T细胞亚群与CD4~+ CD25~+调节性T细胞及Foxp3 mRNA在肾移植大鼠急性排斥反应中的作用

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目的探讨大鼠肾移植术后急性排斥反应中外周血T淋巴细胞亚群、CD4~+CD25~+调节性T细胞比率和叉头状转录因子p3(forkhead transcription factor p3,Foxp3)mRNA表达水平及意义。方法 SD大鼠15只为对照组;SD大鼠15只为受体、SD大鼠15只为供体建立同系基因移植非急性排斥组;SD大鼠15只为受体、Wistar大鼠15只为供体建立非同系基因移植急性排斥组。于肾移植术后第7天检测3组受体大鼠外周血T淋巴细胞亚群、CD4~+CD25~+调节性T细胞比率、Foxp3 mRNA水平及血清肌酐、尿素氮水平,对移植肾行组织病理学检査并进行肾移植急性排斥反应分级,并进行比较。结果肾脏组织病理显示,对照组大鼠无明显病理变化;非急性排斥组4只受体大鼠呈现交界性改变,小灶状间质炎性细胞浸润,3只出现急性排斥反应Ⅰ级病变,其余8只受体大鼠未见明显病理变化;急性排斥组大鼠肾脏呈急性排斥反应典型病理改变,可见交界性改变、灶状间质炎性细胞浸润、多灶状间质炎性细胞浸润、弥漫状间质炎性细胞浸润病理变化,其中急性排斥反应Ⅰ级2例、Ⅱ级2例、Ⅲ级5例、Ⅲb级6例。术后第7天急性排斥组血清肌酐[(123.50±8.06)μmol/L]、尿素氮[(7.40±0.75)mmol/L]水平高于非急性排斥组[(107.99±5.73)μmol/L、(6.04±0.84)mmol/L]和对照组[(49.28±6.85)μmol/L、(3.02±0.67)mmol/L](P<0.05);急性排斥组CD3~+T细胞比率[(50.68±7.59)%]、CD4~+T细胞比率[(35.81±5.49)%]、CD4~+/CD8~+(2.80±0.22)高于非急性排斥组[(41.97±9.01)%、(24.89±6.04)%、1.61±0.14]和对照组[(39.07±10.91)%、(21.74±6.02)%、1.43±0.14](P<0.05);急性排斥组CD8~+T细胞比率[(11.01±3.30)%]低于非急性排斥组[(15.39±4.07)%]和对照组[(15.61±4.81)%],CD4~+CD25~+调节性T细胞比率[(1.30±0.20)%]与Foxp3 mRNA[(0.33±0.08)×10~(-3)]水平低于非急性排斥组[(2.90±0.40)%、(1.02±0.21)×10~(-3)]和对照组[(4.97±0.50)%、(2.13±0.26)×10~(-3)](P<0.05)。结论外周血T细胞亚群参与调控肾移植术后急性排斥反应,急性排斥反应的发生可能与Foxp3 mRNA及CD4~+CD25~+调节性T细胞比率降低有关,Foxp3 mRNA及CD4~+CD25~+调节性T细胞可作为评估受体免疫状态、判断免疫耐受的参考指标。 Objective To investigate the expression of T lymphocyte subsets, CD4 ~ + CD25 ~ + regulatory T cells and forkhead transcription factor p3 (Foxp3) mRNA in acute rejection after renal transplantation in rats. significance. Methods Fifteen SD rats were used as control group. Fifteen SD rats were used as recipients. Fifteen SD rats were used as donors to establish non-acute rejection group. 15 SD rats were recipients and 15 Wistar rats Acute rejection group of non-syngeneic gene transplantation was established for donor. The levels of T lymphocyte subsets, CD4 ~ + CD25 ~ + regulatory T cells, Foxp3 mRNA, serum creatinine and blood urea nitrogen in peripheral blood of three groups of recipients were measured on the 7th day after renal transplantation. Histopathology was performed and renal allograft rejection was graded and compared. Results The histopathology of the kidneys showed no significant pathological changes in the control group. The rats in the non-acute rejection group showed borderline changes, small focal interstitial inflammatory cell infiltration, and 3 grade Ⅰ acute rejection reactions. The rest There were no obvious pathological changes in 8 recipient rats. Acute rejection rats showed typical pathological changes of acute rejection, showing borderline changes, focal interstitial inflammatory cell infiltration, multiple focal interstitial inflammatory cell infiltration, Diffuse interstitial inflammatory cell infiltration pathological changes, including acute rejection in grade Ⅰ in 2 cases, grade Ⅱ in 2 cases, grade Ⅲ in 5 cases, Ⅲ b in 6 cases. The levels of serum creatinine [(123.50 ± 8.06) μmol / L] and urea nitrogen [(7.40 ± 0.75) mmol / L] in the acute rejection group were higher than those in the non-acute rejection group [(107.99 ± 5.73) μmol / (6.04 ± 0.84) mmol / L] and control group (49.28 ± 6.85 μmol / L, 3.02 ± 0.67 mmol / L, P <0.05). The ratio of CD3 + T cells in acute rejection group was (50.68 ± (41.97 ± 9.01)%, (24.89 ± 6.04)%, CD4 ~ + T cell ratio (35.81 ± 5.49)%, CD4 ~ + / CD8 ~ ) And 1.61 ± 0.14 in the control group [(39.07 ± 10.91)% vs (21.74 ± 6.02)%, 1.43 ± 0.14], respectively %] Was lower than that of non-acute rejection group [(15.39 ± 4.07)%] and control group (15.61 ± 4.81%), and CD4 ~ + CD25 ~ + regulatory T cell ratio [(0.33 ± 0.08) × 10 (-3)] was lower than that of the non-acute rejection group (2.90 ± 0.40% vs 1.02 ± 0.21 × 10-3) and the control group (4.97 ± 0.50 )%, (2.13 ± 0.26) × 10 -3] (P <0.05). Conclusion The peripheral blood T lymphocyte subsets participate in the regulation of acute rejection after renal transplantation. The incidence of acute rejection may be related to the decrease of Foxp3 mRNA and the ratio of CD4 ~ + CD25 ~ + regulatory T cells. Foxp3 mRNA and CD4 ~ + CD25 + Regulatory T cells can be used as a measure of receptor immune status, to determine the immune tolerance of the reference index.
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