糖尿病大鼠肾上腺水通道蛋白1表达特征以及多b值扩散加权成像评估肾上腺损伤的价值

Investigation of aquaporin-1 expression and diffusion weighted imaging with multiple b values in adrenal gland in a rat model of diabetes mellitus

目的 探讨糖尿病大鼠肾上腺水通道蛋白1（AQP-1）表达特征及多b值DWI评估肾上腺损伤的价值.方法 取20只雄性SD大鼠采用电脑软件将动物随机分为对照组和糖尿病组,每组10只.对照组采用常规饲料喂养;糖尿病组采用高糖高脂饲料喂养.糖尿病组大鼠高糖高脂饲料喂养4周后腹腔注射小剂量（40 mg/kg）链脲佐菌素,对照组腹腔注射等量柠檬酸钠缓冲液.注射后第40天对大鼠行MRI检查,先行尾静脉血糖检测,血糖＞16.7 mmol/L认为建模成功.采用7.0 T MR扫描仪行18个b值（0~4500 s/mm2）的肾上腺DWI扫描,测量伪扩散系数（D＊）、纯扩散系数（D）和超高b值表观扩散系数（ADCuh）值.完成MRI检查后处死大鼠,行肾上腺病理和AQP-1免疫组织化学分析,测量AQP-1染色平均吸光度值.采用独立样本t检验比较糖尿病肾上腺和正常肾上腺间D＊值、D值、ADCuh值及AQP-1染色平均吸光度值的差异.结果 糖尿病组大鼠8只建模成功（2只死亡）.18只大鼠完成MRI扫描.肾上腺D＊图、D图和ADCuh图信号逐渐降低.糖尿病组肾上腺ADCuh值为（0.24±0.06）×10-3mm2/s,高于对照组肾上腺（0.18±0.07）×10-3mm2/s,差异有统计学意义（P＜0.05）;糖尿病组和对照组肾上腺间D＊、D值差异无统计学意义（P＞0.05）.糖尿病肾上腺细胞膜上和细胞基质内AQP-1免疫组织化学染色明显较对照组细胞增多.糖尿病组肾上腺AQP-1平均吸光度值高于对照组肾上腺,差异有统计学意义（P＜0.05）.结论 糖尿病大鼠肾上腺AQP-1的表达增加.超高b值DWI评估糖尿病肾上腺功能改变具有一定价值.

Objective To investigate the character of aquaporin-1（AQP-1）expression in adrenal gland in diabetes mellitus and evaluate adrenal gland damage and function alterations by DWI with multiple b values. Methods Twenty male Sprague-Dawley rats were randomly selected by computer and randomized into 2 groups：untreated controls（n=10）and diabetes（DM）（n=10）. Rats in diabetes group were fed with high-sucrose and high-fat diet, controls were fed with common diet. After fed with high-sucrose and high-fat diet for 4 weeks, rats in diabetes group were injected with streptozotocin（STZ）. Forty days after diabetes induction with streptozotocin（STZ）, MR imaging was performed in a 7.0 T scanner. Venous blood from the tails was collected before MRI scan to measure blood glucose, blood glucose more than 16.7 mmol/L wasregarded as diabetic status. All the rats underwent DWI with 18 b values（0 to 4500 s/mm2）. Maps of pure diffusion coefficients（D）, pseudo-diffusion coefficients（D＊）and ultra-high ADC（ADCuh）were acquired. Rats were sacrificed after MRI scan for adrenal gland histopathology, AQP-1 immunohistochemistry analysis and AQP-1 optical density（OD）measurements. Student t test was used to compare the difference of D＊, D, ADCuh and OD of AQP-1 between two groups. Results Eight diabetic animals developed hyperglycemia（two rats died during the modeling process）. MRI scan was performed in all of the 18 rats. Signal intensity of D＊map, D map and ADCuh map decreased gradually. ADCuh increased significantly in DM animals（0.24 ± 0.06） × 10-3mm2/s compared with control animals（0.18 ± 0.07） × 10-3 mm2/s（P〈0.05）, whereas there was no significant difference found between the two groups in their respective D＊and D values（P〉0.05）. There was a noticeable increase in the AQP-1 labeling in the adrenal cell membrane and cytoplasm in DM animals compared with control animals. DM rats showed an increased OD value of AQP-1 in adrenal gland compared with the control animals（P〈0.05）. Conclusions We found significantly higher AQP-1 expression in adrenal gland in DM animals compared with controls. Ultra-high b-Values DWI may work as a useful way for noninvasive evaluation the change of adrenal function in DM.