SDF-1/CXCR4在糖尿病肾组织中的表达及其与微血管异常的关系
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摘要
目的：观察基质细胞衍生因子-1(SDF-1)及其受体(CXCR4)在糖尿病鼠肾组织中的表达变化,并探讨与肾脏局部微血管异常的关系。
方法：将SD大鼠随机分为正常对照组(n=24)和糖尿病肾病组(n=24),构建链脲佐菌素(STZ)诱导的糖尿病肾病模型。采用免疫组化、实时定量聚合酶链反应(real-time PCR)方法,分别于8、12、20、28周,检测肾组织中SDF-1/CXCR4蛋白及mRNA表达水平,并与尿蛋白排泄、血管生成素(Angiopoietin,Ang)、内皮细胞标志物(CD133、TM-1)行相关性分析。
结果：(1)免疫组化显示正常对照组可见肾小管轻度SDF-1和CXCR4表达；糖尿病肾病组SDF-1/CXCR4明显上调(P<0.01),峰值均在20周,SDF-1主要在肾小管表达,于12周时小管间质也可见着染；CXCR4突出地表达于肾小管间质,20周时肾小管也明显染色。(2)正常对照组不同时点均有SDF-1α、CXCR4 mRNA的表达；糖尿病肾病组SDF-1αmRNA的表达仅在8周、28周时出现上调(P<0.05,P<0.01)；CXCR4 mRNA的表达与同时点正常对照组差异无统计学意义(p>0.05)。(3)糖尿病肾脏SDF-1和CXCR4蛋白表达呈显著的正相关(r=0.767, P<0.01); SDF-1或CXCR4的表达与尿蛋白排泄、Ang-2、CD133、TM-1表达水平明显相关。
结论：糖尿病大鼠肾组织存在SDF-1/CXCR4异常表达,且可能与肾脏局部微血管病变相关联；SDF-1/CXCR4的异常表达参与了糖尿病肾损害进程。
Objective:To observe the renal expressions of SDF-1 and CXCR4, and analyze its relationship with renal microvascular abnormalities in the kidney of diabetic rats.
Methods:The SD rats were divided into the diabetic group (n=24) and control group (n=24). The diabetic group was treated with a single intraperitoneal injection of streptozotocin (55mg/kg). The expression of SDF-1/CXCR4 in renal tissue were respectively detected by immunohisochemistry method and real-time polymerase chain reaction (real-time PCR) at 8,12,20 and 28 weeks. The relationship between SDF-1/CXCR4 and urinary protein, angiopoietin(Ang-1, Ang-2), endothelial cell markers (CD133, thrombomodulin-1) were analyzed.
Results:Compared with control group, the expression of SDF-1 and CXCR4 in diabetic kidney were significantly up-regulated after operation from 8 weeks to 28 weeks with the peak level at 20 weeks (P<0.01), and SDF-1/CXCR4 immunostaining were mainly found in renal tubular interstitium. SDF-1αand CXCR4 mRNA were detected at every time point in control group. The expression of SDF-1αmRNA in diabetic kidney was significantly up-regulated only at 8 and 28 weeks (P<0.05, P<0.01), but difference in expression of CXCR4 mRNA between the diabetic group and the control group was not found (P>0.05). The level of SDF-1 was positively correlated with CXCR4 (r=0.767, P<0.01). The level of SDF-1 or CXCR4 was positively correlated with urinary protein excretion, Ang-2, CD133 and TM-1 in diabetic group, respectively.
Conclusion:The abnormal expression of SDF-1/CXCR4 exist in the kidney of diabetic rats, and may be significantly associated with renal microvascular changes. The changes of SDF-1/CXCR4 is partly connected with the development of diabetic nephropathy.
方法：将SD大鼠随机分为正常对照组(n=24)和糖尿病肾病组(n=24),构建链脲佐菌素(STZ)诱导的糖尿病肾病模型。采用免疫组化、实时定量聚合酶链反应(real-time PCR)方法,分别于8、12、20、28周,检测肾组织中SDF-1/CXCR4蛋白及mRNA表达水平,并与尿蛋白排泄、血管生成素(Angiopoietin,Ang)、内皮细胞标志物(CD133、TM-1)行相关性分析。
结果：(1)免疫组化显示正常对照组可见肾小管轻度SDF-1和CXCR4表达；糖尿病肾病组SDF-1/CXCR4明显上调(P<0.01),峰值均在20周,SDF-1主要在肾小管表达,于12周时小管间质也可见着染；CXCR4突出地表达于肾小管间质,20周时肾小管也明显染色。(2)正常对照组不同时点均有SDF-1α、CXCR4 mRNA的表达；糖尿病肾病组SDF-1αmRNA的表达仅在8周、28周时出现上调(P<0.05,P<0.01)；CXCR4 mRNA的表达与同时点正常对照组差异无统计学意义(p>0.05)。(3)糖尿病肾脏SDF-1和CXCR4蛋白表达呈显著的正相关(r=0.767, P<0.01); SDF-1或CXCR4的表达与尿蛋白排泄、Ang-2、CD133、TM-1表达水平明显相关。
结论：糖尿病大鼠肾组织存在SDF-1/CXCR4异常表达,且可能与肾脏局部微血管病变相关联；SDF-1/CXCR4的异常表达参与了糖尿病肾损害进程。
Objective:To observe the renal expressions of SDF-1 and CXCR4, and analyze its relationship with renal microvascular abnormalities in the kidney of diabetic rats.
Methods:The SD rats were divided into the diabetic group (n=24) and control group (n=24). The diabetic group was treated with a single intraperitoneal injection of streptozotocin (55mg/kg). The expression of SDF-1/CXCR4 in renal tissue were respectively detected by immunohisochemistry method and real-time polymerase chain reaction (real-time PCR) at 8,12,20 and 28 weeks. The relationship between SDF-1/CXCR4 and urinary protein, angiopoietin(Ang-1, Ang-2), endothelial cell markers (CD133, thrombomodulin-1) were analyzed.
Results:Compared with control group, the expression of SDF-1 and CXCR4 in diabetic kidney were significantly up-regulated after operation from 8 weeks to 28 weeks with the peak level at 20 weeks (P<0.01), and SDF-1/CXCR4 immunostaining were mainly found in renal tubular interstitium. SDF-1αand CXCR4 mRNA were detected at every time point in control group. The expression of SDF-1αmRNA in diabetic kidney was significantly up-regulated only at 8 and 28 weeks (P<0.05, P<0.01), but difference in expression of CXCR4 mRNA between the diabetic group and the control group was not found (P>0.05). The level of SDF-1 was positively correlated with CXCR4 (r=0.767, P<0.01). The level of SDF-1 or CXCR4 was positively correlated with urinary protein excretion, Ang-2, CD133 and TM-1 in diabetic group, respectively.
Conclusion:The abnormal expression of SDF-1/CXCR4 exist in the kidney of diabetic rats, and may be significantly associated with renal microvascular changes. The changes of SDF-1/CXCR4 is partly connected with the development of diabetic nephropathy.
引文
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