Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

Abstract Background: Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group.Conclusion: BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

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Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats

10.21203/rs.3.rs-227211/v1 ◽

2021 ◽

Author(s):

Hu Tian ◽

Wan-song Zhang ◽

Cheng Yang ◽

Jun-hao Zhou ◽

Ran-ran Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Stem Cell ◽

Treatment Group ◽

Mesenchymal Stem Cell ◽

Reperfusion Injury ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Testicular Ischemia

Abstract Background Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury. Methods Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group. Conclusion BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。

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The long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

10.21203/rs.3.rs-79465/v1 ◽

2020 ◽

Author(s):

Bomi Kim ◽

EunHye Lee ◽

BoHyun Yoon ◽

So Young Chun ◽

Jae-Wook Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Reperfusion Injury ◽

Rat Model ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Group A ◽

Testicular Ischemia

Abstract Background Testicular torsion is a urological emergency in which misdiagnosis and inappropriate treatment can lead to testicular atrophy and male infertility owing to ischemia-reperfusion injury (IRI). Although experimental studies of testicular torsion have been preceded, promising therapeutic agents based on the long-term effect for spermatogenesis have not been identified in testicular ischemia reperfusion injury (IRI) animal model. Tadalafil, one of the phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against IRI in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model. Methods Forty-eight adolescent Sprague–Dawley rats were divided into 6 groups (A-F). Sham operation was performed in group A. Group B received surgical 720-degree torsion of the left testis without any medication. Groups C, D, E, and F were operated surgical torsion with tadalafil at varying doses (0.3 mg/kg, 1.0 mg/kg) and durations (single or daily administration for 4 weeks). Detorsion was performed after 3 hour of torsion in all rats except the sham group. Four weeks after operation, both testes were evaluated of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C. Results For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts. The groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration. Furthermore, molecular markers (MDA and SOD) related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration. Conclusion Tadalafil alleviated long-term deterioration of spermatogenesis and oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.

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Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miRNA-29c Decreases Cardiac Ischemia/Reperfusion Injury Through Inhibition of Excessive Autophagy via the PTEN/Akt/mTOR Signaling Pathway

Circulation Journal ◽

10.1253/circj.cj-19-1060 ◽

2020 ◽

Vol 84 (8) ◽

pp. 1304-1311 ◽

Cited By ~ 2

Author(s):

Te Li ◽

Junlian Gu ◽

Ou Yang ◽

Jianmeng Wang ◽

Yonggang Wang ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Reperfusion Injury ◽

Signaling Pathway ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Ischemia ◽

Mtor Signaling Pathway ◽

Exosomal Mirna

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Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7

Molecular and Cellular Biochemistry ◽

10.1007/s11010-019-03671-z ◽

2019 ◽

Vol 465 (1-2) ◽

pp. 103-114 ◽

Cited By ~ 7

Author(s):

Qi Chen ◽

Yu Liu ◽

Xueyan Ding ◽

Qinfeng Li ◽

Fuyu Qiu ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Myocardial Ischemia ◽

Western Blot ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

AbstractMicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1β, IL-6, and TNF-α in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.

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