基质金属蛋白酶-8抑制剂可减轻大鼠脓毒症诱导的心肌损伤。

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

作者信息

Zhou Xiaorui, Lu Jiakai, Chen Dong, Wang Wei, Cai Qing, Li Tongxun, Zhang Jinglan

机构信息

Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.

Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.

出版信息

Chin Med J (Engl). 2014;127(8):1530-5.

PMID:24762601

Abstract

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.

摘要

背景

脓毒症诱导的心肌损伤（SIMI）由多种机制引起。本研究旨在探讨金属蛋白酶-8（MMP-8）对大鼠SIMI的影响及其机制。

方法

将40只雄性Sprague Dawley大鼠随机分为四组：MMP-8抑制剂（M8I）组、地塞米松（DEX）组、脓毒症组和假手术组。采用盲肠结扎穿孔术（CLP）建立脓毒症模型。M8I组大鼠在CLP后立即腹腔注射M8I（0.1 mg/kg）。DEX组大鼠立即腹腔注射DEX（2 mg/kg）。脓毒症组和假手术组大鼠腹腔注射生理盐水。CLP后12小时处死大鼠。取石蜡切片进行苏木精-伊红染色以观察心肌。用透射电子显微镜观察心肌超微结构。通过免疫组织化学检测MMP-8、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）。用蛋白质免疫印迹法检测MMP-8的表达。采用酶联免疫吸附测定法测定血清和心肌组织中TNF-α和IL-1β水平。

结果

与假手术组相比，脓毒症组心肌损伤严重。脓毒症组MMP-8、TNF-α和IL-1β表达高于假手术组。然而，M8I或DEX治疗减轻了脓毒症诱导的心脏组织病理学变化，并与血清和心肌中TNF-α和IL-1β水平显著降低相关（P < 0.05）。M8I显著抑制心肌组织中MMP-8的表达（P < 0.05）。此外，DEX治疗与心肌MMP-8水平变化无关（P > 0.05）。