Protective effect and mechanism of γ-secretase inhibitor on myocardial injury in sepsis rats
AJTR Copyright © 2023..
OBJECTIVE: This study aimed to investigate the mechanism of γ-secretase inhibitor (GSI) in myocardial repair in septic rats.
METHODS: Thirty-six healthy male Wistar rats were randomly and equally divided into control groups, model group and intervention group. The model group and the intervention group were treated with ligation of cecum and perforation to build sepsis model, and the intervention group received intraperitoneal injection of GSI II (DAPT). Serum levels of Troponin T (cTnT), creatine kinase isoenzyme (CK-MB) and interleukin-17 were measured by ELISA. The Th17 cell percentage in peripheral blood mononuclear cells in CD4+ cells was determined by flow cytometry, and myocardial tissue cells in each group were measured by TUNEL. The mRNA of RORγt was measured by real-time quantitative PCR, and the protein expressions of Notch1, Hes1 and HIF-α in myocardial tissue were measured by Western blot.
RESULTS: The cTnT, CK-MB, Th17 and Th17/CD4+ levels in the model group and the intervention group were remarkably higher than those in the control group (P<0.05), while those in the intervention group were remarkably lower than those in the model group (P<0.05). Myocardial apoptosis rate, myocardial RORγt mRNA and protein expressions of Notch1, Hes1 and HIF-α in the model group and the intervention group were obviously higher than those in control group (P<0.05), and those in the intervention group were obvious lower than those in the model group (P<0.05).
CONCLUSION: γ secretase inhibitors have clearly protective effects on cardiomyocytes, and the mechanism may be associated with Notch blocking and RORγt expression, which inhibit immune damage induced by abnormal activation of Th17.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
American journal of translational research - 15(2023), 2 vom: 17., Seite 1017-1025 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fang, Jingyun [VerfasserIn] |
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| Themen: |
γ secretase inhibitor |
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| Anmerkungen: |
Date Revised 15.03.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354213326 |
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| 100 | 1 | |a Fang, Jingyun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Protective effect and mechanism of γ-secretase inhibitor on myocardial injury in sepsis rats |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Revised 15.03.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a AJTR Copyright © 2023. | ||
| 520 | |a OBJECTIVE: This study aimed to investigate the mechanism of γ-secretase inhibitor (GSI) in myocardial repair in septic rats | ||
| 520 | |a METHODS: Thirty-six healthy male Wistar rats were randomly and equally divided into control groups, model group and intervention group. The model group and the intervention group were treated with ligation of cecum and perforation to build sepsis model, and the intervention group received intraperitoneal injection of GSI II (DAPT). Serum levels of Troponin T (cTnT), creatine kinase isoenzyme (CK-MB) and interleukin-17 were measured by ELISA. The Th17 cell percentage in peripheral blood mononuclear cells in CD4+ cells was determined by flow cytometry, and myocardial tissue cells in each group were measured by TUNEL. The mRNA of RORγt was measured by real-time quantitative PCR, and the protein expressions of Notch1, Hes1 and HIF-α in myocardial tissue were measured by Western blot | ||
| 520 | |a RESULTS: The cTnT, CK-MB, Th17 and Th17/CD4+ levels in the model group and the intervention group were remarkably higher than those in the control group (P<0.05), while those in the intervention group were remarkably lower than those in the model group (P<0.05). Myocardial apoptosis rate, myocardial RORγt mRNA and protein expressions of Notch1, Hes1 and HIF-α in the model group and the intervention group were obviously higher than those in control group (P<0.05), and those in the intervention group were obvious lower than those in the model group (P<0.05) | ||
| 520 | |a CONCLUSION: γ secretase inhibitors have clearly protective effects on cardiomyocytes, and the mechanism may be associated with Notch blocking and RORγt expression, which inhibit immune damage induced by abnormal activation of Th17 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a mechanism | |
| 650 | 4 | |a myocardial injury | |
| 650 | 4 | |a myocardial protection | |
| 650 | 4 | |a sepsis | |
| 650 | 4 | |a γ secretase inhibitor | |
| 700 | 1 | |a Zhou, Yuming |e verfasserin |4 aut | |
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