高糖高脂饮食对兔肾小管间质纤维化的影响

The Effects of High-Sucrose and High-Fat Diet on Tubulointerstitial Fibrosis in New Zealand White Rabbits

为研究高糖高脂饮食对新西兰兔(Oryctolagus cuniculus)肾小管间质纤维化的影响,将20只雄兔随机均分2组,分别喂正常饲料(对照组)和高糖高脂饲料(模型组),每月测空腹血糖和甘油三酯(TG),5个月后取尿液测尿糖、微量白蛋白(mAlb)和N-乙酰β-氨基葡萄糖苷酶(NAG),H.E、VG染色观察肾髓质病理改变,计算肾小管间质纤维化指数(TIFI)和胶原纤维面积,免疫组化测Ⅳ型胶原、纤维连接蛋白(FN)和转化生长因子β1(TGF-β1)的蛋白表达。结果显示,与对照组相比,模型组血糖、TG、尿糖、mAlb和NAG上升(P<0.05或P<0.01);肾小管间质肿胀,炎症细胞浸润,胶原纤维面积增加(22.47%±5.66%vs.9.43%±3.03%,P<0.01),TIFI升高(2.369±0.6734vs.0.6810±0.2248,P<0.01);Ⅳ型胶原、FN和TGF-β1的表达显著增加(P<0.01)。上述结果说明,高糖高脂喂养兔5个月可导致肾小管、间质的结构和功能发生改变,细胞外基质表达增加,促进纤维化形成。

To study the effects of high-sucrose and high-fat diet on tubulointerstitial fibrosis, male New Zealand white rabbits（ Oryctolagus cuniculus） were randomly divided into two groups：the control group （n = 10, fed with normal chow） and the experimental model group （n = 10, fed with 37% sugar, 10% lard and 53% normal chow）. The levels of fasting plasma glucose and triglyceride were tested once a month. Urinary glucose, microalbumin, and N-acetyl-β-glucosaminidase （NAG） were measured at the end of the 5th month. The tubulointerstitial fibrosis index（TIFI） and the area of collagen fiber were calculated in the renal medulla with HE or VG staining respectively. The protein expression of type Ⅳ collagen,fibronectin and transforming growth factor β1 （TGF-β1） were determined by immunohistochemical staining. Feeding high-sucrose and high-fat diet to rabbits markedly caused hyperglycaemia, hypertriglyeeridemia, albuminuria, glucosnria, and increased urinary NAG levels（P 〈 0.05 or P 〈 0.01 ）. The edema,inflammatory cell infiltration and proliferation of collagen fiber were observed in tubulointerstitium of the experimental model group. The area of collagen fiber 22.47%±5.66% and the grade of TIFI 2. 369±0. 6734 were significantly higher in the experimental model group than those in the control group （9.43%±3.03% and 0. 6810±0. 2248, P 〈 0.01, respectively）. The protein expression of type IV collagen, fibronectin and TGF-β1 was significantly increased in renal medulla of the experimental model group compared to that of the control group （P 〈 0. 01 ）. Thus, these results suggest that high-sucrose and high-fat diet can injure the tubulointerstitial structure and function,increase the expression of extracellular matrix and accelerate the process of tubulointerstitial fibrosis in rabbits.