Endothelial Dysfunction and Inflammation Precedes Elevations in Blood Pressure Induced by a High-Fat Diet

Abstract Background: Obesity leads to a chronic inflammatory state, endothelial dysfunction and hypertension. Objective: To establish the time-course of events regarding inflammatory markers, endothelial dysfunction, systolic blood pressure (SBP) in obesity in only one experimental model. Methods: We fed male Wistar rats (eight-week age) with a standard diet (Control - CT, n = 35), or palatable high-fat diet (HFD, n = 35) for 24 weeks. Every six weeks, 7 animals from each group were randomly selected for euthanasia. SBP and serum levels of interleukin-6, tumor necrosis factor-α, C-reactive protein, adiponectin and nitric oxide were determined. Endothelial and vascular smooth muscle functions were determined in dissected aorta and lipid peroxidation was measured. Statistical significance was set at p < 0.05. Results: Levels of pro-inflammatory cytokines began to increase after six weeks of a high-fat diet, while those of the anti-inflammatory cytokine adiponectin decreased. Interestingly, the endothelial function and serum nitric oxide began to decrease after six weeks in HFD group. The SBP and lipid peroxidation began to increase at 12 weeks in HFD group. In addition, we showed that total visceral fat mass was negatively correlated with endothelial function and positively correlated with SBP. Conclusion: Our results show the time-course of deleterious effects and their correlation with obesity.

研究背景：肥胖可引发慢性炎症状态、内皮功能障碍与高血压。
研究目的：仅通过单一实验模型，明确肥胖相关炎症标志物、内皮功能障碍及收缩压（systolic blood pressure, SBP）的动态变化过程。
研究方法：将8周龄雄性Wistar大鼠随机分为两组，分别饲喂标准饲料（对照组（Control, CT），n=35）与高脂适口饲料（palatable high-fat diet, HFD，n=35），造模周期为24周。每6周从每组随机选取7只大鼠实施安乐死。检测各组大鼠的收缩压、血清白细胞介素-6、肿瘤坏死因子-α、C反应蛋白、脂联素与一氧化氮水平；分离主动脉检测内皮功能与血管平滑肌功能，并测定脂质过氧化水平。本研究设定检验水准为p<0.05。
研究结果：高脂饲料组大鼠在造模6周后，促炎细胞因子水平即开始升高，而抗炎细胞因子脂联素水平则出现下降。值得注意的是，该组内皮功能与血清一氧化氮水平在造模6周后即开始降低；造模12周时，高脂饲料组大鼠的收缩压与脂质过氧化水平开始升高。此外，本研究发现内脏总脂肪质量与内皮功能呈负相关，与收缩压呈正相关。
研究结论：本研究结果阐明了肥胖相关有害效应的动态变化过程及其相关性。