低蛋白加α-酮酸对慢性肾衰大鼠营养状况及肾间质纤维化的作用

目的观察低蛋白饮食(lowproteindiet,LPD)以及LPD+α-酮酸(α-ketoacid,α-KA)对腺嘌呤致慢性肾功能衰竭(chronicrenalfailure,CRF)大鼠模型营养状况及肾间质纤维化的作用。方法雄性Wistar大鼠46只分对照组(n=10),CRF模型组(n=36,以腺嘌呤150mg/kg.d灌胃6w制模)。CRF模型组造模成功后随机分正常蛋白(normalproteindiet,NPD)组、LPD组和LPD+α-KA组,于10w、14w末测定血肌酐(Scr)与尿素氮(BUN)、血浆钙(Ca)、磷(P)、白蛋白(Alb)、血红蛋白(Hb)、24h尿蛋白(24hUPro);Masson染色分析肾间质纤维化程度;免疫组化方法测定肾组织中α平滑肌肌动蛋白(α–SMA),RT-PCR方法测定肾组织α–SMAmRNA表达程度。结果CRF各组体重增长、Alb、Hb、Scr水平均无差异。10w时,LPD及LPD+α-KA组BUN水平显著低于NPD组。10w时,CRF各组Ca、P水平无差异。14w时,LPD及LPD+α-KA组血Ca显著高于NPD组,CRF各组血P无差异。10w、14w时,LPD及LPD+α-KA组24hUPro明显低于NPD组。CRF各组间质纤维化程度逐渐加重,LPD、LPD+α-KA组显著轻于NPD组;10w时,LPD与LPD+α-KA间差异不显著;14w时,LPD+α-KA组较LPD组轻(P<0.05)。10w时,LPD与LPD+α-KA比NPD组肾组织α-SMA表达减轻,两者之间没有差别,14w这种作用不明显。结论LPD+α-KA及LPD均能维持CRF动物营养状态正常,均能减缓肾间质纤维化,LPD+α-KA的作用更强。这可能与肾小管上皮-间充质转化(epithelialmesenchymaltransition,EMT)程度减轻有关。

EFFECTS OF LOW PROTEIN DIET SUPPLEMENTED WITH α-KETOACID ON NUTRITIONAL STATUS AND RENAL INTERSTITIAL FIBROSIS IN ADENINE-INDUCED CHRONIC RENAL FAILURE RATS

Objective To evaluate the effects of low proteins diet (LPD) supplemented with ketoacids(α-KA) on the nutritional status and renal interstitial fibrosis in comparison with conventional LPD in adenine induced chronic renal failure (CRF) rat model. Method Forty-six male Wistar rats were divided into two parts: normal control rats(n=10)and CRF rats(n=36),which were treated with 150 mg/(kg bw·d) adenine intragastrically. After 6 w,CRF rats were divided into three groups: (a)normal protein diet NPD (20% casein diet) group,n=12;(b)LPD (6% casein diet) group,n=12;(c)LPD+α-KA (5%casein +?1% α-KA)group,n=12. All the rats were sacrificed at 10,14 w. Body weight(BW),hemoglobin(Hb),albumin (Alb),serum creatinine(Scr),blood urea nitrogen(BUN),24h urine protein(24hUpro) were measured.Masson stain was performed to grade the extent of renal interstitial fibrosis. Immunohistochemistry and RT-PCR methods were used to evaluate the extent of expressions of α-smooth muscle actin (α-SMA). Results The levels of Scr,Hb and BW were not different among the three groups over time. 24hUpro in both LPD and LPD+α-KA groups were lower significantly than in NPD group. BUN levels of LPD and LPD+α-KA group were significantly lower than that in NPD group at 10w. Serum Ca levels of LPD and LPD+α-KA groups were significantly higher than that in NPD group at 14w. The extent of renal fibrosis in LPD and LPD+α-KA groups was milder than that in NPD group,much milder in LPD+α-KA (P<0.05). Expressions of α-SMA in LPD and LPD+α-KA group were also lower than that in NPD group. Conclusion LPD and LPD+α-KA not only sustain the nutritional status,but also ameliorate the renal fibrosis and epithelial-mesenchymal transition (EMT)in adenine-induced CRF rat model,and these effects of LPD+α-KA are better than LPD.