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目的:探讨重组融合蛋白TAP-SSL5对Apo E基因敲除(Apo E~(-/-))小鼠动脉血管粥样硬化斑块形成的影响。方法:21只12周龄Apo E~(-/-)小鼠随机分为3组,每日分别给予TAP-SSL5(3 mg/kg)、SSL5(2 mg/kg)及同等剂量的PBS,高脂饮食饲养12周后,石蜡切片观察主动脉根部粥样硬化斑块形成情况,并应用油红O染色法观察大体动脉标本斑块情况;最后应用小鼠细胞炎症因子芯片检测TAP-SSL5对40种炎症因子在动脉组织内的表达情况。结果:高脂饲养12周后,TAP-SSL5组小鼠体重增长明显低于单纯喂食高脂饮食而不进行药物干预组,血清胆固醇(Tch)水平明显低于对照组,而甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)及高密度脂蛋白胆固醇(HDL)水平无明显变化。TAP-SSL5可以减轻Apo E~(-/-)小鼠动脉血管粥样硬化斑块形成(P<0.05)。炎症因子芯片表达分析显示,与对照组相比较,TAP-SSL5组GM-CSF、IL-3、IL-10、IL-1β、IL-12p40p70、IL-9、IL-12p70、KC、Lymphotactin、Leptin、MCP-1、MIG、MCSF、MIP-1α、s TNF RI、RANTES和s TNF RII共17种细胞因子下调明显。结论:重组融合蛋白TAP-SSL5能够在一定程度上抑制Apo E~(-/-)小鼠动脉粥样硬化斑块的形成,其机制与其抗炎、抗凝及抗血小板特性有关,其对细胞因子表达调控的影响有待深入研究。
Objective: To investigate the effect of recombinant fusion protein TAP-SSL5 on the formation of atherosclerotic plaque in ApoE-knockout (Apo E ~ (- / -)) mice. METHODS: Twenty-one 12-week-old Apo E ~ (- / -) mice were randomly divided into three groups. TAP-SSL5 (3 mg / kg), SSL5 (2 mg / After 12 weeks of feeding with high-fat diet, paraffin sections were used to observe the formation of aortic root atherosclerotic plaque. Oil red O staining was used to observe the plaque in the common arterial samples. Finally, TAP-SSL5 40 kinds of inflammatory factors in the arterial tissue expression. Results: After 12 weeks of high-fat diet, the body weight of mice in TAP-SSL5 group was significantly lower than that in high-fat diet group without drug intervention. The level of serum cholesterol (Tch) was significantly lower than that of the control group. Triglyceride ), Low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL) levels did not change significantly. TAP-SSL5 attenuated the formation of atherosclerotic plaque in ApoE ~ (- / -) mice (P <0.05). The expression of inflammatory cytokines showed that the expression of GM-CSF, IL-3, IL-10, IL-1β, IL-12p40p70, IL-9, IL-12p70, KC, Lymphotactin and Leptin in TAP- 17 cytokines including MCP-1, MIG, MCSF, MIP-1α, s TNF RI, RANTES and s TNFRII were significantly down-regulated. Conclusion: The recombinant fusion protein TAP-SSL5 can inhibit the formation of atherosclerotic plaque in Apo E ~ (- / -) mice to a certain extent. Its mechanism is related to its anti-inflammatory, anticoagulant and antiplatelet properties. The impact of regulation of factor expression needs further study.