Background

Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM) and is associated with early changes in renal angiotensin II (ANG II). These changes were evaluated using ANG II blocker valsartan early from week two of diabetes (experiment I, renoprotective) and late from week nine of diabetes (experiment II, renotherapeutic) to the end of both experiments at week twelve.

Methods and results

In both experiments, adult male Wister rats were divided into (i) vehicle group; (ii) valsartan received oral 30 mg/Kg/day; (iii) diabetic received single 50 mg/Kg intraperitoneal streptozotocin injection; (iv) renoprotection, diabetic rats received valsartan treated in experiments I and II. DM effects on urine albumin excretion, blood pressure, and renal ANG II were measured. Urinary nephrin, kidney injury molecule-1 (KIM-1), renal angiopoietin-like protein 2 (ANGPTL2), and toll-like receptor 4 (TLR 4) mRNA expression were tested. DM-initiated fibrotic markers integrin, α-smooth muscle actin expression, and collagen IV and apoptotic protein caspase 3 were tested. DM induced early changes starting from week four in the tested variables. At week twelve, in both experiments, valsartan intervention showed a significant reduction in ANG II, ANGPTL2, TLR 4 and integrin expression and improvement in albuminuria, blood pressure, urinary biomarkers, fibrotic and apoptotic markers.

Conclusions

Changes leading to DN starts early in the disease course and ANG II reduction decreased the expression of ANGPTL2 and integrin which preserve the glomerular barrier. Blocking ANG II was able to decrease TLR 4 and inflammatory cytokines leading to decreasing DN.

中文翻译：

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阻断血管紧张素 2 受体通过减轻 ANGPTL2/TL4/NF-κB 表达减轻糖尿病肾病

背景

糖尿病肾病 (DN) 是糖尿病 (DM) 的结果，并且与肾血管紧张素 II (ANG II) 的早期变化有关。从糖尿病第 2 周早期（实验 I，肾脏保护）和糖尿病第 9 周晚期（实验 II，肾脏治疗）到第 12 周两个实验结束，使用 ANG II 阻滞剂缬沙坦评估了这些变化。

方法和结果

在这两个实验中，成年雄性 Wister 大鼠被分为 (i) 载体组；(ii) 缬沙坦口服 30 mg/Kg/天；(iii) 糖尿病患者接受单次 50 mg/Kg 链脲佐菌素腹腔注射；(iv) 肾脏保护，糖尿病大鼠在实验 I 和 II 中接受缬沙坦治疗。测量了 DM 对尿白蛋白排泄、血压和肾 ANG II 的影响。检测了尿 nephrin、肾损伤分子 1 (KIM-1)、肾血管生成素样蛋白 2 (ANGPTL2) 和 toll 样受体 4 (TLR 4) mRNA 表达。测试了 DM 引发的纤维化标志物整合素、α-平滑肌肌动蛋白表达、胶原蛋白 IV 和凋亡蛋白半胱天冬酶 3。从第四周开始，DM 在测试变量中引起了早期变化。在第 12 周，在两个实验中，缬沙坦干预均显示 ANG II、ANGPTL2、

结论

导致 DN 的变化在病程早期就开始了，而 ANG II 的减少降低了 ANGPTL2 和整合素的表达，从而保护了肾小球屏障。阻断 ANG II 能够降低 TLR 4 和炎性细胞因子，从而降低 DN。