Toll样受体4在糖尿病肾病患者肾组织中的表达及厄贝沙坦的干预作用

发布时间：2018-11-04 11:38

【摘要】：目的探讨Toll样受体4(TLR4)信号通路与糖尿病肾病(DN)的关系及使用血管紧张素受体拮抗剂(ARB)干预对TLR4信号通路的影响,探讨其肾脏保护机制。方法研究对象为2012年7月至2014年6月在南昌大学第一附属医院肾内科住院的糖尿病肾病患者,使用ARB厄贝沙坦治疗的为ARB组,未使用的患者为DN组,泌尿外科行肾脏切除的患者为对照组(C组),收集各组患者血液检测血肌酐(Scr)、血尿素氮(BUN),留取尿液测24 h尿蛋白定量等临床指标;病理常规染色和特殊染色观察各组患者肾组织病理变化;免疫组化法检测各组患者肾组织TLR4及相关炎症因子表达水平。结果 DN组:血肌酐(235.8±21.8)μmol/L、血尿素氮(13.7±4.9)mmol/L、24 h尿蛋白定量(4.41±1.12)g;ARB组:血肌酐(217.7±22.7)μmol/L、血尿素氮(8.9±1.5)mmol/L、24 h尿蛋白定量(3.25±0.89)g;C组:血肌酐(51.6±29.6)μmol/L、血尿素氮(4.6±1.5)mmol/L、24 h尿蛋白定量(0.11±0.04)g;DN组均高于ARB组及C组(均P0.05)。病理染色结果显示:C组肾小球和肾小管未见明显变化;ARB组肾小球毛细血管球肥大,基底膜轻度增厚,系膜轻度增生,肾小管上皮细胞显示空泡和颗粒变性,肾间质和小动脉无明显病变;DN组肾小球毛细血管基底膜弥漫性增厚,系膜基质增生甚至有些肾小球的系膜基质重度增生,形成结节状硬化。免疫组化结果显示:TLR4、髓样分化因子88(MyD88)、核因子-κB(NF-κB)、单核细胞趋化因子(MCP-1)、肿瘤坏死因子(TNF-α)的表达,DN组较ARB、C组表达均增高(均P0.05),ARB组较C组表达增高(均P0.05)。TLR4与MyD88、NF-κB、MCP-1、TNF-α的表达量呈正相关(r分别为0.940、0.963、0.934、0.929,均P0.05)。结论糖尿病肾病患者体内TLR4信号通路被激活,使用厄贝沙坦可阻断TLR4信号通路,减轻患者肾功能损害,提示阻断TLR4信号通路可能成为治疗糖尿病肾病的新方法。
[Abstract]:Objective to investigate the relationship between Toll like receptor 4 (TLR4) signaling pathway and (DN) in diabetic nephropathy and the effect of angiotensin receptor antagonist (ARB) on TLR4 signaling pathway and the mechanism of renal protection. Methods from July 2012 to June 2014, diabetic nephropathy patients in Department of Nephrology, first affiliated Hospital of Nanchang University, ARB group treated with ARB irbesartan and DN group were treated with ARB irbesartan. The patients who underwent nephrectomy in urology were the control group (group C). The patients in each group were collected to detect serum creatinine (Scr),) blood urea nitrogen (BUN),) and urine samples for 24 h urine protein quantification. Pathological routine staining and special staining were used to observe the pathological changes of renal tissue in each group, and the expression of TLR4 and related inflammatory factors in renal tissue of each group were detected by immunohistochemical method. Results in DN group, serum creatinine was (235.8 卤21.8) 渭 mol/L, blood urea nitrogen was (13.7 卤4.9) mmol/L,24 h urinary protein quantification was (4.41 卤1.12) g. In ARB group, serum creatinine was (217.7 卤22.7) 渭 mol/L, blood urea nitrogen was (8.9 卤1.5) mmol/L,24 h urinary protein quantification was (3.25 卤0.89) g; In group C, serum creatinine (51.6 卤29.6) 渭 mol/L, blood urea nitrogen (4.6 卤1.5) mmol/L,24 / h urinary protein quantification (0.11 卤0.04) GDN were higher than those in ARB and C groups (P0.05). The results of pathological staining showed that there were no obvious changes in glomeruli and tubules in group C; In ARB group, glomerular capillary hypertrophy, slight thickening of basement membrane, slight proliferation of Mesangial membrane, vacuolation and granular degeneration of renal tubular epithelial cells, and no obvious changes in renal interstitial and arterioles were observed. In DN group, glomerular capillary basement membrane thickening, Mesangial matrix hyperplasia and some glomerular Mesangial matrix hyperplasia formed nodular sclerosis. The expression of TLR4, myeloid differentiation factor 88 (MyD88), nuclear factor- 魏 B (NF- 魏 B), monocyte chemokine (MCP-1) and tumor necrosis factor 伪) in DN group was higher than that in ARB, group. The expression of TNF- 伪 in group C was significantly higher than that in group C (P0.05). There was a positive correlation between the expression of TLR4 and MyD88,NF- 魏 Bmc-MCP-1TNF- 伪 (r = 0.940, 0.963, 0.934, 0.929, respectively, P0.05). Conclusion the TLR4 signal pathway is activated in diabetic nephropathy patients. Irbesartan can block the TLR4 signal pathway and alleviate the renal function damage in diabetic nephropathy patients. It suggests that blocking TLR4 signal pathway may be a new method for the treatment of diabetic nephropathy.
【作者单位】：南昌大学第一附属医院肾内科;
【基金】：国家自然科学基金资助项目(No.81060063;No.81100649;No.81660129) 江西省青年科学基金资助项目(No.20132BAB215004)
【分类号】：R587.2;R692.9

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