替米沙坦对单纯性肥胖小鼠血清脂联素及尿微量白蛋白的影响

Effect of telmisartan on serum adiponectin, urine microalbumin of obese mice

目的 探讨替米沙坦对单纯性肥胖小鼠血清脂联素及尿微量白蛋白（mAlb）的影响,旨在寻找肥胖相关性肾病治疗的新思路.方法 选取8周龄雄性OB小鼠24只及同系C57小鼠8只.按体质量将OB小鼠分层随机分为3组：模型组（M组）,替米沙坦治疗组（T1组）,氯沙坦治疗组（T2组）,高脂饲料喂养.C57小鼠为对照组（C组）,普通饲料喂养,连续12周.分别于实验前后检测小鼠血清脂联素、血糖及24h尿微量蛋白（mAlb）水平.实时定量PCR （qRT-PCR）法检测肾组织过氧化物酶体增殖物活化受体γ（PPARγ） mRNA的表达水平.HE染色后光镜下观察肾组织病理改变,测定肾小球直径.比较4组小鼠体质量、血清脂联素、血糖、尿mAlb、肾组织PPARγmRNA、肾脏湿重及肾小球直径的差异,Pearson相关性分析血清脂联素、尿mAlb与血、尿生化病理指标的相关性.结果 与C组比较,M组小鼠尿mAlb排泄量增加、血清脂联素水平下降、PPARγ mRNA表达减少（均P＜0.01）;尿mAlb排泄量与血清脂联素、PPARγ mRNA水平呈负相关（r=-0.773,P＜0.01;r=-0.469,P＜0.01）.与M组比较,T1组小鼠尿mAlb排泄量减少、血清脂联素水平及PPARγmRNA表达增高（均P＜0.05）;与T2组比较,T1组小鼠尿mAlb排泄量减少、血清脂联素水平及PPARγmRNA表达增多（均P＜0.05）;与M组比较,T2组小鼠尿mAlb排泄量降低（P=0.01）.肾组织病理检查结果提示,M组小鼠肾小球体积增大,部分伴有局灶节段性硬化;T1组小鼠无肾小球体积增大及局灶节段性硬化改变;T2组小鼠肾小球体积增大及伴有局灶节段性硬化.结论 替米沙坦可降低单纯性肥胖小鼠尿白蛋白,其机制可能与替米沙坦激活PPARγ,提高血清脂联素水平有关.

Objective To evaluate the effect of telmisartan on serum adiponectin and urine microalbumin（mAlb） level by administrating it to mice with simple obesity, so as to explore new therapies for obesity-related kidney diseases.Method A total of 24 8-week-old male OB mice and 8 8-week-old male C57 mice were selected for this study.The genetic background of OB mouse was C57 mouse, but the lepin gene was deleted in OB mouse.OB mice were randomly divided into 3 groups by body weight and fed with high-fat diet for 12 weeks： model group （M group）, telmisartan group （T1 group） and losartan group （T2 group）.C57 mice acted as control and were fed with general diet for 12 weeks.Serum adiponectin and blood glucose levels were measured before and after treatment.24 h urine was collected to measure urine mAlb.Quantitative real-time PCR （qRT-PCR） was used to measure the expression level of peroxisome proliferators-activated receptors gamma mRNA（PPARγ mRNA）.HE stain was used to observe the morphological changes of kidney and measure the glomerular diameter.Body weight, serum adiponectin level, blood glucose level, urine mAlb level, expression level of kidney PPARγ mRNA, kidney wet weight and glomerular diameter of 4 groups were compared and a correlation analysis was carried out by Person correlation coefficient.Results Compared with C group, the urine mAlb level in M group increased （P〈0.01）, serum adiponectin level and the expression level of kidney PPARγ mRNA in M group decreased （P 〈 0.01）;The urine mAlb level was negatively correlated with serum adiponectin level and expression of kidney PPARγmRNA （r=-0.773,P 〈 0.01;r=-0.469, P 〈 0.01）.The urine mAlb level in T1 group was lower than M group （P 〈 0.05）,serum adiponectin level and expression of kidney PPARγmRNA in T1 group were higher than M group （P 〈 0.05）.Compared with T2 group, the urine mAlb level in T1 group decreased, serum adiponectin level and expression of kidney PPARγ mRNA in T1 group increased （P 〈 0.05）;Compared with M group, the urine mAlb level in T2 group decreased （P=0.01）.The morphological changes of kidney：glomerular volume increase and focal segmental sclerosis were found in some mice in M group and T2 group.No glomerular volume increase and focal segmental sclerosis were observed in T1 group.Conclusions Telmisartan can reduce urine microalbumin, whose mechanism might be that telmisartan can active the PPARγand promote the level of serum adiponectin.