高脂高糖高胆固醇饮食对小型猪肾脏细胞外基质表达的影响

Differential Expression of Extracellular Matrix in the Kidneys of Diabetic Mini-pigs Induced by High-fat/high-sucrose/high-cholesterol Diet

为研究高脂高糖高胆固醇(HFSCD)诱导的2型糖尿病小型猪肾脏细胞外基质(ECM)的表达情况,将10头广西巴马小型猪分别喂正常和HFSCD饲料,收集血、尿液,测定其生化指标,进行口服葡萄糖耐量试验。5个月后取部分肾组织,行H.E和Masson染色,免疫组织化学方法检测ECM相关蛋白的表达。结果表明,喂养HFSCD后,小型猪血糖、血脂和胰岛素明显升高,出现胰岛素抵抗和β细胞功能紊乱;尿糖和微量白蛋白升高;肾脏纤维连接蛋白(FN)和Ⅳ型胶原的表达明显增加,而Ⅰ型胶原无表达。这说明HFSCD喂养广西巴马小型猪5个月能成功建立早期糖尿病肾病模型,促进FN和Ⅳ型胶原的表达。

To investigate the differential expressions of extraeellular matrix in the kidneys of type 2 diabetic mini-pigs induced by high-fat/high-sucrose/high-cholesterol diet （HFSCD）, 10 male Guangxi Bama mini-pigs were fed normal control diet or HFSCD （5 for each group）, and biochemical parameters in blood and urine and oral glucose tolerance test were monitored after the feeding programme. Five months later, each left kidney was removed, routinely stained with HE and Masson＇ s trichrome staining. Extracellular matrix expression in the kidneys was determined by fibronectin, type Ⅰ and type Ⅳ collagens immunostaining. Feeding HFSCD to mini-pigs markedly caused hyperglycaemia, hyperinsulinaemia, dyslipidaemia, insulin resistance and beta cell dysfunction. Albuminuria, glucosuria, extracellular matrix accumulation were observed in HFSCD-fed mini-pigs. The expression of fibronectin and type Ⅳ collagen was significantly increased in the kidneys of the HFSCD group, while immunoreactivity of type Ⅰ collagen showed no expression in HFSCD- and CD-fed pigs. Thus, we have shown that feeding HFSCD to the Guangxi Bama mini-pigs for 5 months can induce early-stage diabetic nephropathy, and increase fibronectin and type Ⅳ collagen expression.