动脉粥样硬化是心血管疾病的重要病因之一。近年来,已经确定解整合素和金属蛋白酶(ADAM)10和ADAM17是炎症的重要调节剂。我们的研究调查了用选择性抑制剂和蜂胶抑制这些酶对动脉粥样硬化的影响。在我们的研究中,C57BL/6J小鼠(n=16)用于对照组和假手术组。相比之下,ApoE-/-小鼠(n=48)用于病例,蜂胶水提取物(WEP),蜂胶乙醇提取物(EEP),GW280264X(GW-合成抑制剂),和溶剂(DMSO和乙醇)基团。对照组饲喂对照饮食,和所有其他组喂养高胆固醇饮食16周。WEP(400mg/kg/天),EEP(200mg/kg/天),和GW(100µg/kg/天)在最后四周腹膜内给药。动物被处死,和血,肝脏,主动脉弓,并收集主动脉根部组织。在血清中,总胆固醇(TC),甘油三酯(TG),通过酶比色法测量葡萄糖(Glu),而白细胞介素-1β(IL-1β),对氧磷酶-1(PON-1),采用ELISA法测定脂蛋白相关磷脂酶A2(Lp-PLA2)。肿瘤坏死因子-α(TNF-α),干扰素-γ(IFN-γ),髓过氧化物酶(MPO),白细胞介素-6(IL-6),白细胞介素-10(IL-10),用ELISA法测定主动脉弓中白细胞介素-12(IL-12)的水平,用荧光法测定ADAM10/17的活性。此外,对主动脉根部和肝组织进行组织病理学和免疫组织化学检查(ADAM10和sortilin一级抗体)。在WEP中,EEP,和GW组与病例组相比,TC,TG,TNF-α,IL-1β,IL-6,IL-12,PLA2,MPO,ADAM10/17活动,斑块负荷,脂质积累,ADAM10和sortilin水平下降,而IL-10和PON-1水平升高(p<0.003)。我们的研究结果表明,蜂胶可以通过抑制ADAM10/17有效降低动脉粥样硬化相关的炎症和血脂异常。
Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and
propolis on atherosclerosis. In our study, C57BL/6J mice (n = 16) were used in the control and sham groups. In contrast, ApoE-/- mice (n = 48) were used in the case, water extract of
propolis (WEP), ethanolic extract of
propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1β, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased (p < 0.003). Our study results show that
propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.