阿奇霉素对多柔比星肾病大鼠血清白细胞介素-23、白细胞介素-17的影响

Effect of Azithromycin on the level of interleukin - 23, interleukin - 17 in serum of rats with Adriamycin - induced nephrosis

目的通过观察多柔比星肾病大鼠血清白细胞介素（IL）-23、IL-17水平的变化，探讨阿奇霉素（AZM）通过IL-23／IL-17轴在多柔比星肾病免疫机制中的作用。方法将135只大鼠按随机数字表法分为对照组、模型组、AZM干预组、泼尼松干预组和联合干预组。采用2次尾静脉注射多柔比星建立肾病模型，分别于4、6、8周每组随机抽取9只大鼠检测血、尿生化指标，采用酶联免疫吸附实验观察血清IL-23、IL-17水平的变化。结果8周时，与模型组相比，3个干预组24h尿蛋白定量[模型组（354．83±70．87）mg／d，AZM干预组（94．59±22．67）mg／d，泼尼松干预组（65．64±8．71）mg／d，联合干预组（47．44±9．56）mg／d]、总胆固醇[模型组（8．71±1．60）mmol／L，AZM干预组（3．54±0．30）mmol／L，泼尼松干预组（3．10±0．18）mmol／L，联合干预组（2．56±0．40）mmo]／L]明显下降，清蛋白[模型组（16．77±3．15）g/L，AZM干预组（33．82±1．16）g/L，泼尼松干预组（37．80±2．73）g／L，联合干预组（40．78±2．63）g／L]明显上升，差异均有统计学意义（F=152．243、99．838、155．836，P均〈0．05）。4周时，模型组和3个干预组血清IL-23水平[模型组（29．60±3．97）ng／L，AZM干预组（29．61±2．62）ng／L，泼尼松干预组（29．74±2．23）ng／L，联合干预组（30．31±2．20）ng／L]、IL-17水平[模型组（22．38±2．51）ng／L，AZM干预组（21．97±1．89）ng／L，泼尼松干预组（21．43±2．42）ng／L，联合干预组（21．51±2．07）ng／L]显著高于对照组[（17．35±3．01）ng／L、（14．03±2．42）ng／L]，差异均有统计学意义（F=33．819、21．373，P均〈0．05）；第6周、8周时3个干预组血清IL-23水平[第6周AZM干预组（27．20±1．71）ng／L，泼尼松干预组（24．39±2．06）ng／L，联合干预组（21．41±1．71）ng／L；第8周AZM干预组（24．60-1-2．91）ng／L，泼尼松干预组（21．01±1．02）ng／L，联合干预组（18．93±1．35）ng／L]、IL-17水平[第6周AZM干预组（19．12±0．37）ng／L，泼尼松干预组（18．54±0．36）ng／L，联合干预组（17．57±0．42）ng／L；第8周AZM干预组（17．44±0．46）ng／L，泼尼松干预组（16．37±0．49）ng／L，联合干预组（14．71±0．99）ng／L]低于模型组[第6周IL-23（35．78±3．21）ng／L，第8周IL-23（44．47±7．84）ng／L，第6周IL-17（26．69±3．70）ng／L，第8周IL-17（34．03±3．45）ng／L]，差异均有统计学意义（第6周F=82．963、44．659，第8周F=75．085、200．383，P均〈0．05）；泼尼松干预组IL-23、IL-17水平低于AZM干预组（P〈0．05），联合干预组IL-23、IL-17水平的下降与单独干预组相比差异有统计学意义（P〈0．05）。结论IL-23／IL-17轴的高活动性可能是多柔比星肾病免疫机制之一。AZM可能通过抑制IL-23／IL-17轴的高活动性对多柔比星肾病起缓解作用。AZM对IL-23／IL-17轴具有类似于糖皮质激素的抑制作用，并有增强泼尼松的作用。

