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继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)是慢性肾脏病病人最常见的严重并发症之一[1],在透析病人中SHPT的发病率可高达50%,且严重影响透析病人的生活质量和生存率[2]。目前对SHPT的发病机制、疾病进展影响因素及预后等方面的研究尚不深入,需进一步研究。越来越多的证据支持慢性炎症是导致细胞增生和肿瘤发生、进展的确切因素之一,NOD样受体家族蛋白3(NOD-like receptor family pyrin domain containing 3, NLRP3)炎性小体是目前研究最为深入且在多种细胞中表达的炎性体[3],其在细胞增生及肿瘤发生、发展等方面的起到一定作用,但NLRP3在SHPT中的作用尚未阐明。本研究旨在探讨NLRP3在SHPT中的表达情况,并分析其与SHPT临床病理特征的关系。现作报道。
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88例SHPT病人中男54例,女34例;年龄30~73岁,中位年龄50岁;血液透析75例,腹膜透析4例,血液透析联合腹膜透析9例;透析龄1~16年,平均8年,其中≤5年21例,>5~ < 10年36例,≥10年31例。
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HE染色切片显示,正常的甲状旁腺腺细胞排列成索团状,其间富含有孔毛细血管及少量结缔组织,还可见较多的脂肪细胞(见图 1);SHPT病人甲状旁腺中主细胞和嗜酸性细胞普遍体积变大,排列成弥漫性的实性片状(见图 2),或者呈结节、梁状、滤泡状、腺泡样形态,也可以呈菊形团样、乳头状,常见的是不同排列形态混合形成腺瘤样增生,间质内仅见少量脂肪细胞,周围有纤维结缔组织分隔(见图 3)。
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88例SHPT病人的术前血清NLRP3的表达水平为(290.66±72.53),明显高于健康体检人群的血清NLRP3的水平(75.59±20.05)(t′=22.86,P < 0.01)。
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检测88例SHPT病人的甲状旁腺组织和10例因甲状腺疾病行甲状腺全切手术时带有正常甲状旁腺且无肾脏病者的甲状旁腺组织,结果NLRP3蛋白在正常甲状旁腺组织中的阳性率为20.00%,且为弱阳性(见图 4),NLRP3蛋白在SHPT病人的甲状旁腺组织中的阳性率为95.45%,表现为不同程度的阳性(见图 5~7)。NLRP3蛋白在SHPT病人异常增生的甲状旁腺组织中的表达率显著高于正常甲状旁腺组织(P < 0.01)(见表 1)。不同性别、年龄、透析方式、透析龄等SHPT病人甲状旁腺组织中NLRP3蛋白表达差异均无统计学意义(P>0.05)(见表 2)。
分组 n NLRP3 Z P - + 2+ 3+ 增生的甲状旁腺组织 88 4 10 39 35 正常的甲状旁腺组织 10 8 2 0 0 5.06 < 0.01 合计 98 12 12 39 35 表 1 NLRP3在正常甲状旁腺组织及SHPT病人的甲状旁腺组织中的表达
临床病理参数 n NLRP3 Z P - + 2+ 3+ 性别 男 54 2 7 22 23 0.46 >0.05 女 34 2 3 17 12 年龄/岁 < 50 42 1 6 16 19 0.76 >0.05 ≥50 46 3 4 23 16 透析方式 血液透析 75 4 8 34 29 腹膜透析 4 0 1 2 1 1.30* >0.05 血液透析联合腹膜透析 9 0 1 3 5 透析龄/年 ≤5 21 2 4 9 6 >5~ < 10 36 0 3 18 15 2.91 >0.05 ≥10 31 2 3 12 14 *示χ2值 表 2 不同临床参数SHPT病人甲状旁腺组织中NLRP3蛋白表达
NLRP3在继发性甲状旁腺功能亢进症中的表达及临床意义
Expression of NLRP3 in secondary hyperparathyroidism and its clinical significance
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摘要:
目的探讨NOD样受体家族蛋白3(NLRP3)炎性小体在慢性肾脏病继发性甲状旁腺功能亢进症(SHPT)中的表达及临床意义。 方法应用HE染色观察SHPT病人异常增生的甲状旁腺镜下形态;采用ELISA法检测正常人和SHPT病人血清中NLRP3水平;免疫组织化学SP法检测NLRP3在正常和异常增生的甲状旁腺组织中的表达,并分析NLRP3的表达与SHPT临床病理特征的关系。 结果SHPT病人异常增生的甲状旁腺镜下可表现为弥漫性及腺瘤样增生,与正常甲状旁腺表现明显不同;NLRP3在SHPT病人血清中的水平明显高于正常人(P < 0.01);NLRP3在SHPT病人异常增生的甲状旁腺组织中的阳性率明显高于正常甲状旁腺组织(P < 0.01)。不同性别、年龄、透析方式、透析龄等SHPT病人甲状旁腺组织中NLRP3蛋白表达差异均无统计学意义(P>0.05)。 结论NLRP3可能参与慢性肾脏病病人SHPT的发生、发展,其高表达有望成为SHPT早期诊断及预后评估的重要指标。 -
关键词:
- 继发性甲状旁腺功能亢进症 /
- 慢性肾脏病 /
- NOD样受体家族蛋白3
Abstract:ObjectiveTo investigate the expression and clinical significance of NOD-like receptor family pyrin domain containing 3(NLRP3) in secondary hyperparathyroidism(SHPT). MethodsHE staining was used to observe the difference of parathyroid gland in normal people and SHPT patients.ELISA was used to detect the serum level of NLRP3 in normal people and SHPT patients.Immunohistochemistry of SP method was used to detect the expression of NLRP3 in normal and hyperplastic parathyroid tissue, and the relationship between NLRP3 expression and SHPT clinical-pathological characteristics was analyzed. ResultsHyperplastic parathyroid glands in SHPT patients manifested as diffuse and adenoma-like hyperplasia, which was obviously different from that of normal, and the serum level of NLRP3 in SHPT patients was significantly higher than that of normal people(P < 0.01).The positive rate of NLRP3 in abnormal hyperplastic parathyroid tissue in SHPT patients was significantly higher than that in normal parathyroid tissue(P < 0.01).The expression of NLRP3 in SHPT patients had no correlation with gender, age, dialysis method or dialysis age(P>0.05). ConclusionsNLRP3 may be involved in the occurrence and development of SHPT, and its high expression is expected to become an important indicator for the early diagnosis and prognostic evaluation of SHPT. -
表 1 NLRP3在正常甲状旁腺组织及SHPT病人的甲状旁腺组织中的表达
分组 n NLRP3 Z P - + 2+ 3+ 增生的甲状旁腺组织 88 4 10 39 35 正常的甲状旁腺组织 10 8 2 0 0 5.06 < 0.01 合计 98 12 12 39 35 表 2 不同临床参数SHPT病人甲状旁腺组织中NLRP3蛋白表达
临床病理参数 n NLRP3 Z P - + 2+ 3+ 性别 男 54 2 7 22 23 0.46 >0.05 女 34 2 3 17 12 年龄/岁 < 50 42 1 6 16 19 0.76 >0.05 ≥50 46 3 4 23 16 透析方式 血液透析 75 4 8 34 29 腹膜透析 4 0 1 2 1 1.30* >0.05 血液透析联合腹膜透析 9 0 1 3 5 透析龄/年 ≤5 21 2 4 9 6 >5~ < 10 36 0 3 18 15 2.91 >0.05 ≥10 31 2 3 12 14 *示χ2值 -
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