异荭草素对2型糖尿病大血管病变小鼠主动脉的保护作用及机制研究

To Investigate the Protective Effect and Mechanism of Isoorientin on Aortic in T2DM Macrovascular Disease Mice

摘要: 目的：探讨异荭草素对T2DM大血管病变小鼠主动脉的保护作用及机制。方法：C57BL/6J雄性小鼠随机分为正常对照组(NC组)和实验组。以高脂饲料(含量60%)喂养和链脲佐菌素(STZ)腹腔注射制备2型糖尿病大血管病变模型。将成模的T2DM大血管病变小鼠随机分成模型组和异荭草素治疗组。异荭草素治疗组再分低、中、高剂量，分别按照10、20、40 mg⋅kg⁻¹剂量腹腔注射给药。正常组、模型组给予腹腔注射等量溶剂0.5%羧甲基纤维素钠。实验期间观察动物一般状况并测血糖。8周后处死小鼠取胸主动脉标本。光镜下观察其病理结构，ELisa检测血管组织中AGEs水平，RT-qPCR检测RAGE、IL-6、P65、TNF-α、Vcam-1mRNA的表达水平。结果：镜下观察，与模型对照组相比，异荭草素各治疗组内膜增厚、弹力纤维断裂、泡沫细胞聚集明显减轻。与模型对照组相比，异荭草素干预后随机血糖显著下降(F = 82.20, P < 0.001)，血管中AGEs浓度显著降低(F = 60.180，P < 0.001)，异荭草素各治疗组血管中RAGE、IL-6、NF-κB p65、TNF-α、Vcam-1等因子的表达水平显著下降(F = 68.05~1692, P < 0.01)。结论：异荭草素可通过抑制炎症反应，改善糖尿病大血管病变。

Abstract: Objective: To investigate the protective effect and mechanism of isoorientin on macrovascular dis-eases in T2DM mice. Methods: Male C57BL/6J mice were randomly divided into normal control group (NC group) and experimental group. Type 2 diabetic macroangiopathopathy model was es-tablished by feeding high-fat diet (60%) and intrabitoneal injection of streptozotocin (STZ). Model T2DM macrovascular disease mice were randomly divided into model group and isoorientin treat-ment group. Isoorientin treatment group was divided into low, medium and high doses by intraper-itoneal injection of 10, 20 and 40 mg⋅kg⁻¹ respectively. Normal group and model group were intra-peritoneally injected with 0.5% sodium carboxymethyl cellulose. During the experiment, the gen-eral condition of animals was observed and blood glucose was measured. After 8 weeks, the mice were sacrificed for thoracic aorta specimens. The pathological structure was observed under light microscope, AGEs levels in vascular tissues were detected by ELisa, and mRNA expression levels of RAGE, IL-6, P65, TNF-α and VCAM-1 were detected by RT-qPCR. Results: Compared with the model control group, the endometrial thickening, elastic fiber fracture and foam cell aggregation in isoorientin treatment groups were significantly reduced. Results: Compared with the model control group, the isoorientin treatment groups random blood glucose decreased significantly (F = 82.20, P < 0.001) and the concentration of AGEs in blood vessels decreased significantly (F = 60.18, P < 0.001). Compared with the model congtrol group, the isoorientin treatment groups also had signifi-cantin decreases in the expression levels of RAGE, IL-6, NF-κB p65, TNF-α, and Vcam-1 in blood ves-sels (F = 68.05~1692, P < 0.01). Conclusion: Isoorientin can improve diabetic macroangiopathy by inhibiting the inflammatory response.