益肾活血法干预小儿原发性肾病综合征对NGAL、KIM-1、IL-18的影响

发布时间：2018-05-19 06:30

本文选题：小儿原发性肾病综合征 + 中性粒细胞明胶酶相关脂质运载蛋白　；参考：《福建中医药大学》2017年硕士论文

【摘要】：目的:应用益肾活血中药肾康灵干预儿童频复发性肾病(frequent relapse nephrotic syndrome,FRNS),通过观察FRNS患儿治疗前后尿中性粒细胞明胶酶相关性脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、肾损伤分子 1(kidney injury molecule 1,KIM-1)、白细胞介素18(interleukin 18,IL-18)等变化,进一步阐明小儿FRNS的发病机制及益肾活血中药肾康灵干预小儿FRNS的作用机制,寻找肾脏早期损害的生物学标记物,以提高FRNS的临床疗效。方法:选自2016年1月至2016年12月期间福建中医药大学附属人民医院及福州军区总医院门诊和住院FRNS(单纯型、频复发)患儿40例,采用随机数字表法分为中西医结合治疗组20例(A组)和西药对照组20例(B组),从体检中心抽取健康儿童20例作为健康对照组(C组)。观察两组治疗前和治疗4周后、12周后的尿NGAL、KIM-1、IL-18变化。应用SPSS20.0软件进行统计学处理。结果:1.治疗前比较,A、B两组的尿NGAL、KIM-1、IL-18水平明显高于C组(P均0.01),而AB两组间的尿NGAL、KIM-1、IL-18、α1微球蛋白水平和血清蛋白、胆固醇、甘油三酯、肌酐水平比较无显著差异(P均0.05)。2.治疗4周后,与治疗前比较A、B两组尿的NGAL、KIM-1、IL-18、α1微球蛋白水平明显降低(P均0.01),血清白蛋白明显升高(P0.01),血肌酐无显著变化(P均0.05),血清胆固醇、甘油三酯A组降低(P0.01和P0.05),而B组无显著差异(P0.05);A组与B组比较,A组的尿KIM-1水平明显低于B组(P0.01),尿NGAL水平明显高于B组(P0.01),尿IL-18、α1微球蛋白水平A、B两组比较无显著差异(P均0.05),胆固醇、甘油三酯水平A组明显低于B组(P均0.05),血清蛋白水平A组明显高于B组(P0.05),血肌酐A、B两组间无显著差异(P0.05)。3.治疗12周后,与治疗前比较A、B两组尿NGAL、KIM-1、IL-18、α1微球蛋白、血清胆固醇、甘油三酯水平明显降低(P均0.01),血清白蛋白明显升高(P均0.01),血肌酐无显著变化(P均0.05);与治疗4周后比较,尿NGAL水平A组明显降低(P0.01),而B组比较无显著差异(P0.05),尿KIM-1、IL-18、α1微球蛋白、血清胆固醇、甘油三酯水平明显降低(P0.01,P0.01,P0.01,P0.05,P0.05),血清白蛋白明显升高(P0.01),血肌酐无显著变化(P0.05);A组与B组比较,尿NGAL、KIM-1、IL-18、α1微球蛋白、血肌酐水平无显著差异(P均0.05),血清蛋白水平A组明显高于B组(P0.05),胆固醇、甘油三酯水平A组明显低于B组(P0.05和P0.01)。尿NGAL、KIM-1、IL-18的ROC曲线下面积分别为0.893、0.886、0.837,最佳临界点分别为 84.78ng/ml、8.01ng/ml、212.56pg/ml,敏感性分别为 87%、74%、87%,特异性分别为 82%、91%、73%。结论:①FRNS患儿存在着尿NGAL、KIM-1、IL-18水平的异常升高,提示NGAL、KIM-1、IL-18参与了 FRNS的发病机制。②应用益肾活血中药肾康灵治疗后KIM-1下降明显,治疗4周后治疗组指标水平低于对照组,中药肾康灵可能对降低患儿尿NGAL、IL-18水平有一定作用,中药结合西药治疗,可能有助于减轻肾小管损伤的程度。③中西医结合治疗在提高血清白蛋白,降低胆固醇、甘油三酯等疗效方面优于单纯西药组,中药肾康灵能通过改善体内高凝、高脂状态,提高临床疗效。④尿NGAL、KIM-1、IL-18较血肌酐变化更敏感,在血肌酐未发生改变之前尿NGAL、KIM-1、IL-18就发生改变,因此,尿NGAL、KIM-1、IL-18可作为肾小管早期损害的特异性生物学标记物,为FRNS的临床治疗和预后判断提供客观指标。
[Abstract]:Objective: to use Yishen and blood activating medicine Shen Kang Ling to interfere with Frequent Relapse Nephrotic Syndrome (FRNS), and to observe the urinary neutrophil gelatinase related lipid carrier protein (neutrophil gelatinase-associated lipocalin, NGAL), kidney injury molecule 1 (kidney injury) 1, before and after treatment of children with FRNS. ), the changes of interleukin 18 (interleukin 18, IL-18) and so on, further elucidate the pathogenesis of FRNS in children and the mechanism of Shen Kang Ling to intervene in children's FRNS, look for the biological markers of early renal damage to improve the clinical efficacy of FRNS. Methods: from January 2016 to December 2016, the Fujian University of traditional Chinese medicine was attached. 40 cases of FRNS (Dan Chunxing, frequency recurrent) children in the people's Hospital and the General Hospital of the Fuzhou military area general hospital were divided into 20 cases (group A) and 20 cases (group B) with western medicine combined treatment group and Western medicine control group. 