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Published on: February 15, 2022
Matrix metalloproteinase-8 inhibitors mitigate sepsis-induced myocardial injury in rats
Xiaorui Zhou1, Jiakai Lu2, Dong Chen3
1Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Background:
Sepsis-induced myocardial injury (SIMI) is caused by a variety of mechanisms. The aim of the study is to investigate the effects of metalloproteinase-8 (MMP-8) on SIMI and its mechanisms in rats.
Methods:
Forty male Sprague Dawley rats were randomly divided into four groups: MMP-8 inhibitor (M8I), dexamethasone (DEX), sepsis, and sham groups. The sepsis model was established by cecal ligation and puncture (CLP). Rats in the M8I group immediately received an intraperitoneal injection of M8I (0.1 mg/kg) after CLP. Rats in the DEX group immediately received an intraperitoneal (IP) injection of DEX (2 mg/kg). Rats in the sepsis and sham groups received intraperitoneal injections of normal saline. Rats were sacrificed 12 hours after CLP. Paraffin sections were stained with hematoxylin and eosin to observe the myocardium. The myocardial ultrastructure was observed with transmission electron microscopy. MMP-8, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were detected by immunohistochemistry. The expression of MMP-8 was measured by Western blotting. TNF-α and IL-1β levels in serum and myocardial tissue were determined by enzyme-linked immunosorbent assay.
Results:
Compared with the sham group, the myocardium in the sepsis group was seriously injured. MMP-8, TNF-α and IL-1β expression was higher in the sepsis group than in the sham group. Treatment with M8I or DEX, however, attenuated sepsis induced histopathological changes in the heart, and was associated with significant reductions in serum and myocardial levels of TNF-α and IL-1β (P < 0.05). M8I significantly inhibited MMP-8 expression in myocardial tissue (P < 0.05). In addition, treatment with DEX was not associated with a change in myocardial levels of MMP-8 (P > 0.05).
Conclusion:
MMP-8 inhibitor attenuated myocardial injury in septic rats, which might be related to reduced expression of TNF-α and IL-1β.
Insights
Metalloproteinase-8 (MMP-8) inhibition reduced sepsis-induced myocardial injury in rats. This protective effect may stem from decreased levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).
Area of Science:
- Cardiology
- Pathophysiology
- Pharmacology
Background:
- Sepsis-induced myocardial injury (SIMI) involves complex mechanisms.
- Metalloproteinase-8 (MMP-8) is implicated in SIMI pathogenesis.
Purpose of the Study:
- To investigate the effects of MMP-8 on SIMI in a rat model.
- To elucidate the underlying mechanisms of MMP-8's role in SIMI.
Main Methods:
- A cecal ligation and puncture (CLP) model was used to induce sepsis in male Sprague Dawley rats.
- Rats were treated with an MMP-8 inhibitor (M8I) or dexamethasone (DEX).
- Myocardial injury, MMP-8, TNF-α, and IL-1β levels were assessed via histology, Western blotting, and ELISA.
Main Results:
- Sepsis led to significant myocardial injury, with elevated MMP-8, TNF-α, and IL-1β expression.
- M8I and DEX treatments attenuated cardiac histopathological damage and reduced serum/myocardial TNF-α and IL-1β levels.
- M8I significantly decreased myocardial MMP-8 expression, while DEX did not affect MMP-8 levels.
Conclusions:
- MMP-8 inhibition ameliorated myocardial injury in septic rats.
- Reduced expression of TNF-α and IL-1β may mediate the protective effects of MMP-8 inhibition in SIMI.
