Mokgalaboni Kabelo, Dludla Phiwayinkosi V, Mkandla Zibusiso, Mutize Tinashe, Nyambuya Tawanda Maurice, Mxinwa Vuyolwethu, Nkambule Bongani B
School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa.
Biomedical Research and Innovation Platform (BRIP), The South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa.
Metabol Open. 2020 Aug 1;7:100047. doi: 10.1016/j.metop.2020.100047. eCollection 2020 Sep.
To assess the levels of glycoprotein GPIV (CD36) expression on peripheral blood monocyte subsets, in a mouse model of glucose intolerance. Moreover, to determine the effect of; low-dose aspirin (LDA) alone, LDA combined with metformin, or clopidogrel alone, on the expression of CD36 on subsets of circulating monocytes.
The study consisted of two experimental phases. In experiment one, the mice (n = 14) were randomised to receive a low-fat diet (LFD) or a high-fat diet (HFD) for eight weeks. Whereas the secondary phase of the experiment, comprised of twenty-four HFD-fed mice treated with LDA alone (3 mg/kg), or in combination with metformin (150 mg/kg), or clopidogrel alone (10 mg/kg) for six weeks. The surface expression of CD36 on monocytes was measured using flow cytometry.
The levels of CD36 expression on monocytes were upregulated in the HFD-fed compared to LFD-fed group (p < 0.05). In addition, HFD group showed; no significant changes in body weight (p = 0.3848), however, blood glucose (p = 0.0002) and insulin (p = 0.0360) levels were markedly increased following HFD-feeding. Interestingly, all treatments reduced the expression of CD36 on monocytes, decreased fasting blood glucose levels (p = 0.0024) and increased circulating monocyte levels (p = 0.0217) when compared to the untreated HFD group. Moreover, treatment with LDA alone increased basophils levels (p = 0.0272), while when combined with metformin showed an improved effect in enhancing eosinophil levels (p = 0.0302).
HFD-feeding increased the expression of CD36 on monocyte subsets. LDA as a monotherapy or combined with metformin was as effective as clopidogrel monotherapy, in downregulating the expression of CD36 on monocyte subsets. These treatments may be of relevance in preventing cardiovascular complications associated with impaired glucose tolerance.
在葡萄糖不耐受小鼠模型中评估外周血单核细胞亚群上糖蛋白GPIV(CD36)的表达水平。此外,确定单独使用低剂量阿司匹林(LDA)、LDA联合二甲双胍或单独使用氯吡格雷对循环单核细胞亚群上CD36表达的影响。
该研究包括两个实验阶段。在实验一中,将小鼠(n = 14)随机分为接受低脂饮食(LFD)或高脂饮食(HFD)八周。而实验的第二阶段,由24只接受HFD喂养的小鼠组成,分别单独用LDA(3 mg/kg)、或与二甲双胍(150 mg/kg)联合、或单独用氯吡格雷(10 mg/kg)治疗六周。使用流式细胞术测量单核细胞上CD36的表面表达。
与LFD喂养组相比,HFD喂养组单核细胞上CD36的表达水平上调(p < 0.05)。此外,HFD组显示;体重无显著变化(p = 0.3848),然而,喂食HFD后血糖(p = 0.0002)和胰岛素(p = 0.0360)水平显著升高。有趣的是,与未治疗的HFD组相比,所有治疗均降低了单核细胞上CD36的表达,降低了空腹血糖水平(p = 0.0024)并增加了循环单核细胞水平(p = 0.0217)。此外,单独使用LDA治疗可增加嗜碱性粒细胞水平(p = 0.0272),而与二甲双胍联合使用时在提高嗜酸性粒细胞水平方面显示出更好的效果(p = 0.0302)。
喂食HFD会增加单核细胞亚群上CD36的表达。LDA作为单一疗法或与二甲双胍联合使用在下调单核细胞亚群上CD36的表达方面与氯吡格雷单一疗法同样有效。这些治疗可能与预防与葡萄糖耐量受损相关的心血管并发症有关。