肾移植术后早期天然免疫分子Toll样受体4动态变化的规律

目的探讨天然免疫分子Toll样受体4（TLR4）在肾移植术后早期的动态变化规律及其在肾脏移植免疫中的作用。方法对18例肾移植术后早期病例进行了研究,采用三色标记流式细胞术检测肾移植术后第1、4、7天CD14阳性单核细胞中TLR4及其下游分子CD80的表达水平,同时观察患者术后恢复情况,根据术后2周内有无排斥反应将18例病例分为排斥组（3例）和无排斥组（15例）。对TLR4和CD80在排斥组和无排斥组的表达情况进行分析。结果（1）无排斥组肾移植术后第1、4、7天TLR4的表达水平呈下降趋势,分别为（21．38±16．02）％、（13．38±7．90）％和（4．28±3．74）％,术后第7天表达低于术后第1天和第4天表达,差异有统计学意义（均P〈0．05）;排斥组TLR4表达水平分别为（3．59±1．18）％、（21．5±20．54）％、（17．05±12．92）％,有不同程度升高（P〉0．05）。（2）排斥组（3例）术后第4天TLR4水平与术后第1天的环比（d4／d1）高于无排斥组（15例）,差异有统计学意义（P〈0．05）;排斥组（2例）术后第7天TLR4水平与术后第4天的环比（d7／d4）高于无排斥组（15例）,差异有统计学意义（P〈0．05）。排斥组1例术后第5天因移植肾急性排斥反应行移植肾切除术,术后第7天与第4天TLR4表达水平环比下降。（3）无排斥组肾移植术后第1、4、7天CD80的表达呈下降趋势,但差异无统计学意义（P〉0．05）。排斥组CD80的表达则有不同程度的升高,但差异无统计学意义（均P〉0．05）。结论肾移植术后早期TLR4的表达变化规律与患者免疫反应能力相一致;肾移植术后早期排斥组TLR4表达水平环比明显高于无排斥组。

Dynamics of expression of Toll-like receptor 4 early after renal transplantation: a clinical research

OBJECTIVE: To investigate the dynamics of expression of Toll-like receptor 4 (TLR4), an innate immune molecule, in patients early after renal transplantation and the role thereof in the renal transplantation immunity. METHODS: Eighteen patients early after renal transplantation were divided into rejection group (n = 3) and non-rejection group (n = 15) according to the rejection episode record within two weeks. 1, 4, and 7 days after transplantation peripheral blood samples were collected. Three-color fluorescent staining flow cytometry was used to detect the expression of TLR4 and CD80 in the CD14 positive monocytes. RESULTS: (1) The expression rates of TLR4 in the monocytes 1, 4, and 7 days after transplantation were (21.38 +/- 16.02)%, (11.81 +/- 8.49)% and (4.15 +/- 3.80)% respectively in the non-rejection group with a downtrend; and the expression rate of TLR4 at the 7th day was significantly lower than those at the 1st and 4th days (both P < 0.05); the expression rates of TLR4 in the monocytes 1, 4, and 7 days after transplantation were (3.59 +/- 1.18)%, (21.5 +/- 20.54)% and (17.05 +/- 12.92)% respectively in the rejection group, showing an increasing trend, however, without significant differences among any 2 values (all P > 0.05). (2) The link relative ratio of TLR4 expression of day 4 vs day 1 after renal transplantation in the rejection group was significantly higher than that in the non-rejection group (P < 0.05). The link relative ratio of TLR4 expression of the day 7 vs day 4 after renal transplantation in the rejection group was significantly higher than that in the non-rejection group (P < 0.05). One case of the rejection group underwent removal of the graft because of irreversible rejection at day 5 after renal transplantation, in which the TLR4 expression rate was decreased day 7. (3) In the non-rejection group, the expression of CD80 at the days 1, 4, and 7 after transplantation displayed a downtrend, however, without significant differences between any 2 values (all P > 0.05). In the rejection group, the expression of CD80 1, 4, and 7 days after transplantation were elevated in different degrees, however, without significant differences between any 2 values (all P > 0.05). CONCLUSION: The dynamics of expression of TLR4 in the patients early after renal transplantation is accordance with their immune state. The link relative ratio of TLR4 expression in the rejection group is significantly higher than that in the non-rejection group.