20 healthy children were selected from the medical center as the healthy control group (group C). The two groups were observed before and after 4 weeks of treatment and 12 weeks later. The urine NGAL, KIM-1, IL-18 changes. The results were as follows: 1. before treatment, the levels of NGAL, KIM-1, IL-18 in group A and B two were significantly higher than those of C group (P 0.01), while there was no significant difference in the level of alpha 1 microglobulin and serum protein, cholesterol, triglyceride and creatinine in the two groups of AB (0.05 After 4 weeks of.2. treatment, compared with before treatment, the levels of NGAL, KIM-1, IL-18, and alpha 1 microglobulin in the urine of B two were significantly decreased (P 0.01), serum albumin increased significantly (P0.01), serum creatinine was not significantly changed (P 0.05), serum cholesterol and triglyceride A group decreased (P0.01 and P0.05), but there was no significant difference in the group (P0.01 and P0.05). The level of urine NGAL was significantly lower than that of group B (P0.01), the level of urine NGAL was higher than that of group B (P0.01), the level of IL-18, alpha 1 microglobulin level A, B two group was no significant difference (P 0.05), the cholesterol and triglyceride level in A group was significantly lower than that of B group (P all 0.05), serum creatinine levels were significantly higher than those of the group two. After the week, the urine NGAL, KIM-1, IL-18, alpha 1 microglobulin, serum cholesterol and triglyceride levels were significantly decreased (P 0.01), serum albumin was significantly increased (P 0.01), serum creatinine was not significantly changed (P 0.05) in the two groups of B two, and the serum albumin was significantly lower (P0.01) compared with the 4 weeks after treatment (P0.01), but there was no significant difference between the B group and the urine. KIM-1, IL-18, alpha 1 microglobulin, serum cholesterol and triglyceride levels decreased significantly (P0.01, P0.01, P0.01, P0.05, P0.05), serum albumin increased significantly (P0.01), and serum creatinine was not significantly changed (P0.05). There was no significant difference between A and B group. There was no significant difference in the level of urinary NGAL, 1 microglobulin and serum creatinine (0.05), and the serum albumin level was significantly higher. In group B (P0.05), the level of cholesterol and triglyceride level in A group was significantly lower than that in group B (P0.05 and P0.01). The area under the ROC curve of NGAL, KIM-1 and IL-18 was 0.893,0.886,0.837, and the best critical point was 84.78ng/ml, respectively, and the sensitivity was 87%, 74%, 87% respectively, and the specificity was 82%, 91% respectively. The abnormal elevation of GAL, KIM-1 and IL-18 levels suggested that NGAL, KIM-1 and IL-18 were involved in the pathogenesis of FRNS. (2) the decrease of KIM-1 in the treatment group was obviously lower after the treatment of Yishen Huoxue Chinese medicine Shen Kang Ling. After 4 weeks of treatment, the index level of the treatment group was lower than that of the control group. The combination of Chinese and Western medicine is better than the western medicine group in improving serum albumin, lowering cholesterol and triglyceride. The Chinese medicine Shen Kang Ling can improve the body hypercoagulability, high fat state and improve the clinical effect. 4. The urine NGAL, KIM-1, IL-18 are more sensitive than the blood creatinine, and in the blood creatinine The urine NGAL, KIM-1, and IL-18 changes before the changes. Therefore, urine NGAL, KIM-1, and IL-18 can be used as specific biomarkers for the early damage of renal tubules, providing an objective indicator for the clinical treatment and prognosis of FRNS.
【学位授予单位】：福建中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R272

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