Jandeleit-Dahm K, Cao Z, Cox A J, Kelly D J, Gilbert R E, Cooper M E
Department of Medicine, University of Melbourne, Austin, Victoria, Australia.
Kidney Int Suppl. 1999 Jul;71:S31-6. doi: 10.1046/j.1523-1755.1999.07109.x.
It has been suggested that lipids promote renal injury and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors confer renoprotection in certain renal diseases, including diabetic nephropathy.
Sprague-Dawley rats were randomized to sham, subtotal nephrectomy (STNx) or STNx + atorvastatin groups. After 12 weeks, proteinuria, renal function, glomerular injury, renal transforming growth factor-beta (TGF-beta) gene expression and macrophage (ED1-positive cells) accumulation were assessed. In addition, the effects of HMG CoA reductase in human diabetic nephropathy were reviewed.
Atorvastatin therapy was associated with a modest reduction in proteinuria and glomerulosclerosis without influencing lipid levels or renal function in STNx rats. These effects were associated with decreased renal TGF-beta 1 gene expression and less glomerular and tubulointerstitial macrophage accumulation. The renoprotective effects of HMG CoA reductase inhibitors in both insulin- and non-insulin-dependent diabetic subjects with either incipient or overt nephropathy appear to be highly variable.
HMG CoA reductase inhibition appears to confer renoprotection via effects on prosclerotic cytokines such as TGF-beta and macrophage accumulation, independent of their lipid-lowering properties. The role of lipid-lowering agents in early or overt diabetic nephropathy remains to be fully ascertained.
有研究表明脂质会促进肾损伤，且3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶抑制剂在某些肾脏疾病（包括糖尿病肾病）中具有肾脏保护作用。
将Sprague-Dawley大鼠随机分为假手术组、次全肾切除（STNx）组或STNx +阿托伐他汀组。12周后，评估蛋白尿、肾功能、肾小球损伤、肾脏转化生长因子-β（TGF-β）基因表达和巨噬细胞（ED1阳性细胞）积聚情况。此外，还回顾了HMG CoA还原酶在人类糖尿病肾病中的作用。
在STNx大鼠中，阿托伐他汀治疗与蛋白尿和肾小球硬化的适度减轻相关，而不影响血脂水平或肾功能。这些作用与肾脏TGF-β1基因表达降低以及肾小球和肾小管间质巨噬细胞积聚减少有关。HMG CoA还原酶抑制剂在胰岛素依赖型和非胰岛素依赖型糖尿病肾病初发或显性患者中的肾脏保护作用似乎差异很大。
HMG CoA还原酶抑制似乎通过对促硬化细胞因子（如TGF-β）和巨噬细胞积聚的影响而发挥肾脏保护作用，与其降脂特性无关。降脂药物在早期或显性糖尿病肾病中的作用仍有待充分确定。
