Matrix metalloproteinase-8 inhibitors mitigate sepsis-induced myocardial injury in rats.
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).


CONCLUSIONS
MMP-8 inhibitor attenuated myocardial injury in septic rats, which might be related to reduced expression of TNF-α and IL-1β.
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Xiaorui
X
Zhou
Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
Jiakai
J
Lu
Department of Pathology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
Dong
D
Chen
Department of Pathology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
Wei
W
Wang
Medical Experiment & Testing Center, Capital Medical University, Beijing 100069, China.
Qing
Q
Cai
Department of Stroke, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
Tongxun
T
Li
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Email: jinglanzhang2006@aliyun.com.
Jinglan
J
Zhang
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006331:Heart Diseases / Q000188:drug therapy* / Q000209:etiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D020784:Matrix Metalloproteinase 8