CAJ | 학술논문

目的：本研究拟应用醛固酮受体拮抗剂干预肥胖致肾损伤小鼠模型，以期初步探讨醛固酮在肥胖相关性肾小球病（obesity?related glomerulonephropathy, ORG）中的作用。方法雄性C57BL/6J小鼠分为：对照组（10只），予10%脂肪含量普通饲料喂养；模型组（10只）和干预组（12只），予60%高脂饲料喂养。8周后，对照组和模型组予60%丙二醇10 ml·kg-1·d-1皮下注射，干预组予螺内酯20 mg·kg-1·d-1皮下注射。检测理化指标及肾组织病理，实时定量PCR及Western印迹检测足细胞标志蛋白的mRNA和蛋白变化。结果与对照组相比，12周末模型组小鼠体质量、肾质量、Lee氏指数、脂肪指数、血三酰甘油、血胆固醇、肌酐清除率、12 h尿蛋白量均明显上升（P＜0.05）；肾小球平均直径及肾小管损伤面积及足突宽度均明显增大（P＜0.05）；肾组织nephrin、podocin、podoplanin、podocalyxin mRNA及蛋白相对表达量下调（P＜0.05）。螺内酯干预后，上述指标均改善。结论醛固酮可损伤足细胞，参与ORG的发生，而抗醛固酮干预可改善上述过程，故为应用醛固酮受体拮抗剂治疗ORG提供了初步实验依据。
목적：본연구의응용철고동수체길항제간예비반치신손상소서모형，이기초보탐토철고동재비반상관성신소구병（obesity?related glomerulonephropathy, ORG）중적작용。방법웅성C57BL/6J소서분위：대조조（10지），여10%지방함량보통사료위양；모형조（10지）화간예조（12지），여60%고지사료위양。8주후，대조조화모형조여60%병이순10 ml·kg-1·d-1피하주사，간예조여라내지20 mg·kg-1·d-1피하주사。검측이화지표급신조직병리，실시정량PCR급Western인적검측족세포표지단백적mRNA화단백변화。결과여대조조상비，12주말모형조소서체질량、신질량、Lee씨지수、지방지수、혈삼선감유、혈담고순、기항청제솔、12 h뇨단백량균명현상승（P＜0.05）；신소구평균직경급신소관손상면적급족돌관도균명현증대（P＜0.05）；신조직nephrin、podocin、podoplanin、podocalyxin mRNA급단백상대표체량하조（P＜0.05）。라내지간예후，상술지표균개선。결론철고동가손상족세포，삼여ORG적발생，이항철고동간예가개선상술과정，고위응용철고동수체길항제치료ORG제공료초보실험의거。
Objective To examine whether aldosterone contribute to obesity related glomerular disease. Methods C57BL/6J mice were randomly divided into three groups: a control group (low?fat?diet, n=10), a model group (high?fat?diet, n=10) and a intervention group (high?fat?diet, n=12). After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone (SPL).The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real?time PCR and Western blotting, respectively. Results Compared with the control group, body weight, kidney weight, Lee ’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up ? regulated (P<0.05); The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down?regulated in model group (P<0.05). Meanwhile, these changes were attenuated by SPL. Conclusion Aldosterone can participate in the process of obesity? related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.