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目的:研究转化生长因子β1(TGF-β1)在常染色体显性遗传性多囊肾病(ADPKD)患者中的表达分布特点,探讨其在ADPKD发病机制中的意义。方法:应用亲合素-生物素-过氧化物酶复合物(ABC)酶联免疫吸附法(ELISA)测定39例ADPKD患者的血浆、尿液及囊液中TGF-β1浓度;采用原位杂交和免疫组化方法检测TGF-β1、TGF-βⅠ型受体(TβRⅠ)、Ⅱ型受体(TβRⅡ)、结缔组织生长因子(CTGF)蛋白以及mRNA在正常肾及9例ADPKD患者肾组织中的表达分布特点,探讨其表达与肾间质纤维化程度的关系。结果:体液中血浆TGF-β1水平最高,ADPKD组为(15.12±8.53)μg/L、单纯性囊肿组为(11.43±8.93)μg/L,均显著高于正常对照组的(5.41±1.31)μg/L(P<0.05及P<0.01)。在ADPKD尿液中为(0.35±0.25)μg/(L.Cr)和囊液中为(0.31±0.21)μg/L,亦可检测出较低浓度的TGF-β1。在ADPKD患者肾组织中TGF-β1、TβRⅠ、TβRⅡ、CTGF蛋白及mRNA的表达较正常肾组织明显增加(P均<0.05),主要分布在萎缩的肾小管、间质血管周围及囊壁细胞。肾间质纤维化的程度与TGF-β1 mRNA(r=0.51,P=0.001)和蛋白(r=0.52,P=0.001)的阳性表达及CTGF mRNA(r=0.53,P=0.005)和蛋白(r=0.49,P=0.003)的阳性表达均呈明显正相关。结论:肾局部和循环中的TGF-β1在人ADPKD肾间质纤维化的进展中起一定作用。
Objective: To investigate the expression and distribution of transforming growth factor-β1 (TGF-β1) in patients with autosomal dominant polycystic kidney disease (ADPKD) and to explore its significance in the pathogenesis of ADPKD. Methods: The concentrations of TGF-β1 in plasma, urine and cystic fluid of 39 patients with ADPKD were determined by the method of avidin-biotin-peroxidase complex (ABC) enzyme-linked immunosorbent assay (ELISA) (TβRⅠ), type Ⅱ receptor (TβRⅡ), connective tissue growth factor (CTGF) protein and mRNA in normal kidney and 9 cases of ADPKD patients were detected by immunohistochemistry Expression and distribution of the relationship between the expression and the relationship between the degree of renal interstitial fibrosis. Results: The highest level of plasma TGF-β1 in body fluid was (15.12 ± 8.53) μg / L in ADPKD group and (11.43 ± 8.93) μg / L in simple cyst group, which was significantly higher than that in normal control group (5.41 ± 1.31) μg / L (P <0.05 and P <0.01). In ADPKD urine (0.35 ± 0.25) μg / (L.Cr) and cystic fluid (0.31 ± 0.21) μg / L, a lower concentration of TGF-β1 was also detected. The expression of TGF-β1, TβRⅠ, TβRⅡ, CTGF protein and mRNA in renal tissues of ADPKD patients were significantly higher than those in normal renal tissues (all P <0.05), mainly distributed in the atrophic renal tubules, interstitial blood vessels and cystic parietal cells. The degree of renal interstitial fibrosis was positively correlated with the expression of TGF-β1 mRNA (r = 0.51, P = 0.001) and protein (r = 0.52, r = 0.49, P = 0.003) were positively correlated with each other. CONCLUSIONS: TGF-β1, localized and circulating in the kidney, plays a role in the progression of renal interstitial fibrosis in human ADPKD.