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Objective To investigate the preventive effect of Toll-like receptor 4 (TLR4) agonist Lipopolysaccharides (LPS) on myocardial ischemia-reperfusion injury (MIRI) in rats and its mechanism. Methods Sixty rats were divided into the LPS intervention group (0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, all were small doses), verapamil intervention group, model group and sham operation group, with 15 rats in each group. At 7 days before the establishment of MIRI models, rats in the LPS intervention group were given intraperitoneal injection of 0.1 mg/kg, 0.5 mg/kg and 1 mg/kg LPS, rats in the verapamil intervention group were given intraperitoneal injection of 2.5% verapamil (2 mg/kg), rats in the sham operation group and model group were given intraperitoneal injection of equal volume normal saline. All were performed once a day. Then, except for the sham operation group, rats in the other groups underwent ischemia-reperfusion treatment. At 72 h after treatment, the cardiac function of rats in each group was detected by ultrasound, the myocardial histopathological changes were observed by hematoxylin-eosin (HE) staining, and the myocardial infarction size was observed by 2,3, 5-triphenyltetrazolium chloride (TTC) staining. The proteins of forkhead box proteinO3a (FoxO3a), phospho-forkhead box protein O3a (pFoxO3aS253), Beclin-1 and LC in rat myocardial tissues were detected by Western blotting. Results Compared with the sham operation group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) decreased (both P＜0.05), myocardial injury was more serious and the percentage of myocardial infarction area increased (both P＜0.05), the relative expression of pFoxO3aS253 protein in the myocardial tissues decreased (P＜0.05), and the relative expression levels of FoxO3a, Beclin-1, and LC proteins increased in the model group (all P＜0.05). Compared with the model group, LVEF and LVFS increased in the verapamil intervention group and LPS intervention group (both P＜0.05); there was no obvious improvement in cardiomyopathy in the 0.1 mg/kg and 0.5 mg/kg LPS intervention groups, and the degree of myocardial fibrosis edema, fracture, necrosis and inflammatory cell infiltration were reduced in the verapamil intervention group and 1 mg/kg LPS intervention group; the percentage of myocardial infarction area decreased (all P＜0.05), the relative expression level of pFoxO3aS253 protein increased (P＜0.05), and the relative expression levels of FoxO3a, Beclin-1 and LC proteins decreased in the verapamil intervention group and LPS intervention group (all P＜0.05). Conclusion Low-dose TLR4 agonist LPS can prevent MIRI in rats, and its mechanism may be related to promoting phosphorylation of FoxO3a and inhibiting activation of Beclin-1 and LC. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of human bone marrow-derived mesenchymal stem cells (MSC) and to clarify the underlying mechanisms. The expression of TLR2 and TLR4 on MSC was detected by flow cytometry. The effects of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on MSC migration and adhesion ability were evaluated with chemotaxis and adhesion test. The results indicated that expressive levels of TLR2 and TLR4 on surface of human bone marrow MSC were (24.5 ± 3.2)% and (91.3 ± 5.2)% respectively. Compared with the control group, the migration activity of MSC toward SDF-1 was decreased significantly in PAM3CSK4 group, while the adhesion activity of MSC was promoted by PAM3CSK4 exposure. However, both the migration activity toward SDF-1 and the adhesion activity of MSC were not changed significantly in LPS-treated group. Further, it was found that PAM3CSK4 did not affect the expressive level of CXCR4 on MSC, however, it could inhibit the spontaneous migration of MSC in dose dependent manner. It is concluded that activation of TLR2 can decrease the migration ability of MSC, which may associate with the decreased spontaneous migration ability and the increased adhesion activity of MSC.

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p < 0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.