激素耐药型原发性肾病综合征患儿肾间质微血管密度与钙敏感受体表达变化

目的探讨糖皮质激素（GC）耐药原发性肾病综合征（PNS）患儿肾小管上皮细胞钙敏感受体（CaSR）表达与肾小管间质损害、钙磷代谢紊乱、肾小管间质周围微血管密度之间的关系。方法将人选的36例PNS患儿按是否糖皮质激素耐药分两组，激素敏感组（16例），激素耐药组（20例），采用半定量评分法对肾小管间质病理损害程度进行评价，利用全自动生化仪测定血清钙（ca）、磷（P）浓度，免疫组化法检测肾小管上皮CaSR表达与肾小管间质周围微血管密度。结果激素耐药组患儿血清P水平（2．26±0．15）mmol／L]高于激素敏感组（1．90±0．12）mmol／L，P〈0．05]；激素敏感组患儿。肾小管上皮细胞CaSR表达（4．63±0．78）低于激素耐药组（6．56±1．22，P〈0．05），微血管密度高于激素耐药组（2．98±0．35VS2．02±0．24，P〈0．05）；肾小管间质轻度损害时，激素敏感组肾小管上皮细胞CaSR表达（4．15±0．58）低于耐药组（4．264-0．61），但差异无统计学意义（P〉0．05），微血管密度则高于耐药组（3．12±0．33，3．01±0．21），但差异无统计学意义（P〉0．05）；肾小管间质中度损害时，激素敏感组（5．35±0．64）肾小管上皮细胞CaSR表达低于耐药组（7．37±0．81，P〈0．01），微血管密度则明显高于耐药组（2．81±0．16，2．02±0．14，P〈0．05）；与轻、中度。肾小管间质损害的激素耐药患儿相比，重度肾小管间质损害的激素耐药患儿肾小管上皮细胞CaSR表达（11．46±1．38）显著增高，微血管密度（1．15±0．11）显著降低（均P〈0．01）。结论糖皮质激素耐药型PNS患儿肾小管上皮细胞CaSR表达增高与肾小管周围微血管密度下降，可能是由于GC的细胞毒作用损害肾小管上皮细胞后，继发钙磷代谢异常与血管内皮损害所致。

Renal interstitial microvascular density and calcium-sensing receptor expression in children with steroid-resistant nephrotic syndrome

Objective Study the relationship among CaSR expression, tubulointerstitial damage,metabolic disturbance of calcium and phosphorus and microvascular density around the tubulointerstitium in children with steroid-resistant nephrotic syndrome.Methods 36 cases of children with primary nephrotic syndrome were divided into hormone-sensitive group and steroid-resistant group.Semi-quantitative scores for tubulointerstitial pathological evaluation of the extent of damage, automatic biochemical analyzer for the determination of serum calcium (Ca), phosphorus (P) concentration of renal tubular epithelial CaSR expression and microvessel microvascular density around the tubulointerstitium were determined by immunohistochemical assay.Results More severe the tubulointerstitial damage, lower level of serum Ca and higher level of serum P were observed (2.26 ± 0.15) mmol/L]in children of the steroid-resistant group and the steroid-sensitive group (1.90 + 0.12) mmol/L, P ＜ 0.05].CaSR expression (4.63 + 0.78) of renal tubular epithelial cells in the steroid- sensitive group was significantly lower than that in the steroid-resistant group (6.56 + 1.22, P ＜ 0.05), but microvascular density was significantly higher in the steroid- sensitive group(2.98 +0.35 vs 2.02 +0.24, P ＜0.05).When the tubulointerstitial damage was mild, CaSR expression (4.15 +0.58) in renal tubular epithelial cells in the steroid- sensitive group (4.26 ±0.61) was lower than the steroid-resistant group(3.12 ± 0.33; 3.01 ± 0.21), and microvascular density was higher,but the difference was not significant(P ＞0.05).In the moderate tubulointerstitial damage, CaSR expression in renal tubular epithelial cells in the steroid- sensitive group (5.35 ± 0.64) was significantly lower than the resistant group (7.37 +0.81, P ＜0.01), and microvascular density was significantly higher than the resistant group (2.81 ±0.16, 2.02 ±0.14, P ＜0.05).Compared by mild and moderate tubulointerstitial damage in children with the steroid-resistant, CaSR expression (11.46 ± 1.38) in children with severe tubulointerstitial damage was significantly increased, and microvascular density (1.15 ± 0.11) was significantly decreased (all P ＜ 0.01).Conclusions CaSR expression was increased and microvascular density around the tubulointerstitium was decreased in children with steroid-resistant nephrotic syndrome.Dut to steroid resistance, the cytotoxic of steroid damaged the renal tubular epithelial cells, the metabolic disturbance of calcium and phosphorus and the damage of blood vessel endothelium finally resulted in severe tubulointerstitial damage.