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间质干细胞治疗肠缺血再灌注损伤:临床前研究的系统评价和荟萃分析。

Mesenchymal stem cells against intestinal ischemia-reperfusion injury: a systematic review and meta-analysis of preclinical studies.

机构信息

The First Clinical Medical College, Lanzhou University, No. 199, Donggang Road West, Chengguan District, Lanzhou, Gansu, China.

The Department of Anesthesiology, Gansu Provincial Maternity and Child-Care Hospital, No. 143, Qilihe North Street, Qilihe District, Lanzhou, Gansu, China.

出版信息

Stem Cell Res Ther. 2022 May 26;13(1):216. doi: 10.1186/s13287-022-02896-y.

Abstract

BACKGROUND

Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments.

METHODS

We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3.

RESULTS

It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells.

CONCLUSIONS

Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

摘要

背景

肠缺血再灌注损伤(IRI)会导致局部和远处组织损伤。多器官衰竭是严重肠 IRI 的常见并发症,导致其发病率和死亡率较高。到目前为止,这种情况还没有得到很好的治疗,因此迫切需要新的更有效的治疗方法。本研究通过多项动物实验评估了间充质干细胞(MSCs)治疗对肠 IRI 的有益作用。

方法

我们从 4 个数据库(Pubmed、Embase、Cochrane 图书馆和 Web of science)进行了全面的文献检索。主要结局包括生存率、Chiu 评分、肠组织中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和丙二醛(MDA)水平,以及血清中二胺氧化酶(DAO)、D-乳酸和 TNF-α水平。使用 Review Manager 5.3 进行统计分析。

结果

最终有 18 项符合条件的研究纳入分析。我们表明,与对照组相比,肠 IRI 后动物的生存率在 MSC 治疗后更高。此外,MSC 治疗减轻了 IRI 引起的肠道损伤,表现为 Chiu 评分降低(-1.96,95%CI-2.72 至-1.19,P<0.00001),肠道炎症减少(IL-6:-2.73,95%CI-4.19 至-1.27,P=0.0002),TNF-α:-3.00,95%CI-4.74 至-1.26,P=0.0007)和氧化应激(MDA:-2.18,95%CI-3.17 至-1.19,P<0.0001),血清中 DAO(-1.39,95%CI-2.07 至-0.72,P<0.0001)、D-乳酸(-1.54,95%CI-2.18 至-0.90,P<0.00001)和 TNF-α(-2.42,95%CI-3.45 至-1.40,P<0.00001)水平降低。MSC 治疗肠 IRI 的可能机制可能是通过减少炎症、减轻氧化应激,以及抑制肠道上皮细胞的凋亡和焦亡。

结论

综上所述,这些研究表明,MSC 可能是一种有前途的治疗肠 IRI 的新方法,其机制可能与炎症、氧化应激、凋亡和焦亡有关。然而,还需要进一步的研究来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5072/9137086/b6688e9381cf/13287_2022_2896_Fig1_HTML.jpg

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