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| Effect of adipose-derived mesenchymal stem cell exosomes on myocardial ischemia / reperfusion injury in rats and the effect of Wnt3a/β-catenin signaling pathway#br# |
| CHEN Xiaojia GUO Ziao GUO Jinhua LI Linke ZHANG Jiankai YANG Chun CUI Xiaojun |
| Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Medical University, Guangdong Province, Dongguan 523808, China |
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Abstract Objective To study the protective effect of adipose-derived mesenchymal stem cell exosomes (ADMSC-exs) on myocardial ischemia / reperfusion (I/R) injury in rats and the influence on the Wnt3a/β-catenin signaling pathway. Methods A total of 40 adult rats were randomly divided into four groups: S group (sham operation group), only thoracotomy without ligation of the coronary artery left anterior descending (LAD); I/R group, reperfusion after ligation of LAD 30 min; in the Ex group, LAD was ligated for 30 minutes and then reperfused, and ADMSC-exs was injected into the tail vein within five minutes of reperfusion; in the Ex+X group, LAD was ligated for 30 minutes and then reperfused, and ADMSC-exs and XAV939 were injected from the tail vein within five minutes of reperfusion. Ten rats in each group. The levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI), and myocardial cell apoptosis index (AI) in each group of myocardial ischemic area were detected by TUNEL method; Western blot was used to detect B lymphoma-2 gene (Bcl-2), Bcl-2 related X protein (Bax), caspase-3, Wnt3a, and β-catenin. Results The levels of LDH, CK-MB and cTnI in the I/R group were higher than those in the S group, and the differences were statistically significant (P ＜ 0.05). The levels of myocardial enzymes in the Ex group was lower than those in the I/R group, and the differences were statistically significant (P ＜ 0.05). When the Wnt3a/β-catenin pathway inhibitor XAV939 was injected into the tail vein, the levels of myocardial enzymes in the Ex+X group were higher than those in the Ex group, and the differences were statistically significant (P ＜ 0.05); compared with the I/R group, there was no statistical difference between two groups (P ＞ 0.05). The AI of S group was lower than that of I/R group, and the difference was statistically significant (P ＜ 0.05). After ADMSC-exs treatment, AI in Ex group was lower than that in I/R group, and the difference was statistically significant (P ＜ 0.05). The Bcl2/Bax ratio of I/R group lower higher than that of S group, and the difference was statistically significant (P ＜ 0.05). The Bcl2/Bax ratio of Ex group was higher than that of I/R group, and the difference was statistically significant (P ＜ 0.05). The level of caspase-3 in Ex group was lower than that in I/R group, and the difference was statistically significant (P ＜ 0.05). The level of caspase-3 in Ex+X group was significantly higher than that in Ex group, and the difference was statistically significant (P ＜ 0.05). The levels of Bcl2/Bax, Wnt3a, and β-catenin in the I/R group were lower than those in the S group, while the caspase-3 level was higher than that in the S group, and the differences were statistically significant (P ＜ 0.05). The levels of Bcl2/Bax, Wnt3a and β-catenin in the Ex group were higher than those in the I/R group, while the level of caspase-3 was lower than that in the S group, and the differences were statistically significant (P ＜ 0.05). The levels of Bcl2/Bax, Wnt3a, and β-catenin in the Ex+X group were lower than those in the S group, while the caspase-3 level was higher than that in the Ex group, and the differences were statistically significant (P ＜ 0.05). Conclusion ADMSC-exs can protect cardiomyocytes after I/R by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax and caspase-3. Its mechanism may be related to the Wnt3a/β-catenin signaling pathway.
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