Objective To explore the effect of Azithromycin on the immune mechanisms through the IL -23/ IL - 17 axis way by observing the changes in serum levels of IL - 23, IL - 17 in rats with Adriamyein - induced nephro- sis. Methods A total of 135 rats were randomly divided into control group, model group, Azithromycin intervention group, Prednisone intervention group and united intervention group. The model was induced through a tail intravenous injection of Adriamycin for 2 times. Nine rats were randomly selected from every group to detect blood and urinary bio- chemistry,and to observe the changes of the serum levels of IL- 23, IL- 17 by enzyme -linked immunosorbent assay in 4,6, and 8 weeks. Results Compared with the model group in the 8th week, the levels of 24 - hour urinary protein [ model group （ 354.83 ± 70.87 ） mg/d, Azithromycin intervention group （ 94.59 ± 22.67 ） mg/d, Prenisone intervention group（ 65.64 ± 8.71 ） mg/d, united intervention group （ 47.44 ± 9.56 ） mg/d ] , cholesterol [ model group （ 8.71 ± 1.60 ） mmol/L, Azithromyein intervention group （ 3.54 ± 0.30 ） mmol/L, Prenisone intervention group （ 3.10 ± 0.18 ） mmol/L, united intervention group （ 2.56 ± 0.40 ） mmol/L ] were reduced significantly, while the levels of albumin [ model group （ 16.77 ± 3.15 ） g/L, Azithromyein intervention group （33.82 ± 1.16 ） g/L, Prenisone intervention group （37.80 ±2. 73 ） g/L, united intervention group（40.78 ± 2.63 ） g/L] were increased obviously in the intervention groups, and the differences were statistically significant （ F = 152. 243,99. 838,155. 836, all P 〈 0.05 ）. The serum levels of IL - 23 [ model group （ 29.60 ± 3.97 ） ng/L, Azithromyein intervention group （29.61 ± 2.62 ） ng/L, Prenisoneintervention group（29.74 ± 2.23 ） ng/L, united intervention group （ 30.31 ± 2.20） ng/L 1 , IL - 17 [ model group （22.38 ±2.51 ） ng/L,Azithromycin intervention group（21.97 ± 1.89） ng/L,Prenisone intervention group（21.43 ± 2.42） ng/L,united intervention group（21.51 ±2.07） ng/L] in the model group and 3 intervention groups were higher than the control group[ （ 17.35 ± 3.01 ） ng/L, （ 14.03 ± 2.42） ng/L] in the 4th week, and there were significant differences （ F = 33. 819,21. 373, all P 〈 0.05 ） ; and the levels of IL - 23 [ in the 6th week, Azithromycin intervention group（27.20 ± 1.71 ） ng/L, Prenisone intervention group （ 24.39 ± 2.06 ） ng/L, united intervention group （ 21.41 ± 1.71 ） ng/L, model group （ 35.78 ± 3.21 ） ng/L; in the 8th week, Azithromycin intervention group （ 24.60 ± 2.91 ） ng/L, Prenisone intervention group（ 21.01 ± 1.02 ） ng/L, united intervention group（ 18.93 ± 1.35 ） ng/L, model group （44.47 ± 7.84 ） ng/L] , IL - 17 [in the 6th week, Azithromyein intervention group （ 19.12 ± 0.37 ） ng/L, Prenidone in- tervention group（ 18.54 ± 0. 36 ） ng/L, united intervention group （ 17.57 ± 0.42 ） ng/L, model group （ 26.69 ± 3.70 ） ng/L ;in the 8th week, Azithromyein intervention group （ 17.44 ± 0.46 ） ng/L, Prenidone intervention group （ 16.37 ± 0. 49 ） ng/L,united intervention group（ 14.71 ± 0.99） ng/L, model group（34.03 ± 3.45 ） ng/L] in the 3 intervention groups were significantly lower than those of the model group in the 6th ,8th week（ F = 82. 963,44. 659 in the 6th week, F =75. 085,200.383 in the 8th week, all P 〈 0.05 ）. The levels of 1L - 23, IL - 17 in united intervention group were lower than those in respective intervention groups （P 〈 0.05 ） , and the levels in Prednisone intervention group were lower than those in Azithromyein intervention group（ P 〈 0.05 ）. Conclusions IL - 23/IL - 17 axis＇ high activity may be one of the immunologic mechanisms of Adriamycin - induced nephrosis. Azithromycin may inhibit the high activity of IL - 23/IL - 17 axis to relieve the Adriamyciu - induced nephrosis. The inhibition on IL - 23/IL - 17 axis of Azithro- myein was similar to Prednisone,and Azithromycin may enhance the etteetiveness of Prednisone.