Role of interleukin-6 in brain tissues in cognitive impairment after myocardial infarction in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of interleukin-6 (IL-6) in brain tissues in cognitive impairment after myocardial infarction in mice.Methods:Forty SPF healthy male C57/BL6J mice and 40 IL-6Rα flox/flox: CAMKⅡ Cre (IL-6Rα NKO) mice, aged 9 months, weighing 34-39 g, were divided into 2 groups ( n=20 each) using a random number table method: sham operation group (Sham group, IL-6Rα NKO-Sham group) and myocardial infarction group (MI group, IL-6Rα NKO-MI group). Myocardial infarction model was developed by ligating the left anterior descending coronary artery in anesthetized animals. The same surgery was performed without ligation of blood vessels in Sham group. At 28 days after preparing the myocardial infarction model, cardiac function was assessed by cardiac doppler echocardiography, and cognitive function was assessed using the Barnes maze test. Then mice were sacrificed, and brain tissues were collected for determination of the expression of IL-6, c-Fos, ionized calcium-binding adaptor molecule 1 (Iba-1, a marker protein for microglia activation) and glial fibrillary acidic protein (GFAP) (by immunofluorescence staining) in the hippocampal CA3 region. The ultrastructure of synapses in the hippocampi was examined with a transmission electron microscope to record the number of synapses and thickness of postsynaptic density (PSD). Results:Compared with sham operation groups, the ejection fraction and shortening rate of short axis were significantly decreased, and the left ventricular end-systolic diameter was increased in myocardial infarction groups ( P<0.05). Compared with Sham group, the latency to reach the target hole was significantly prolonged in the Barnes maze test, the expression of IL-6, c-Fos, GFAP and Iba1 was up-regulated in the hippocampal CA3 region, and the number of synapses and thickness of PSD were decreased in MI group ( P<0.05). Compared with IL-6Rα NKO-Sham group, the number of synapses in hippocampal neurons was significantly decreased ( P<0.05), and no significant change was found in the other parameters in IL-6Rα NKO-MI group ( P>0.05). Compared with MI group, the latency to reach the target hole was significantly shortened in the Barnes maze test, the expression of IL-6, c-Fos, GFAP and Iba1 was down-regulated in the hippocampal CA3 region, and the number of synapses and thickness of PSD were increased in IL-6Rα NKO-MI group ( P<0.05). Conclusions:The mechanism underlying cognitive impairment after myocardial infarction may be related to hippocampal synaptic damage caused by IL-6-mediated neuroinflammatory responses in mice.