姜黄素对大鼠肾毒血清肾炎肾组织细胞外基质积聚的影响

Effect of curcumin on extracellular matrix accumulation in the glomeruli in nephrotoxic sera nephritis rats

目的 :观察姜黄素是否抑制肾炎大鼠肾组织Ⅳ型胶原和纤维连接蛋白 (fibronectin ,FN)的积聚而对肾脏起保护作用。方法 :72只雄性SD大鼠随机分成 3组 ,每组 2 4只。对照组尾静脉及腹腔注射生理盐水作对照 ;模型组尾静脉注射肾毒血清0 .5ml/d ,连用 2d ,腹腔注射二甲亚砜 0 .5ml·kg-1·d-1;姜黄素组尾静脉注射肾毒血清 0 .5ml/d ,连用 2d ,同时腹腔注射姜黄素 5 0mg·kg-1·d-1。分别于第 3、7、14、2 8天各处死 6只大鼠 ,部分肾组织福尔马林固定、石蜡包埋后进行免疫组织化学染色。结果 :对照组大鼠肾小球基膜Ⅳ型胶原以及FN染色弱阳性。模型组大鼠肾小球Ⅳ型胶原和FN沉积的范围随着病程的进展逐渐增多 ,与相应时间对照组比较有显著差异 (P <0 .0 1)。姜黄素组肾小球Ⅳ型胶原和FN沉积的范围亦随时间的发展逐渐扩大 ,然而Ⅳ型胶原较同期模型组比较染色范围却明显缩小 (P <0 .0 1) ,而FN于 7d后才比模型组减少 (P <0 .0 1)。结论

Objective:To observe whether curcumin could inhibit the accumulation of the collagen Ⅳ and fibronectin in the glomeruli in nephrotoxi sera nephritis rats. Methods:Seventy-two healthy male Sprague-Dawley rats were divided into three groups, with 24 animals in each group. For normal control group, normal saline (0.5 ml/d) was injected through intra-caudal-vein for two days, and at the same time normal saline (0.5 ml/kg) was also daily administered intraperitoneally. For nephrotoxic sera nephritis group, nephrotoxic sera (0.5 ml/d) was injected through the tail vein for two days and dimethyl sulfoxide (0.5 ml/kg) was given intraperitoneally daily. For curcumin group, nephrotoxic sera was injected as above and meanwhile curcumin (50 mg·kg -1·d -1) was administered intraperitoneally every day. Six rats in each group were killed on the 3rd, 7th, 14th and 28th day. Their renal tissue was fixed in 10% formalin for examining the expression of collagen Ⅳ and fibronectin. Results:Minimal staining of collagen Ⅳ and fibronectin was detected in the basement membrane of normal control rats glomeruli. In the nephrotoxic sera nephritis rats and curcumin treated nephrotoxic sera nephritis rats, the accumulation of collagen Ⅳ and fibronectin was increased progressively, with significant difference in the accumulation of collagen Ⅳ(P <0.01) between these two groups at the same time points, while the significant difference in fibronectin accumulation (P <0.05) appeared only after the 7th days. Conclusion:Curcumin can reduce the accumulation of collagen Ⅳ and fibronectin in the glomeruli. Hence we postulated that curcumin might have beneficial effect for retarding glomerulosclerosis.