Tumor necrosis factor-α blockade ameliorates diabetic nephropathy in rats.
Tumor necrosis factor-α blockade ameliorates diabetic nephropathy in rats.
复制标题
肿瘤坏死因子-α 阻断可改善大鼠糖尿病肾病
DOI：
10.1093/ckj/sfz137
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发表时间：
2021-01
影响因子：
4.6
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Cheng D;Liang R;Huang B;Hou J;Yin J;Zhao T;Zhou L;Wu R;Qian Y;Wang F
肾小管损伤在糖尿病肾病（DN）的发展中起着至关重要的作用，但目前的DN治疗不能对抗肾小管损伤。本研究旨在研究肿瘤坏死因子（TNF）-α抑制剂是否能保护糖尿病大鼠肾小管损伤并探讨相关机制。 收集并分析12例DN患者和5例对照组的肾活检组织。链脲佐菌素（STZ）诱导的糖尿病大鼠用TNF-α抑制剂治疗12周。检测肾功能、蛋白尿、组织学损伤、肾组织TNF-α信使RNA（mRNA）和NOD-（核苷酸结合）、LRR-（结构域样受体）和含pyrin结构域蛋白3（NLRP 3）炎性小体。糖尿病合并肾小管间质损伤（TIN）患者肾小管TNF-α mRNA表达和NLRP 3炎性小体表达均明显增高（P < 0.05）。TNF-α抑制剂可减少STZ诱导的糖尿病大鼠蛋白尿、肾小球和肾小管损伤（P < 0.05）。重要的是，TNF-α抑制显著减少肾小管中的NLRP 3炎性小体（P < 0.05）。TNF-α抑制可降低肾小管IL-6和IL-17 A mRNA的表达。TNF-α抑制通过抑制NLRP 3炎性小体对DN大鼠TIN的保护作用未来的研究可能会使用前瞻性观察关注TNF-α抑制的临床保护作用。
Tubular injury plays a critical role in the development of diabetic nephropathy (DN), but current DN therapies do not combat tubular injury. This study was conducted to investigate if tumor necrosis factor (TNF)-α inhibition protects against tubular injury in diabetic rats and to examine the associated mechanisms. Kidney biopsy tissues were collected and analyzed from 12 patients with DN and 5 control subjects. Streptozotocin (STZ)-induced diabetic rats were treated with a TNF-α inhibitor for 12 weeks. Renal function, albuminuria, histological injury, renal TNF-α messenger RNA (mRNA) and the NOD- (nucleotide-binding), LRR- (domain-like receptor) and pyrin domain-containing protein 3 (NLRP3) inflammasome were assessed. Diabetic patients with tubulointerstitial injury (TIN) presented with higher renal tubular expression of TNF-α mRNA and the NLRP3 inflammasome (P < 0.05). TNF-α inhibition reduced albuminuria, glomerular injury and tubular injury in STZ-induced diabetic rats (P < 0.05). Importantly, TNF-α inhibition significantly reduced the NLRP3 inflammasome in tubules (P < 0.05). Moreover, TNF-α inhibition decreased expression of tubular interleukin (IL)-6 and IL-17A mRNA. TNF-α inhibition protects against TIN by suppressing the NLRP3 inflammasome in DN rats. Future studies may focus on the clinical protective effects of TNF-α inhibition using prospective observation.
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影响因子：
3.4
作者：
Zeni L;Norden AGW;Cancarini G;Unwin RJ
通讯作者：
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影响因子：
5.2
作者：
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Krolewski, Andrzej S.
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作者：
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通讯作者：
Hoffman, Hal M.
影响因子：
4
作者：
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通讯作者：
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