Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy.

Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy.
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Toll 样受体 4 参与大黄酸对免疫球蛋白 A 肾病的保护作用。

DOI:
10.4103/0253-7613.150319
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发表时间:
2015-01
影响因子:
2.4
通讯作者:
Zhu Q
Zhu Q
中科院分区:
医学4区
文献类型:
--
作者:
Chen X;Peng S;Zeng H;Fu A;Zhu Q

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目的:探讨大黄酸对免疫球蛋白A肾病大鼠肾组织TLR4、TLR9、转化生长因子-β1(TGFR-β1)表达的影响及大黄酸对肾组织病理改变的保护作用。采用牛血清白蛋白-脂多糖-四氯化碳-4法建立IgAN模型。雄性SD大鼠32只,随机分为对照组、IgAN模型组、大黄酸预防组和大黄酸治疗组。用全自动生化分析仪检测大鼠24 h尿蛋白(UP)、肌酐、尿素、丙氨酸氨基转移酶(ALT)、总蛋白(TP)含量,苏木精-伊红染色和高碘酸-席夫染色观察肾脏病理变化。免疫荧光染色检测肾小球内IgA沉积。采用实时定量聚合酶链式反应和免疫组织化学方法检测肾组织中TLR4、TLR9、转化生长因子β1信使核糖核酸和蛋白表达。免疫球蛋白肾病模型大鼠的生化指标结果显示,模型组大鼠24 h尿蛋白排泄量和ALT浓度明显高于对照组(P<0.05),TP浓度显著低于对照组(P<0.05)。IgAN组肾小球系膜区可见颗粒样或块状IgA沉积,肾小球细胞增多,系膜基质增生,肾小管间质纤维化。大黄酸预防和治疗均能改善生化指标,减轻肾脏病理损伤。模型组大鼠肾组织中TLR4、β-1的表达显著增加,而TLR9的表达无明显变化(P>0.05)。大黄酸预防和治疗均可抑制TLR4和转化生长因子-β1的表达。大黄酸能明显改善IgA肾病大鼠血、尿生化指标,减轻肾小球病变和肾小管间质纤维化。其机制可能与抑制肾脏TLR4和转化生长因子-β-1的分泌有关。
The objective was to investigate the protective effects of rhein on renal histology change and the effects of rhein on renal tissue toll-like receptor (TLR) 4, TLR9, transforming growth factor-β1 (TGF-β1) expression in immunoglobulin A nephropathy (IgAN) rats. Bovine serum albumin-lipopolysaccharide-carbon tetrachloride 4 method was used to establish IgAN model. Thirty-two male sprague dawley rats were randomly divided into the control group, IgAN model group, rhein-prevented group, and rhein-treated group. 24-h urinary protein (UP), creatinine, urea, alanine aminotransferase (ALT), total protein (TP) contents in the serum of rats were detected with automatic biochemical analyzer and renal pathological changes were observed by the hematoxylin and eosin and periodic acid-Schiff staining. The glomerular deposition of IgA was measured by immunofluorescence staining. Real-time polymerase chain reaction and immunohistochemistry were used to detect renal tissue contents of TLR4, TLR9, TGF-β1 messenger ribonucleic acid and protein expression. The biochemical parameters results of IgAN model rats showed that the 24-h UP excretion and ALT concentration were much higher, and TP concentration was much lower than those of the control group (P < 0.05). Granule-like or mass-like IgA depositions in the mesangial area, glomerular hypercellularity, hyperplasia of mesangial matrix, and tubulointerstitial fibrosis were found in IgAN group. Rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions. Rhein significantly improved the serum and urine biochemical parameters, and attenuated the glomerular pathological changes and tubulointerstitial fibrosis in IgAN rats. The mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.
DOI: 10.1084/jem.157.2.572
发表时间: 1983-02-01
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