血清Klotho水平与早期糖尿病肾病足细胞损伤的相关研究
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摘要
目的:观察早期糖尿病肾病(DN)患者血清Klotho水平与足细胞损伤的相关性。方法:选取2018年01月～2018年10月入住本院明确诊断为2型糖尿病的患者60例,依据其尿白蛋白肌酐比值(UACR)分为正常蛋白尿组、微量白蛋白尿组,每组30例,同时选取同期健康体检者30例作为对照组,采用RT-PCR法检测各组血清Klotho、Nephrin和Podocin mRNA水平,分析血清Klotho与足细胞损伤的相关性。结果:正常蛋白尿组和微量白蛋白尿组患者血清Klotho、Nephrin及Podocin mRNA水平均低于对照组,差异均有统计学意义(均P <0. 01);而与正常蛋白尿组比较,微量白蛋白尿组患者血清Klotho、Nephrin、Podocin mRNA水平也均明显降低,差异均有统计学意义(分别为P <0. 05、P <0. 05和P <0. 01);进一步Pearson相关分析显示,血清Klotho水平与Nephrin、Podocin均呈正相关;多元回归分析显示,早期DN患者血清Klotho水平与Nephrin关系密切。结论:早期DN患者血清Klotho水平降低可能参与了足细胞损伤。
Objective: To investigate the levels of serum Klotho levels in the patients witn early diabetic nephropathy,and analysis the relationship between Klotho and podocyte injury. Methods: 60 patients with type 2 diabetes diagnosed in our hospital from January to October 2018 were enrolled. According to their urinary albumin creatinine ratio( UACR),they were divided into normal proteinuria group and microalbuminuria group. Meanwhile,30 healthy subjects in the same period were selected as the control group.The levels of serum Klotho mRNA were detected by real-time PCR and the podocyte injury was analyzed. Results: Compared with the control group,the serum Klotho、Nephrin and Podocin mRNA levels in the normal proteinuria group and microalbuminuria group,the differences were statistically significant( each P < 0. 01); and Compared with the normal proteinuria group,the levels of serum Klotho、Nephrin、Podocin mRNA in the microalbuminuria group were significantly decreased,the differences were also statistically significant( respectively P < 0. 05,P < 0. 05 and P < 0. 01). Correlation analysis showed that serum Klotho was positively correlated with Nephrin and Podocin levels. Multiple linear regression analysis also showed that serum Klotho was closely related to Nephrin in early diabetic nephropathy patients. Conclusion: Serum Klotho reducing maybe associates with podocyte injury in early diabetic nephropathy.
Objective: To investigate the levels of serum Klotho levels in the patients witn early diabetic nephropathy,and analysis the relationship between Klotho and podocyte injury. Methods: 60 patients with type 2 diabetes diagnosed in our hospital from January to October 2018 were enrolled. According to their urinary albumin creatinine ratio( UACR),they were divided into normal proteinuria group and microalbuminuria group. Meanwhile,30 healthy subjects in the same period were selected as the control group.The levels of serum Klotho mRNA were detected by real-time PCR and the podocyte injury was analyzed. Results: Compared with the control group,the serum Klotho、Nephrin and Podocin mRNA levels in the normal proteinuria group and microalbuminuria group,the differences were statistically significant( each P < 0. 01); and Compared with the normal proteinuria group,the levels of serum Klotho、Nephrin、Podocin mRNA in the microalbuminuria group were significantly decreased,the differences were also statistically significant( respectively P < 0. 05,P < 0. 05 and P < 0. 01). Correlation analysis showed that serum Klotho was positively correlated with Nephrin and Podocin levels. Multiple linear regression analysis also showed that serum Klotho was closely related to Nephrin in early diabetic nephropathy patients. Conclusion: Serum Klotho reducing maybe associates with podocyte injury in early diabetic nephropathy.
引文
1. Mallipattu SK,He JC. Podocyte as a direct target for treatment of glomerular disease. Am J Physiol Renal Physiol,2016,311(1):F46-F51.
2 . Kuro-o M,Matsumura Y,Aizawa H,et al. Mutation of the mouse Klotho gene leads to a syndrome resembling ageing Nature,1997,390(6655):45-51.
3 . Karalliedde J,Maltese G,Hill B,et al. Effect of renin-angiotensin system blockade on soluble Klotho in patients with type 2 diabetes,systolic hypertension,and albuminuria. Clin Jam Soc Nephrol,2013,8(11):1899-1905.
4 . Fountoulakis N,Maltese G,Gnudi L,et al. Reduced levels of anti-ageing hormone klotho predict renal function decline in Type 2Diabetes,2018,103(5):2026-2032.
5 . Nie F,Wu D,Du H,et al. Serum klotho protein level and their correlations with the progression of type 2 diabetes mellitus. J Diabetes complications,2017,31(3):594-598.
6 . Kim SS,Song SH,Kim IJ,et al. Decreased plasmaα-Klotho predict progression of nephropathy with type 2 diabetic patients.J Diabetes complications,2016,30(5):887-892.
7 . Kim JH,Xie J,Hwang KH,Wu YL,et al. Klotho may ameliorate proteinuria by targeting TRPC6 channels in podocytes. J Am Soc Nephrol,2017,28(1):140-151.
8 . Rotondi S,Pasquali M,Tartaglione L,et al. Soluble alphaKlotho serum levels in chronic kidney disease. Int J Endocrinol,2015,2015:872193.
2 . Kuro-o M,Matsumura Y,Aizawa H,et al. Mutation of the mouse Klotho gene leads to a syndrome resembling ageing Nature,1997,390(6655):45-51.
3 . Karalliedde J,Maltese G,Hill B,et al. Effect of renin-angiotensin system blockade on soluble Klotho in patients with type 2 diabetes,systolic hypertension,and albuminuria. Clin Jam Soc Nephrol,2013,8(11):1899-1905.
4 . Fountoulakis N,Maltese G,Gnudi L,et al. Reduced levels of anti-ageing hormone klotho predict renal function decline in Type 2Diabetes,2018,103(5):2026-2032.
5 . Nie F,Wu D,Du H,et al. Serum klotho protein level and their correlations with the progression of type 2 diabetes mellitus. J Diabetes complications,2017,31(3):594-598.
6 . Kim SS,Song SH,Kim IJ,et al. Decreased plasmaα-Klotho predict progression of nephropathy with type 2 diabetic patients.J Diabetes complications,2016,30(5):887-892.
7 . Kim JH,Xie J,Hwang KH,Wu YL,et al. Klotho may ameliorate proteinuria by targeting TRPC6 channels in podocytes. J Am Soc Nephrol,2017,28(1):140-151.
8 . Rotondi S,Pasquali M,Tartaglione L,et al. Soluble alphaKlotho serum levels in chronic kidney disease. Int J Endocrinol,2015,2015:872193.