

The T1, T2, and T3 groups had lower expression of NF-κB and MMP-9 and significantly lower CRP and NGAL levels than that of septic AKI group. T1 (1.21 ± 0.19), T2 (0.75 ± 0.22), and T3 (0.38 ± 0.14) groups demonstrated lower average scores for inflammation, necrosis, hemorrhage, and degeneration compared to septic AKI group (2.17 ± 0.13).

CONCLUSIONS

Administration of 600 µl/20 g BW secretome-MSCs suppresses NF-κB and MMP-9 expression and reduces CRP and NGAL levels. Meanwhile, the 150 and 300 µl/20 g BW doses also indicated a greater improvement in renal tissue damage of mice with septic AKI.

摘要

背景

脓毒症的一种潜在致命并发症是脓毒性急性肾损伤。干细胞疗法是一种治疗脓毒症的潜在新方法,已应用于治疗一些人类疾病。

目的

本研究调查了分泌组间充质干细胞对脓毒性急性肾损伤小鼠中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、C反应蛋白(CRP)、核因子κB(NF-κB)和基质金属蛋白酶-9(MMP-9)蛋白以及组织病理学的影响。

方法

对30只雄性Balb/C小鼠采用仅后测组设计,将其随机分为五组:对照组腹腔注射0.5 ml 0.9%氯化钠溶液,脓毒性急性肾损伤组以及治疗组(T1、T2和T3)腹腔注射0.5 ml 0.9%氯化钠溶液和0.3 mg/kg体重的脂多糖单剂量,持续三天。治疗组腹腔注射150、300和600 μl分泌组间充质干细胞进行为期三天的治疗。此外,收集肾脏和血液样本进行生化和组织病理学分析。

结果

T1、T2和T3组的NF-κB和MMP-9表达较低,且CRP和NGAL水平明显低于脓毒性急性肾损伤组。与脓毒性急性肾损伤组(2.17±0.13)相比,T1组(1.21±0.19)、T2组(0.75±0.22)和T3组(0.38±0.14)在炎症、坏死、出血和变性方面的平均评分较低。

结论

腹腔注射600 μl/20 g体重的分泌组间充质干细胞可抑制NF-κB和MMP-9表达,降低CRP和NGAL水平。同时,150和300 μl/20 g体重的剂量也表明对脓毒性急性肾损伤小鼠的肾组织损伤有更大改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a462/10831246/90862d6877ee/gr1.jpg

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