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. 2018 May 15;38(3):BSR20170939.
doi: 10.1042/BSR20170939. Print 2018 May 15.

Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion

Chengfu Song  1 , Xiangdong Zhao  2
Affiliations

Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion

Chengfu Song et al. Biosci Rep. .

Abstract

In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO.

Keywords: Uric acid; middle cerebral artery occlusion; oxidative stress; vascular endothelial cell apoptosis.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Increased UA concentration and enhanced oxidative stress in AS patients
(A) The concentrations of UA in Non-AS, AS-mild, AS-moderate, and AS-severe groups and the correlation between UA concentration and AS severity. (B) The concentrations of NO in Non-AS, AS-mild, AS-moderate, and AS-severe groups. (C) The activities of eNOS in Non-AS, AS-mild, AS-moderate, and AS-severe groups. (D) The concentrations of 8-OHdG in Non-AS, AS-mild, AS-moderate, and AS-severe groups. (E) The activities of GSH-Px in Non-AS, AS-mild, AS-moderate, and AS-severe groups. (F) The activities of SOD in Non-AS, AS-mild, AS-moderate, and AS-severe groups. According to the CT examination results, CI patients were divided into two groups: AS and Non-AS group (n = 43 in each group). According to NASCCET classification, vascular atherosclerotic stenosis can be classified as: <29% for mild stenosis (AS-mild, n=15), 30–69% for moderate stenosis (AS-moderate, n=15), >90% for severe stenosis (AS-severe, n=13); *P<0.05 and **P<0.01 compared with Non-AS group.
Figure 2
Figure 2. UA exacerbates morphological damage in rats with MCAO
UA exacerbated morphological damage in rats with MCAO in a dose-dependent manner. Aorta was separated and was fixed in formalin, then was embedded in paraffin, and sliced into 5-μm-thick sections. Sections were stained with HE and visualized under a microscope (Leica DM 2500). Rats were received an intragastric administration of UA at 50, 100, 150, and 200 mg/kg body weight twice one day for 12 weeks consecutively (n = 11 in each group). Rats treated with normal saline were used as the control group (MCAO + saline). a and b in Sham group indicates internal elastic membrane and smooth muscle cell. The arrow in MCAO + UA (200 mg/kg) and MCAO + UA (400 mg/kg) groups indicate foam cells.
Figure 3
Figure 3. UA promotes oxidative stress in rats with MCAO
(A) The concentration of UA in each group. (B) The activity of eNOS in each group. (C) The concentration of 8-OHdG in each group. (D) The activity of GSH-Px in each group. (E) The activity of SOD in each group. Rats were received an intragastric administration of UA at 50, 100, 150, and 200 mg/kg body weight twice one day for 12 weeks consecutively (n = 11 in each group). Rats treated with normal saline were used as the control group (MCAO + saline). **P<0.01 compared with Sham group. #P<0.5 and ##P<0.01 compared with MCAO + saline group.
Figure 4
Figure 4. UA enhances vascular endothelial cell apoptosis in rats with MCAO
(A) The apoptotic cell in each group were visualized under an episcopic-fluorescence microscopy. (B) Statistical analysis of the apoptotic cell rate in each group. Aortic endothelial cells were isolated from rats as previously described [17]. **P<0.01 compared with Sham group. #P<0.5 and ##P<0.01 compared with MCAO + saline group. An in situ apoptotic cell death detection kit TMR red (Roche Applied Science, Indianapolis, IN) based on a TUNEL assay was used to detect apoptotic cells. The apoptotic rate (%) is expressed as the number of apoptotic cells over the total number of cells. **P<0.01 compared with Sham group. #P<0.5 and ##P<0.01 compared with MCAO + saline group. Red indicates the apoptotic cells and blue indicates nucleus.
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References

    1. Zhang B., Yang N., Lin S.P. and Zhang F. (2016) Suitable concentrations of uric acid can reduce cell death in models of OGD and cerebral ischemia-reperfusion injury. Cell. Mol. Neurobiol. 1–9 - PubMed
    1. Fernandez-Ortiz A., Badimon J.J. and Fuster V. (1999) Pathogenesis of Atherosclerosis, Springer, US
    1. Dahl A., Lund C. and Russell D. (2007) Atherosclerosis and cerebral infarction. Tidsskrift for Den Norske Lægeforening Tidsskrift for Praktisk Medicin Ny Række 127, 892 10.1016/S1001-9294(10)60017-X - DOI - PubMed
    1. Li G.W., Zheng G.Y., Li J.G. and Sun X.D. (2010) Relationship between carotid atherosclerosis and cerebral infarction. Chin. Med. Sci. J. 25, 32. - PubMed
    1. Amarenco P., Lavallée P.C., Labreuche J., Ducrocq G., Juliard J.M., Feldman L. et al. (2011) Prevalence of coronary atherosclerosis in patients with cerebral infarction. Stroke 42, 22 10.1161/STROKEAHA.110.584086 - DOI - PubMed

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