Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, China.
J Pharmacol Sci. 2014;125(1):59-67. doi: 10.1254/jphs.13173fp. Epub 2014 Apr 16.
Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-κB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.
越来越多的证据表明，巨噬细胞诱导肾小管间质损伤。白芍总苷（TGP）是从白芍中提取的，已在糖尿病肾病中表现出抗炎活性。本研究将探讨 TGP 对链脲佐菌素诱导的糖尿病大鼠肾小管间质的保护作用及其机制。TGP 以 50、100 和 200mg·kg(-1)·d(-1)的剂量口服给药 8 周。定量肾小管间质损伤，然后通过免疫组织化学分析肾α-平滑肌肌动蛋白（α-SMA）、E-钙黏蛋白（E-cad）表达、核因子 kappa B（NF-κB）-p-p-65(+)、Toll 样受体（TLR）2(+)和 ED-1(+)细胞在肾小管间质中的浸润。通过双重免疫组织化学染色检测肾 TLR2(+)巨噬细胞。Western blot 用于检测 TLR2 表达。组织学上，糖尿病肾脏中 TLR2(+)、NF-κB-p-p-65(+)、ED-1(+)细胞和 ED-1(+)TLR2(+)细胞（巨噬细胞）明显积聚，TGP 治疗可减轻这种积聚。同时，肾小管间质损伤得到改善，α-SMA 表达降低，E-cad 表达升高。Western blot 分析显示，糖尿病大鼠肾脏 TLR2 蛋白表达明显增加，而 TGP 治疗则降低了其表达。我们的研究表明，TGP 可通过抑制巨噬细胞浸润增加和 TLR2 表达来预防糖尿病大鼠的肾小管间质损伤。
