肥胖Zucker大鼠淋巴壁重塑与全身和组织相关炎症

在人类中，淋巴功能障碍和肥胖似乎具有相互关系，例如淋巴水肿可引起脂肪沉积，肥胖可损害淋巴功能。最近对老鼠的研究表明，高脂肪饮食引起的肥胖损害了尾巴和后肢的淋巴引流。淋巴也会变得过度渗透，在患有肥胖症和糖尿病的db/db小鼠中渗出淋巴。这些研究表明淋巴功能障碍与肥胖相关，但其病理生理机制尚不清楚。本研究的目的是探讨肥胖在多大程度上引起大鼠肠系膜集淋巴管壁的炎症和重塑。本研究采用ZUCKER-Leprafa(肥胖)和ZUCKER-Leprafa /+(瘦)雄性和/或雌性大鼠，符合FASEB关于在研究和教育中使用动物的原则声明。年龄组别包括8周、12周及26-32周。在37°C白蛋白生理盐溶液(不含Ca2+的APSS)浴中，通过收集分离的淋巴管并将其安装在电阻匹配的玻璃微管上，测量被动管壁力学，管腔压力从1- 5cm H2O移至1- 5cm H2O。取肠系膜弓部脂肪组织和收集的淋巴组织，用4%多聚甲醛固定，石蜡包埋切片，用大鼠特异性CD68抗体(巨噬细胞标记物)和小穴蛋白-1抗体(脂肪细胞标记物)免疫染色，定量冠状结构(CLSs)。使用67大鼠生物标志物检测服务- RayBiotech收集血清和淋巴周围脂肪组织(PLAT)并分析炎症生物标志物。 Average lymphatic wall thickness, wall:lumin ratio (X100) and medial cross sectional area were significantly greater in obese versus lean male rats at all ages. Many CLSs were observed surrounding mesenteric collecting lymphatics isolated from obese male 12 and 26-32 wk rats. Additionally, CLSs significantly increased with age. In an analyses of serum biomarkers obtained from 12 wk old lean and obese, male and female rats, we observed that many of the markers in PLAT (IL-6, IL-13, adiponectin) and in serum (GM-CSF, IL-4, Gas1) were differentially regulated by obesity and sex. The data support the ideas that obesity can permit changes to passive wall mechanics that can lead to a structural remodeling of lymphatic collecting vessels and that obesity is associated with both systemic and tissue-associated inflammation (PLAT) in both male and female Zucker rats.