Correlation between Fc γ RIIIA and Aortic Atherosclerotic Plaque Destabilization in ApoE Knockout Mice and Intervention Effects of Effective Components of Chuanxiong Rhizome and Red Peony Root
Correlation between Fc γ RIIIA and Aortic Atherosclerotic Plaque Destabilization in ApoE Knockout Mice and Intervention Effects of Effective Components of Chuanxiong Rhizome and Red Peony Root
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DOI：
10.1007/s11655-011-0726-y
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发表时间：
2011-05-01
影响因子：
2.9
通讯作者：
Chen Ke-ji
中科院分区：
文献类型：
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作者：
Huang Ye;Yin Hui-jun;Chen Ke-ji
目标：探讨Fc γ RIIIA（CD 16 A）与apoE基因敲除（apoE KO）小鼠主动脉粥样硬化斑块不稳定的相关性及白术、赤芍有效成分的干预作用。方法：8只8周龄雄性C57 BL/6 J小鼠作为对照组。将40只8周龄雄性apoE基因敲除小鼠随机分为模型组、apoE基因敲除+腹腔注射免疫球蛋白组（IVIG）、apoE基因敲除+辛伐他汀组（Sm）、apoE基因敲除+雄芍胶囊高剂量组（XSCH）、apoE基因敲除+雄芍胶囊低剂量组（XSCL），每组8只。对照组的小鼠被喂食正常饮食，其他小鼠被喂食高脂肪饮食。10周后，采用流式细胞仪检测单核细胞CD 16表达，逆转录-聚合酶链反应检测主动脉基质金属蛋白酶-9（MMP-9）mRNA表达，酶联免疫吸附法检测血清肿瘤坏死因子（TNF）-α水平。结果如下：与对照组比较，模型组大鼠主动脉MMP-9 mRNA表达、单核细胞CD 16表达及血清TNF-α水平均明显升高（P < 0.01）。apoE基因敲除小鼠腹腔注射免疫球蛋白5天后，单核细胞CD 16表达、主动脉MMP-9 mRNA表达和血清TNF-α水平均显著低于高脂饮食10周后（P < 0.01或0.05）。Sm组、XSCH组、XSCL组上述指标均有不同程度的降低。其中XSCH组主动脉MMP-9 mRNA表达低于Sm组（P < 0.05），单核细胞CD 16表达和血清TNF-α水平与Sm组比较差异无统计学意义（P > 0.05）。相关分析显示IVIG组、XSCH组、XSCL组主动脉MMP-9 mRNA表达和血清TNF-α水平与单核细胞CD 16表达呈正相关。结论：Fc γ RIIIA介导冠心病血瘀证的全身炎症反应。XSC通过抑制炎症反应稳定动脉粥样硬化斑块，其作用靶点与Fc γ RIIIA相关。
Objective: To explore the correlation between Fc gamma RIIIA (CD16A) and aortic atherosclerotic plaque destabilization in apoE knockout (apoE KO) mice and the intervention effects of effective components of Chuanxiong Rhizome and Red Peony Root. Methods: Eight 8-week-old male C57BL/6J mice were selected as the control group. Forty 8-week-old male apoE KO mice were randomly divided into the model group, apoE KO + intraperitoneal injection immunoglobulin group (IVIG), apoE KO + simvastatin group (Sm), apoE KO + high dosage of Xiongshao Capsule (XSC, (sic)) group (XSCH), and apoE KO + low dosage of XSC group (XSCL), 8 mice in each group. Mice in the control group were put on a normal diet, and others were fed with a high-fat diet. After 10-week different interventions, monocyte CD16 expression was detected by flow cytometry, aortic matrix metalloproteinase-9 (MMP-9) mRNA expression was detected using reverse transcription-polymerase chain reaction, and serum tumor necrosis factor (TNF)-alpha level was detected using enzyme-linked immunosorbent assay. Results: Compared with the control group, monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-alpha level in the model group increased obviously (P < 0.01). Injections of apoE KO mice with intraperitoneal immunoglobulin during a 5-day period significantly reduced the monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-alpha level (P < 0.01 or 0.05) over a 10-week period of high-fat diet. Indices above in the Sm group, XSCH group, and XSCL group decreased in a different degree. Of them, the aortic MMP-9 mRNA expression in XSCH group was lower than that in Sm group (P < 0.05) and the monocyte CD16 expression and serum TNF-alpha level showed no significant difference between XSCH group and Sm group (P > 0.05). Correlation analyses suggested positive correlation between monocyte CD16 expression and aortic MMP-9 mRNA expression or serum TNF-alpha level in IVIG group, XSCH group, and XSCL group. Conclusions: Fc gamma RIIIA mediates systemic inflammation in the progression of coronary heart disease with blood stasis syndrome. XSC could stabilize atherosclerotic plaque by suppressing inflammation and its target was relative with Fc gamma RIIIA.