IgA肾病患者肾组织Klotho蛋白与肾纤维化的关系

Relationship between Klotho protein and renal interstitial fibrosis in renal tissue of patients with IgA nephropathy

目的:观察Klotho蛋白及TGF-β蛋白在不同纤维化程度IgA肾病患者肾组织中的表达情况,探讨其与肾纤维化的关系。方法:选取肾活检确诊为IgA肾病患者,采用HE及Masson染色检测肾小管损伤及间质纤维化程度来评估肾纤维化的程度,随机选取不同肾纤维化程度患者69例,肾透明细胞癌患者癌旁正常肾组织20例,按纤维化程度分组:正常对照组、纤维化Ⅰ级、纤维化Ⅱ级、纤维化Ⅲ级,采用免疫组织化学技术检测Klotho蛋白及TGF-β蛋白的表达情况,探讨Klotho蛋白及TGF-β蛋白与肾纤维化的关系。结果:随着肾脏病理损害明显,肾组织Klotho蛋白表达量逐渐减少,差异有统计学意义(P<0.05),TGF-β蛋白表达量逐渐增加,差异有统计学意义(P<0.05);线性相关分析显示,肾组织Klotho水平与eGFR、Ca、Hb呈正相关,与TGF-β、年龄、Scr、Cys c、P呈负相关;多元线性回归分析显示,年龄、TGF-β、Ca、P,均是影响Klotho水平的因素。结论:Klotho蛋白水平随着肾纤维化加重而逐渐降低,Klotho不仅有望成为预测肾纤维化的生物标志物,还极具希望成为肾脏疾病诊断的早期标志物及干预肾脏纤维化的靶点。

Objective To observe the expression of Klotho protein and TGF-βprotein in renal tissues of patients with different degrees of fibrotic IgA nephropathy,and to explore its relationship with renal interstitial fibrosis.Method Patients with IgA nephropathy diagnosed by renal biopsy were enrolled.Assessment of renal fibrosis by HE and Masson staining for detection of tubular damage and interstitial fibrosis.Randomized selection of 69 patients with different degrees of renal fibrosis,and 20 patients with normal renal tissue adjacent to renal clear cell carcinoma were included.According to the degree of fibrosis:normal control group,fibrosis gradeⅠ,fibrosis gradeⅡ,fibrosis gradeⅢ,detection of Klotho protein by immunohistochemistry and the expression of TGF-βprotein,to explore the relationship between Klotho protein and TGF-βprotein and renal fibrosis.Results With the obvious pathological damage of kidney,the expression of Klotho protein in renal tissue decreased gradually(P<0.05),and the expression of TGF-βprotein increased gradually(P<0.05).Linear correlation analysis showed that Klotho level in kidney tissue and eGFR,Ca,Hb Positive correlation,negative correlation with TGF-β,age,Scr,Cys c,P;multiple linear regression analysis showed that age,TGF-β,Ca,P,are factors influencing Klotho levels.Conclusion Klotho protein level gradually decreases with the increase of renal fibrosis.Klotho is not only a biomarker for predicting renal fibrosis,but also promising as an early marker for the diagnosis of kidney disease and a target for intervention in renal fibrosis.