Chinese Journal of Dermatology ›› 2014, Vol. 47 ›› Issue (2): 99-103.

• Original articles • Previous Articles     Next Articles

Therapeutic efficacy and mechanism of total lymphoid irradiation with electron beam in MRL/lpr mouse model of lupus

  

  • Received:2013-04-01 Revised:2013-06-19 Online:2014-02-15 Published:2014-02-01
  • Contact: Zhiqi Song E-mail:szqdalian@163.com

Abstract: Ding Wen, Yu Zhan, Song Zhiqi. First Affiliated Hospital, Dalian Medical University, Dalian 116011, China Corresponding authors: Song Zhiqi, Email: szqdalian@yahoo.com; Yu Zhan, Email: yuzhan@yahoo.com 【Abstract】 Objective To evaluate the therapeutic efficacy of total lymphoid irradiation with electronic beam in MRL/lpr mouse model of lupus, and to assess the relationship between total lymphoid irradiation and regulatory T (Treg) cells. Methods Eighteen four-month-old MRL/lpr lupus mice were randomly divided into three groups with three female mice and three male mice in each group: negative control group treated with intraperitoneal sodium chloride physiological solution 0.5 ml once daily, radiotherapy group receiving total lymphoid irradiation with the electronic beam (2 Gy per day) five times a week, and dexamethasone group treated with intraperitoneal dexamethasone 1 mg/kg once daily for two consecutive weeks. Then, Coomassie brilliant blue method was used to quantify the 24-hour urinary protein, and enzyme-linked immunosorbent assay (ELISA) to measure the serum levels of antinuclear antibody (ANA) and anti-dsDNA antibody. All the mice were sacrificed, renal tissue was obtained and subjected to direct immunofluorescence assay for the observation of IgG deposits as well as periodic acid-Schiff staining for the evaluation of renal injury, and spleen tissue was isolated and subjected to flow cytometry for the determination of proportion of Treg cells in spleen cells. Data were processed using the SPSS 11.5 software. Statistical analysis was done with one-way analysis of variance. Results Significant differences were observed between the radiotherapy group and negative control group in 24-hour urinary protein level ((3.33 ± 0.17) vs. (3.97 ± 0.33) mg, P < 0.05), serum ANA antibody level ((275.12 ± 30.18) vs. (434.82 ± 36.63) U/ml, P < 0.05) and anti-dsDNA antibody level ((455.74 ± 43.38) vs.(956.78 ± 37.69) IU/ml, P < 0.05). The glomerular deposition of IgG antibody was obviously decreased with attenuated renal injury in the radiotherapy group and dexamethasone group compared with the negative control group, but no significant difference was noted between the radiotherapy group and dexamethasone group. The proportion of Treg cells in the radiotherapy group and dexamethasone group was significantly higher than that in the negative control group ((1.08 ± 0.52)% and (1.18 ± 0.60)% vs. (0.38 ± 0.14)%, both P < 0.05). Conclusions Total lymphoid irradiation with electronic beam can effectively reduce urine protein level, serum ANA and anti-dsDNA antibody level in MRL/lpr lupus mice, alleviate renal injury, likely by up-regulating the proportion of Treg cells in vivo.

Key words: Mice, inbred MRL lpr, Lupus erythematosus, systemic, T-lymphocytes, regulatory, Lymphatic irradiation